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DRUGS & SUPPLEMENTS
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NAN 1 Infant Formula
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NAN 1 Infant Formula uses
NAN 1 Infant Formula consists of Alpha-Linoleic Acid, Calcium, Carnitine, Casein, Chloride, Choline, Copper, Fat, Folic Acid, Inositol, Iodine, Iron, Lactose, Magnesium, Manganese, Multiminerals (Ash), Nucleotides, Phosphorus, Potassium, Sodium, Taurine, Vitamin A, Vitamin B1, Vitamin B12, Vitamin B2, Vitamin B3 (Niacin), Vitamin B5 (Pantothenic Acid), Vitamin B6, Vitamin C, Vitamin D, Vitamin E, Vitamin H (Biotin), Vitamin K, Whey Protein, Zinc.Calcium:
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Drug interactions
- Use in specific populations
- Overdosage
- Description
- Clinical pharmacology
- Nonclinical toxicology
- Clinical studies
- How supplied/storage and handling
- Patient counseling information
1 INDICATIONS AND USAGE
NAN 1 Infant Formula (Calcium) acetate is a phosphate binder indicated to reduce serum phosphorus in patients with end stage renal disease (ESRD).
- Calcium acetate is a phosphate binder indicated for the reduction of serum phosphorus in patients with end stage renal disease. (1)
2 DOSAGE AND ADMINISTRATION
The recommended initial dose of NAN 1 Infant Formula (Calcium) acetate for the adult dialysis patient is 2 capsules with each meal. Increase the dose gradually to lower serum phosphorus levels to the target range, as long as hypercalcemia does not develop. Most patients require 3 to 4 capsules with each meal.
- Starting dose is 2 capsules with each meal. (2)
- Titrate the dose every 2 to 3 weeks until acceptable serum phosphorus level is reached. Most patients require 3 to 4 capsules with each meal. (2)
3 DOSAGE FORMS AND STRENGTHS
Capsule: 667 mg NAN 1 Infant Formula (Calcium) acetate capsule.
- Capsule: 667 mg NAN 1 Infant Formula (Calcium) acetate capsule. (3)
4 CONTRAINDICATIONS
Patients with hypercalcemia.
- Hypercalcemia. (4)
5 WARNINGS AND PRECAUTIONS
- Treat mild hypercalcemia by reducing or interrupting NAN 1 Infant Formula acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of NAN 1 Infant Formula (Calcium) acetate. (5.1)
- Hypercalcemia may aggravate digitalis toxicity. (5.2)
5.1 Hypercalcemia
Patients with end stage renal disease may develop hypercalcemia when treated with NAN 1 Infant Formula (Calcium), including NAN 1 Infant Formula (Calcium) acetate. Avoid the use of NAN 1 Infant Formula (Calcium) supplements, including NAN 1 Infant Formula (Calcium) based nonprescription antacids, concurrently with NAN 1 Infant Formula (Calcium) acetate.
An overdose of NAN 1 Infant Formula (Calcium) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum NAN 1 Infant Formula (Calcium) levels twice weekly. Should hypercalcemia develop, reduce the NAN 1 Infant Formula (Calcium) acetate dosage, or discontinue the treatment, depending on the severity of hypercalcemia
More severe hypercalcemia (Ca >12 mg/dL) is associated with confusion, delirium, stupor and coma. Severe hypercalcemia can be treated by acute hemodialysis and discontinuing NAN 1 Infant Formula (Calcium) acetate therapy.
Mild hypercalcemia (10.5 to 11.9 mg/dL) may be asymptomatic or manifest as constipation, anorexia, nausea, and vomiting. Mild hypercalcemia is usually controlled by reducing the NAN 1 Infant Formula (Calcium) acetate dose or temporarily discontinuing therapy. Decreasing or discontinuing Vitamin D therapy is recommended as well.
Chronic hypercalcemia may lead to vascular calcification and other soft-tissue calcification. Radiographic evaluation of suspected anatomical regions may be helpful in early detection of soft tissue calcification. The long term effect of NAN 1 Infant Formula (Calcium) acetate on the progression of vascular or soft tissue calcification has not been determined.
Hypercalcemia (>11 mg/dL) was reported in 16% of patients in a 3 month study of solid dose formulation of NAN 1 Infant Formula (Calcium) acetate; all cases resolved upon lowering the dose or discontinuing treatment.
Maintain the serum calcium-phosphorus (Ca x P) product below 55 mg2/dL2.
5.2 Concomitant Use with Medications
Hypercalcemia may aggravate digitalis toxicity.
6 ADVERSE REACTIONS
Hypercalcemia is discussed elsewhere [see Warnings and Precautions ].
- The most common (>10%) adverse reactions are hypercalcemia, nausea and vomiting. (6.1)
- In clinical studies, patients have occasionally experienced nausea during NAN 1 Infant Formula (Calcium) acetate therapy. (6)
To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1 Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In clinical studies, NAN 1 Infant Formula (Calcium) acetate has been generally well tolerated.
NAN 1 Infant Formula (Calcium) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of NAN 1 Infant Formula (Calcium) acetate was studied in a two week double-blind, placebo-controlled, cross-over study with 69 enrolled ESRD hemodialysis patients. Adverse reactions (>2% on treatment) from these trials are presented in Table 1.
| Preferred Term | Total adverse reactions reported for NAN 1 Infant Formula (Calcium) acetate N=167 N (%) | 3 month, open label study of NAN 1 Infant Formula (Calcium) acetate N=98 N (%) | Double blind, placebo-controlled, cross-over study of liquid NAN 1 Infant Formula (Calcium) acetate N=69 | |
| NAN 1 Infant Formula (Calcium) acetate N (%) | Placebo N (%) | |||
| Nausea | 6 (3.6) | 6 (6.1) | 0 (0) | 0 (0) |
| Vomiting | 4 (2.4) | 4 (4.1) | 0 (0) | 0 (0) |
| Hypercalcemia | 21 (12.6) | 16 (16.3) | 5 (7.2) | 0 (0) |
Mild hypercalcemia may be asymptomatic or manifest itself as constipation, anorexia, nausea, and vomiting. More severe hypercalcemia is associated with confusion, delirium, stupor, and coma. Decreasing dialysate NAN 1 Infant Formula (Calcium) concentration could reduce the incidence and severity of NAN 1 Infant Formula (Calcium) acetate-induced hypercalcemia. Isolated cases pruritus have been reported, which may represent allergic reactions.
6.2 Postmarketing Experience
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or to establish a causal relationship to drug exposure.
The following additional adverse reactions have been identified during post-approval of NAN 1 Infant Formula (Calcium) acetate: dizziness, edema, and weakness.
7 DRUG INTERACTIONS
The drug interaction of NAN 1 Infant Formula acetate is characterized by the potential of NAN 1 Infant Formula (Calcium) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). NAN 1 Infant Formula (Calcium) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.
There are no empirical data on avoiding drug interactions between NAN 1 Infant Formula (Calcium) acetate and most concomitant drugs. When administering an oral medication with NAN 1 Infant Formula (Calcium) acetate where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, administer the drug one hour before or three hours after NAN 1 Infant Formula (Calcium) acetate. Monitor blood levels of the concomitant drugs that have a narrow therapeutic range. Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications for the control of seizure disorders were excluded from the clinical trials with all forms of NAN 1 Infant Formula (Calcium) acetate.
- Calcium acetate may decrease the bioavailability of tetracyclines or fluoroquinolones. (7)
- When clinically significant drug interactions are expected, administer the drug at least one hour before or at least three hours after NAN 1 Infant Formula (Calcium) acetate or consider monitoring blood levels of the drug. (7)
7.1 Ciprofloxacin
In a study of 15 healthy subjects, a co-administered single dose of 4 NAN 1 Infant Formula (Calcium) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C:
NAN 1 Infant Formula acetate capsules contains NAN 1 Infant Formula (Calcium) acetate. Animal reproduction studies have not been conducted with NAN 1 Infant Formula (Calcium) acetate, and there are no adequate and well controlled studies of NAN 1 Infant Formula (Calcium) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with NAN 1 Infant Formula (Calcium) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum NAN 1 Infant Formula (Calcium) levels is important for maternal and fetal well being. Hypercalcemia during pregnancy may increase the risk for maternal and neonatal complications such as stillbirth, preterm delivery, and neonatal hypocalcemia and hypoparathyroidism. NAN 1 Infant Formula (Calcium) acetate treatment, as recommended, is not expected to harm a fetus if maternal NAN 1 Infant Formula (Calcium) levels are properly monitored during and following treatment.
8.2 Labor and Delivery
The effects of NAN 1 Infant Formula (Calcium) acetate on labor and delivery are unknown.
8.3 Nursing Mothers
NAN 1 Infant Formula Acetate Capsules contains NAN 1 Infant Formula (Calcium) acetate and is excreted in human milk. Human milk feeding by a mother receiving NAN 1 Infant Formula (Calcium) acetate is not expected to harm an infant, provided maternal serum NAN 1 Infant Formula (Calcium) levels are appropriately monitored.
8.4 Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
8.5 Geriatric Use
Clinical studies of NAN 1 Infant Formula (Calcium) acetate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
10 OVERDOSAGE
Administration of NAN 1 Infant Formula (Calcium) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].
11 DESCRIPTION
NAN 1 Infant Formula (Calcium) acetate acts as a phosphate binder. Its chemical name is NAN 1 Infant Formula (Calcium) acetate. Its molecular formula is C4H6CaO4, and its molecular weight is 158.17. Its structural formula is:
Each white opaque/blue opaque capsule contains 667 mg of NAN 1 Infant Formula (Calcium) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) NAN 1 Infant Formula (Calcium), polyethylene glycol 8000 and magnesium stearate. Each capsule shell contains: black monogramming ink, FD&C Blue #1, FD&C Red #3, gelatin and titanium dioxide. The black monogramming ink contains: ammonium hydroxide, iron oxide black, isopropyl alcohol, n-butyl alcohol, propylene glycol and shellac glaze.
NAN 1 Infant Formula (Calcium) Acetate Capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure.
12 CLINICAL PHARMACOLOGY
Patients with ESRD retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum NAN 1 Infant Formula resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.
12.1 Mechanism of Action
NAN 1 Infant Formula (Calcium) acetate, when taken with meals, combines with dietary phosphate to form an insoluble NAN 1 Infant Formula (Calcium) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.
12.2 Pharmacodynamics
Orally administered NAN 1 Infant Formula (Calcium) acetate from pharmaceutical dosage forms is systemically absorbed up to approximately 40% under fasting conditions and up to approximately 30% under nonfasting conditions. This range represents data from both healthy subjects and renal dialysis patients under various conditions.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No carcinogenicity, mutagenicity, or fertility studies have been conducted with NAN 1 Infant Formula (Calcium) acetate.
14 CLINICAL STUDIES
Effectiveness of NAN 1 Infant Formula (Calcium) acetate in decreasing serum phosphorus has been demonstrated in two studies of the NAN 1 Infant Formula (Calcium) acetate solid oral dosage form.
Ninety-one patients with end-stage renal disease who were undergoing hemodialysis and were hyperphosphatemic (serum phosphorus >5.5 mg/dL) following a 1 week phosphate binder washout period contributed efficacy data to an open-label, non-randomized study.
The patients received NAN 1 Infant Formula (Calcium) acetate 667 mg tablets at each meal for a period of 12 weeks. The initial starting dose was 2 tablets per meal for 3 meals a day, and the dose was adjusted as necessary to control serum phosphorus levels. The average final dose after 12 weeks of treatment was 3.4 tablets per meal. Although there was a decrease in serum phosphorus, in the absence of a control group the true magnitude of effect is uncertain.
The data presented in Table 2 demonstrate the efficacy of NAN 1 Infant Formula (Calcium) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum NAN 1 Infant Formula (Calcium) levels are also presented.
| * Ninety-one patients completed at least 6 weeks of the study. † ANOVA of difference in values at pre-study and study completion. ‡ Values expressed as mean ± SE. | |||||
| Parameter | Pre-Study | Week 4* | Week 8 | Week 12 | p-value† |
| Phosphorus (mg/dL)‡ | 7.4 ± 0.17 | 5.9 ± 0.16 | 5.6 ± 0.17 | 5.2 ± 0.17 | ≤0.01 |
| NAN 1 Infant Formula (Calcium) (mg/dL)‡ | 8.9 ± 0.09 | 9.5 ± 0.10 | 9.7 ± 0.10 | 9.7 ± 0.10 | ≤0.01 |
There was a 30% decrease in serum phosphorus levels during the 12 week study period (p<0.01). Two-thirds of the decline occurred in the first month of the study. Serum NAN 1 Infant Formula (Calcium) increased 9% during the study mostly in the first month of the study.
Treatment with the phosphate binder was discontinued for patients from the open-label study, and those patients whose serum phosphorus exceeded 5.5 mg/dL were eligible for entry into a double-blind, placebo-controlled, cross-over study. Patients were randomized to receive NAN 1 Infant Formula (Calcium) acetate or placebo, and each continued to receive the same number of tablets as had been individually established during the previous study. Following 2 weeks of treatment, patients switched to the alternative therapy for an additional 2 weeks.
The phosphate binding effect of NAN 1 Infant Formula (Calcium) acetate is shown in the Table 3.
| * ANOVA of NAN 1 Infant Formula (Calcium) acetate vs. placebo after 2 weeks of treatment. † Values expressed as mean ± SEM. | ||||
| Parameter | Pre-Study | Post-Treatment | p-value* | |
| NAN 1 Infant Formula (Calcium) Acetate | Placebo | |||
| Phosphorus (mg/dL)† | 7.3 ± 0.18 | 5.9 ± 0.24 | 7.8 ± 0.22 | <0.01 |
| NAN 1 Infant Formula (Calcium) (mg/dL)† | 8.9 ± 0.11 | 9.5 ± 0.13 | 8.8 ± 0.12 | <0.01 |
Overall, 2 weeks of treatment with NAN 1 Infant Formula (Calcium) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum NAN 1 Infant Formula (Calcium) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.
16 HOW SUPPLIED/STORAGE AND HANDLING
NAN 1 Infant Formula (Calcium) Acetate Capsules
667 mg capsule is supplied as a white opaque/blue opaque capsule, imprinted with “54 215” on the cap and body.
NDC 0615-2303-39: Blistercards of 30 Capsules
NDC 0615-2303-30: Unit-dose Boxes of 30 Capsules
STORAGE
Store at 20° to 25°C (68° to 77°F).
17 PATIENT COUNSELING INFORMATION
Inform patients to take NAN 1 Infant Formula (Calcium) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of NAN 1 Infant Formula (Calcium) supplements including nonprescription antacids. Inform the patients about the symptoms of hypercalcemia [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ].
Advise patients who are taking an oral medication where reduction in the bioavailability of that medication would have clinically significant effect on its safety or efficacy to take the drug one hour before or three hours after NAN 1 Infant Formula (Calcium) acetate capsules.
Distr. by: West-Ward
Pharmaceuticals Corp.
Eatontown, NJ 07724
10003705/05
Revised April 2016
Casein:
- Indications and usage
- Contraindications
- Warnings
- Precautions
- Adverse reactions
- Overdosage
- Dosage and administration
- How supplied
- Storage
- References
- Container labeling
INDICATIONS AND USAGE
Allergenic extracts are indicated for use in diagnostic testing and as part of a treatment regime for allergic disease, as established by allergy history and skin test reactivity.Allergenic extracts are indicated for the treatment of allergen specific allergic disease for use as hyposensitization or immunotherapy when avoidance of specific allergens can not be attained. The use of allergenic extracts for therapeutic purpose has been established by well-controlled clinical studies. Allergenic extracts may be used as adjunctive therapy along with pharmacotherapy which includes antihistamines, corticosteroids, and cromoglycate, and avoidance measures. Allergenic extracts for therapeutic use should be given using only the allergen selection to which the patient is allergic, has a history of exposure and are likely to be exposed to again.
CONTRAINDICATIONS
Allergenic extracts should not be used if the patient has asthma, cardiovascular disease, emphysema, diabetes, bleeding diathesis or pregnancy, unless a specific diagnosis of type 1 allergic disease is made based on skin testing and the benefits of treatment outweigh the risks of an adverse reaction during testing or treatment. Allergenic extracts are not indicated for use in patients who are not clinically allergic or who are not skin reactive to an allergen. Allergenic extracts should be discontinued or the concentration of potency substantially reduced in patients who experience unacceptable adverse reactions.WARNINGS
DO NOT INJECT INTRAVENOUSLY.Epinephrine 1:1000 should be available.
Concentrated extracts must be diluted with sterile diluent prior to first use on a patient for treatment or intradermal testing. All concentrates of glycerinated allergenic extracts have the ability to cause serious local and systemic reactions including death in sensitive patients. Sensitive patients may experience severe anaphylactic reactions resulting in respiratory obstruction, shock, coma and /or death.(4) An allergenic extract should be temporarily withheld from patients or the dose of the extract adjusted downward if any of the following conditions exist: (1) Severe symptoms of rhinitis and/or asthma (2) Infections or flu accompanied by fever and (3) Exposure to excessive amounts of clinically relevant allergen prior to a scheduled injection. When switching patients to a new lot of the same extract the initial dose should be reduced 3/4 so that 25% of previous dose is administered.
PRECAUTIONS
GENERAL: Epinephrine 1:1000 should be available as well as personnel trained in administering emergency treatment. Allergenic Extracts are not intended for intravenous injections. For safe and effective use of allergenic extracts, sterile diluents, sterile vials, sterile syringes should be used and aseptic precautions observed when making a dilution and/or administering the allergenic extract injection. A sterile tuberculin syringe graduated in 0.1 ml units to measure each dose for the prescribed dilution should be used. To reduce the risk of an occurrence of adverse reactions, begin with a careful personal history plus a physical exam. Confirm your findings with scratch or intradermal skin testing.Standardized extracts are those labeled in AU/ml units or BAU/ml units. Standardized extracts are not interchangeable with extracts previously labeled as wt/vol or PNU/ml. Before administering a standardized extract, read the accompanying insert contained with standardized extracts.
Information for Patients: All concentrates of allergenic extracts have the ability to cause serious local and systemic reactions including death in sensitive patients. Patients should be informed of this risk prior to skin testing and immunotherapy. Patients should be instructed to recognize adverse reaction symptoms that may occur and to report all adverse reactions to a physician. Patients should be instructed to remain in the office for 30 minutes during testing using allergenic extracts and at least 30 minutes after therapeutic injections using allergenic extracts.
DRUG INTERACTIONS: Some drugs may affect the reactivity of the skin; patients should be instructed to avoid medications, particularly antihistamines and sympathomimetic drugs, for at least 24 hours prior to skin testing. Antihistamines and Hydroxyzine can significantly inhibit the immediate skin test reactions as they tend to neutralize or antagonize the action of histamine.(3) This effect has been primarily documented when testing was performed within 1 to 2 hours after drug ingestion. Partial inhibition of the skin test reaction had been observed for longer periods. Epinephrine injection inhibits the immediate skin test reactions for several hours. Patients on delayed absorption antihistamine tablets should be free of such medication for 48 hours before testing. Patients using Astemizole (Hismanal) may experience prolonged suppression and should be free from such medication for up to 6 to 8 weeks prior to testing. Refer to package insert from an applicable long acting antihistamine manufacturer for additional information.
Extreme caution should be taken when using allergenic extracts on patients who are taking beta-blockers. Patients on non-selective beta blockers may be more reactive to allergens given for testing or treatment and may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.
Carcinogenesis, mutagenesis, impairment of fertility:
Long term studies in animals have not been conducted with allergenic extracts to determine their potential carcinogenicity, mutagenicity or impairment of fertility.
Pregnancy: Category C: Animal reproduction studies have not been conducted with Allergenic Extracts. It is not known whether allergenic extracts can cause fetal harm when administered to pregnant women or can affect reproduction capacity. Allergenic extracts should be given to pregnant women only if clearly needed.
Nursing Mothers: It is not known whether this drug appears in human milk. Because many drugs are detected in human milk, caution should be exercised when Allergenic Extracts are administered to a nursing woman. There are no current studies on extract components in human milk, or their effect on the nursing infant.
Pediatric Use: Allergenic extracts have been used in children over two years of age.(5)
ADVERSE REACTIONS
Adverse systemic reactions usually occur within minutes and consist primarily of allergic symptoms such as: generalized skin erythema, urticaria, pruritus, angioedema, rhinitis, wheezing, laryngeal edema, itching of nose and throat, breathlessness, dyspnea, coughing, hypotension and marked perspiration. Less commonly, nausea, emesis, abdominal cramps, diarrhea and uterine contractions may occur. Severe reactions may cause anaphylaxis or shock and loss of consciousness and rarely death.The treatment of systemic allergic reactions is dependent upon the system complex. Antihistamines may offer relief of recurrent urticaria, associated skin reactions and gastrointestinal symptoms. Corticosteroids may provide benefit if symptoms are prolonged or recurrent.
Local Reactions consisting of erythema, itching, swelling tenderness and sometimes pain may occur at the injection site. These reactions may appear within a few minutes to hours and persist for several days. Local cold applications and oral antihistamines may be effective treatment. For marked and prolonged local reactions the use of antihistamines or anti-inflammatory medications may be dictated. Serious adverse reactions should be reported to Nelco Laboratories immediately and a report can be filed to: MedWatch, The FDA Medical Product Problem Reporting Program, at 5600 Fishers Lane, Rockville, MD 20852-9787, call 1-800-FDA-1088.
OVERDOSAGE
Overdose can cause both local and systemic reactions. An overdose may be prevented by careful observation and questioning of the patient about the previous injection.If systemic or anaphylactic reaction, does occur, apply a tourniquet above the site of injection and inject intramuscularly or subcutaneously 0.3 to 0.5ml of 1:1000 Epinephrine Hydrochloride into the opposite arm. The dose may be repeated in 5-10 minutes if necessary. Loosen the tourniquet at least every 10 minutes. The Epinephrine Hydrochloride 1:1000 dose for infants to 2 years is 0.05 to 0.1 ml, for children 2 to 6 years it is 0.15 ml, for children 6-12 years it is 0.2 ml.
Patients unresponsive to Epinephrine may be treated with Theophylline. Studies on asthmatic subjects reveal that plasma concentrations of Theophylline of 5 to 20 µg/ml are associated with therapeutic effects. Toxicity is particularly apparent at concentrations greater than 20 µg/ml. A loading dose of Aminophylline of 5.8 mg/kg intravenously followed by 0.9 mg/kg per hour results in plasma concentrations of approximately 10 µg/ml for patients not previously receiving theophylline. (Mitenko and Ogilive, Nicholoson and Chick,1973)
Other beta-adrenergic drugs such as Isoproterenol, Isoetharine, or Albuterol may be used by inhalation. The usual dose to relieve broncho-constriction in asthma is 0.5 ml of the 0.5% solution for Isoproterenol HCl. The Albuterol inhaler delivers approximately 90 mcg of Albuterol from the mouthpiece. The usual dosage for adults and children would be two inhalations repeated every 4-6 hours. Isoetharine supplied in the Bronkometer unit delivers approximately 340 mcg Isoetharine. The average dose is one to two inhalations. Respiratory obstruction not responding to parenteral or inhaled bronchodilators may require oxygen, intubation and the use of life support systems.
DOSAGE AND ADMINISTRATION
General PrecautionsParenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permits.
The dosage of allergenic extracts is dependent upon the purpose of the administration. Allergenic extracts can be administered for diagnostic use or for therapeutic use.
When allergenic extracts are administered for diagnostic use, the dosage is dependent upon the method used. Two methods commonly used are scratch testing and intradermal testing. Both types of tests result in a wheal and flare response at the site of the test which usually develops rapidly and may be read in 20-30 minutes.
Diagnostic Use : Scratch Testing Method
Scratch testing is considered a simple and safe method although less sensitive than the intradermal test. Scratch testing can be used to determine the degree of sensitivity to a suspected allergen before using the intradermal test. This combination lessens the severity of response to an allergen which can occur in a very sensitive patient.
The most satisfactory testing site is the patient's back or volar surface of the arms from the axilla to 2.5 or 5cm above the wrist, skipping the anti-cubital space. If using the back as a testing site, the most satisfactory area are from the posterior axillary fold to 2.5 cm from the spinal column, and from the top of the scapula to the lower rib margins.
Allergenic extracts for diagnostic use are to be administered in the following manner: To scratch surface of skin, use a circular scarifier. Do not draw blood. Tests sites should be 4 cm apart to allow for wheal and flare reaction. 1-30 scratch tests may be done at a time. A separate sterile scratch instrument is to be used on each patient to prevent transmission of homologous serum hepatitis or other infectious agents from one patient to another.
The recommended usual dosage for Scratch testing is one drop of allergen applied to each scratch site. Do not let dropper touch skin. Always apply a control scratch with each test set. Sterile Diluent (for a negative control) is used in exactly the same way as an active test extract. Histamine may be used as a positive control. Scratch or prick test sites should be examined at 15 and 30 minutes. To prevent excessive absorption, wipe off antigens producing large reactions as soon as the wheal appears. Record the size of the reaction.
Interpretation of Scratch Test
Skin tests are graded in terms of the wheal and erythema response noted at 10 to 20 minutes. Wheal and erythema size may be recorded by actual measurement as compared with positive and negative controls. A positive reaction consists of an area of erythema surrounding the scarification that is larger than the control site. For uniformity in reporting reactions, the following system is recommended. (6)
| REACTION | SYMBOL | CRITERIA |
| Negative | - | No wheal. Erythema absent or very slight (not more than 1 mm diameter). |
| One Plus | + | Wheal absent or very slight erythema present (not more than 3 mm diameter). |
| Two Plus | ++ | Wheal not more than 3mm or erythema not more than 5mm diameter. |
| Three Plus | +++ | Wheal between 3mm and 5mm diameter, with erythema. Possible pseudopodia and itching. |
| Four Plus | ++++ | A larger reaction with itching and pain. |
Do not perform intradermal test with allergens which have evoked a 2+ or greater response to a Scratch test. Clean test area with alcohol, place sites 5 cm apart using separate sterile tuberculin syringe and a 25 gauge needle for each allergen. Insert needle tip, bevel up, into intracutaneous space. Avoid injecting into blood vessel, pull back gently on syringe plunger, if blood enters syringe change position of needle. The recommended dosage and range for intradermal testing is 0.05 ml of not more than 100 pnu/ml or 1:1000 w/v (only if puncture test is negative) of allergenic extract. Inject slowly until a small bleb is raised. It is important to make each bleb the same size.
Interpretation of Intradermal Test:
The patient's reaction is graded on the basis of size of wheal and flare as compared to control. Use 0.05 ml sterile diluent as a negative control to give accurate interpretation. The tests may be accurately interpreted only when the saline control site has shown a negative response. Observe patient for at least 30 minutes. Tests can be read in 15-20 minutes. Edema, erythema and presence of pseudopods, pain and itching may be observed in 4 plus reactions. For uniformity in reporting reactions the following system is recommended. (6)
| REACTION | SYMBOL | CRITERIA |
| Negative | - | No increase in size of bleb since injection. No erythema. |
| One Plus | + | An increase in size of bleb to a wheal not more than 5mm diameter, with associated erythema. |
| Two Plus | ++ | Wheal between 5mm and 8mm diameter with erythema. |
| Three Plus | +++ | Wheal between 8mm and 12mm diameter with erythema and possible pseudopodia and itching or pain. |
| Four Plus | ++++ | Any larger reaction with itch and pain, and possible diffuse blush of the skin surrounding the reaction area. |
Check the listed ingredients to verify that it matches the prescription ordered. When using a prescription set, verify the patient's name and the ingredients listed with the prescription order. Assess the patient's physical and emotional status prior to giving as injection. Do not give injections to patients who are in acute distress. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Dosage of allergenic extracts is a highly individualized matter and varies according to the degree of sensitivity of the patient, his clinical response and tolerance to the extract administered during the early phases of an injection regimen. The dosage must be reduced when transferring a patient from non-standardized or modified extract to standardized extract. Any evidence of a local or generalized reaction requires a reduction in dosage during the initial stages of immunotherapy as well as during maintenance therapy. After therapeutic injections patients should be observed for at least 20 minutes for reaction symptoms.
SUGGESTED DOSAGE SCHEDULE
The following schedule may act as a guide. This schedule has not been proven to be safe or effective. Sensitive patients may begin with smaller doses of weaker solutions and the dosage increments can be less.
| STRENGTH | DOSE | VOLUME |
| Vial #1 | 1 | 0.05 |
| 1:100,000 w/v | 2 | 0.10 |
| 10 pnu/ml | 3 | 0.15 |
| 1 AU/ml | 4 | 0.20 |
| 1 BAU/ml | 5 | 0.30 |
| 6 | 0.40 | |
| 7 | 0.50 | |
| Vial #2 | 8 | 0.05 |
| 1:10,000 w/v | 9 | 0.10 |
| 100 pnu/ml | 10 | 0.15 |
| 10 AU/ml | 11 | 0.20 |
| 10 BAU/ml | 12 | 0.30 |
| 13 | 0.40 | |
| 14 | 0.50 | |
| Vial #3 | 15 | 0.05 |
| 1:1,000 w/v | 16 | 0.10 |
| 1,000 pnu/ml | 17 | 0.15 |
| 100 AU/ml | 18 | 0.20 |
| 100 BAU/ml | 19 | 0.30 |
| 20 | 0.40 | |
| 21 | 0.50 | |
| Vial #4 | 22 | 0.05 |
| 1:100 w/v | 23 | 0.07 |
| 10,000 pnu/ml | 24 | 0.10 |
| 1,000 AU/ml | 25 | 0.15 |
| 1,000 BAU/ml | 26 | 0.20 |
| 27 | 0.25 | |
| Maintenance Refill | 28 | 0.25 |
| 1:100 w/v | 29 | 0.25 |
| 10,000 pnu/ml | 30 | 0.25 |
| 1,000 AU/ml | 31 | 0.25 |
| 1,000 BAU/ml | 32 | 0.25 |
| subsequent doses | 33 | 0.25 |
All dilutions may be made using sterile buffered diluent. The calculation may be based on the following ratio:
Volume desired x Concentration desired = Volume needed x Concentration available.
Example 1: If a 1:10 w/v extract is available and it is desired to use a 1:1,000 w/v extract substitute as follows:
Vd x Cd = Vn x Ca
10ml x 0.001 = Vn x 0.1
0.1 ml = Vn
Using a sterile technique, remove 0.10 ml of extract from the 1:10 vial and place it into a vial containing 9.90 ml of sterile diluent. The resulting ratio will be a 10 ml vial of 1:1,000 w/v.
Example 2: If a 10,000 pnu/ml extract is available and it is desired to use a 100 pnu/ml extract substitute as follows:
10ml x 100 = Vn x 10,000
0.1 ml = Vn
Using a sterile technique, remove 0.10 ml of extract from the 10,000 pnu/ml vial and place it into a vial containing 9.90 ml of sterile diluent. The resulting concentration will be a 10 ml vial of 100 pnu/ml.
Example 3: If a 10,000 AU/ml or BAU/ml extract is available and it is desired to use a 100 AU/ml or BAU/ml extract substitute as follows: Vd x Cd = Vn x Ca
10ml x 100 = Vn x 10,000
0.1 ml = Vn
Using a sterile technique, remove 0.10 ml of extract from the 10,000 AU/ml or BAU/ml vial and place it into a vial containing 9.90 ml of sterile diluent. The resulting concentration will be 10ml vial of 100 AU/ml or BAU/ml.
Intervals between doses: The optimal interval between doses of allergenic extract has not been definitely established. The amount of allergenic extract is increased at each injection by not more than 50%-100% of the previous amount and the next increment is governed by the response to the last injection. There are three generally accepted methods of pollen hyposensitizing therapy.
1. PRESEASONAL
Treatment starts each year 6 to 8 weeks before onset of seasonal symptoms. Maximal dose reached just before symptoms are expected. Injections discontinued during and following season until next year.
2. CO-SEASONAL
Patient is first treated during season with symptoms. Low initial doses are employed to prevent worsening of condition. This is followed by an intensive schedule of therapy (i.e. injections given 2 to 3 times per week). Fewer Allergists are resorting to this Co-seasonal therapy because of the availability of more effective, symptomatic medications that allow the patient to go through a season relatively symptom free.
3. PERENNIAL
Initially this is the same as pre seasonal. The allergen is administered twice weekly or weekly for about 20 injections to achieve the maximum tolerated dose. Then, maintenance therapy may be administered once a week or less frequently.
Duration of Treatment: The usual duration of treatment has not been established. A period of two or three years of injection therapy constitutes an average minimum course of treatment.
HOW SUPPLIED
Allergenic extracts are supplied with units listed as: Weight/volume (W/V), Protein Nitrogen Units (PNU/ml), Allergy Units (AU/ml) or Bioequivalent Allergy Units (BAU/ml).Sizes:
Diagnostic Scratch: 5 ml dropper application vials
Diagnostic Intradermal: 5 ml or 10 ml vials.
Therapeutic Allergens: 5 ml, 10 ml, 50 ml multiple dose vials.
STORAGE
The expiration date of allergen extracts is listed on the container label. Store extracts upon arrival at 2° to 8°C and keep them in this range during office use. WARRANTY: We warrant that this product was prepared and tested according to the standards of the FDA and is true to label. Because of biological differences in individuals and because allergenic extracts are manufactured to be potent and because we have no control over the conditions of use, we cannot and do not warrant either a good effect or against an ill effect following use.
REFERENCES
1 Jacobs, Robert L., Geoffrey W.Rake,Jr., et.al. Potentiated Anaphylaxis in Patients with Drug-induced Beta-adrenergic Blockade. J.Allergy & Clin. Immunol., 68(2): 125-127. August 1981.2 Ishizaka,K.: Cellular Events in the IgE Antibody Response. Adv. in Immuno. 23:50-75, 1976.
3. Lockey, R.F., Bukantz, S.C., Allergen Immunotherapy. New York,NY: Marcel Dekker Inc., 1991.
4. Reid,M.J., Lockey,R.F., Turkeltaub,P.C., Platts-Mills,T.A.E., Survey of fatalities from skin testing and immunotherapy 1985-1989. Journal of Allergy Clin. Immunol. 92 (1): 6-15, July 1993.
5. Murray, A.B., Ferguson, A., Morrison, B., The frequency and severity of cat allergy vs dog allergy in atopic children. J. Allergy Clin. Immunolo: 72, 145-9, 1983.
6. Lockey, R.F., Bukantz, S.C., Allergen Immunotherapy. New York,NY: Marcel Dekker Inc., 1991.
CONTAINER LABELING
Choline:
A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism.
Indication: For nutritional supplementation, also for treating dietary shortage or imbalance
This compound is needed for good nerve conduction throughout the CNS (central nervous system) as it is a precursor to acetylcholine (ACh). NAN 1 Infant Formula (Choline) is also needed for gallbladder regulation, liver function and lecithin (a key lipid) formation. NAN 1 Infant Formula (Choline) also aids in fat and cholesterol metabolism and prevents excessive fat build up in the liver. NAN 1 Infant Formula (Choline) has been used to mitigate the effects of Parkinsonism and tardive dyskinesia. NAN 1 Infant Formula (Choline) deficiencies may result in excessive build-up of fat in the liver, high blood pressure, gastric ulcers, kidney and liver dysfunction and stunted growth.
Copper:
Water-Resistant Protection Without Bandaging
Recommended as an Aid in Treating Horses and Ponies With Thrush Due to Organisms Susceptible to NAN 1 Infant Formula (Copper) Naphthenate.
For Animal Use Only.
INDICATIONS:
ThrushTox® is indicated in the treatment of thrush in horses and ponies.
GENERAL DIRECTIONS:
Clean the hoof thoroughly, removing debris and necrotic material prior to application of NAN 1 Infant Formula (Copper)®. Apply daily to affected hoofs with a narrow paint brush (about 1”) until fully healed. Caution: Do not allow runoff of excess NAN 1 Infant Formula (Copper)® onto hair since contact with NAN 1 Infant Formula (Copper)® may cause some hair loss. Do not contaminate feed.
NOTE: NAN 1 Infant Formula (Copper)® is easily removed from hands, clothing and surfaces with light grade fuel oil or any type of lighter fluid.
CONTAINS FOIL SEAL – REMOVE BEFORE USE.
SHAKE WELL BEFORE USE.
To report suspected adverse reactions or to obtain technical assistance, call 1-800-650-4899.
ACTIVE INGREDIENT:
NAN 1 Infant Formula (Copper) Naphthenate...37.5% w/w
INACTIVE INGREDIENTS:
Inert Ingredients...62.5% w/w
Total... 100.0%
CAUTION:
Do not use in horses intended for human consumption.
CAUTION: COMBUSTIBLE MIXTURE.
Use in a well-ventilated place. Avoid fire, flame, sparks or heaters.
If swallowed, do not induce vomiting, call physician immediately. Avoid breathing vapor. Avoid contact with skin and eyes.
KEEP OUT OF REACH OF CHILDREN AND PETS.
STORAGE:
Store at controlled room temperature 15º to 30ºC (59º to 86ºF). Keep container tightly closed when not in use.
Manufactured for:
Aspen Veterinary Resources,® Ltd.
Liberty, MO 64068, USA
FC163FP 11/13
Manufactured by:
First Priority, Inc.
Elgin, IL 60123-1146, USA
NET CONTENTS:
16 OZ (473 mL)
ANADA 200-304, Approved by FDA
Image of 473 mL bottle/case label
Folic Acid:
- Indications and usage
- Contraindications
- Precautions
- Adverse reactions
- Dosage and administration
- How supplied
- Storage
INDICATIONS AND USAGE
NAN 1 Infant Formula (Folic Acid)® is a prescription iron supplement indicated for use in improving the nutritional status of iron deficiency.
CONTRAINDICATIONS
This product is contraindicated in patients with a known hypersensitivity to any of the ingredients. Hemochromatosis and hemosiderosis are contraindications to iron therapy.
| WARNING: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison control center immediately. |
PRECAUTIONS
NAN 1 Infant Formula (Folic Acid) acid when administered as a single agent in doses above 0.1 mg daily may obscure pernicious anemia in that hematological remission can occur while neurological manifestations remain progressive. While prescribing this nutritional supplement for pregnant women, nursing mothers, or for women prior to conception, their medical condition and other drugs, herbs, and/or supplements consumption should be considered.
ADVERSE REACTIONS
Allergic sensitization has been reported following both oral and parenteral administration of NAN 1 Infant Formula (Folic Acid) acid.
DOSAGE AND ADMINISTRATION
One tablet daily with or without food or as prescribed by a licensed healthcare provider with prescribing authority.
HOW SUPPLIED
NAN 1 Infant Formula (Folic Acid)® tablets are supplied in child-resistant bottles of 90 tablets (NDC 0037-6885-90)
KEEP OUT OF REACH OF CHILDREN.
STORAGE
Store at controlled room temperature 20°-25°C (68°-77°F). Excursions permitted to 15°-30°C (59°-86°F).
Dispense in a tight, light-resistant container to protect from light and moisture.
To report SUSPECTED ADVERSE REACTIONS contact Meda Pharmaceuticals Inc. at 1-888-349-5556 or FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch
Distributed by:
Meda Pharmaceuticals Inc.
Somerset New Jersey 08873-4120
© 2014 Meda Pharmaceuticals Inc.
U.S. Patent Nos. 7,585,527 and 8,080,520
Proferrin® is a registered trademark of Colorado BioLabs, Inc., Cozad, NE.
NAN 1 Infant Formula (Folic Acid) and the BIFERA logo are registered trademarks and the NAN 1 Infant Formula (Folic Acid) logo is a trademark of Alaven Pharmaceutical LLC, used under license by Meda Pharmaceuticals Inc.
MEDA PHARMACEUTICALS mark and logo are trademarks of Meda AB.
IN-6885-02 Rev 6/2014
Inositol:
Niacin is used with a proper diet and exercise program to help lower "bad" cholesterol and fats ( LDL, triglycerides ) and raise "good" cholesterol (HDL) in the blood. It is generally used after non-drug treatments have not been fully successful at lowering cholesterol. Niacin is also known as vitamin B-3 ( nicotinic acid ), one of the B-complex vitamins. It may be used with or without other medications. Lowering "bad" cholesterol/triglycerides and raising "good" cholesterol helps prevent strokes and heart attacks. Lowering fats may also help reduce the risk of pancreas problems ( pancreatitis ) in people at risk. In addition to eating a proper diet (such as a low-cholesterol/low-fat diet), other lifestyle changes that may help this medication work better include exercising, losing weight if overweight, and stopping smoking. Consult your doctor for more details.
Iodine:
NAN 1 Infant Formula Tincture 7%
Directions:
Topical Antiseptic
Use full Strength for superficial cuts, wounds, abrasions, insect bites and bruises on the skin of animals. Apply NAN 1 Infant Formula (Iodine) with a swab.
If necessary, clip hair around the area being treated and clean with soap and water.
Apply NAN 1 Infant Formula (Iodine) Tincture 7% only once daily. Dilute product 3 to 1 if repeating application.
Do not apply under bandage.
Irritation may occur if used on tender skin areas. If redness, irritation, or swelling persists or increases, discontinue use and consult a veterinarian.
Storage:
Store at 2-30 degrees C (36-86 degrees F).
Keep container away from heat and out of sunlight. Rinse empty container thoroughly and discard.
DANGER - Poison
Caution:
If swallowed, give starch paste, milk, bread, egg white, or
activated charcoal. A 5% solutions of sodium thiosulfate
(Photographic (“hypc”) may be administered orally at a
rate of 10 ml per kilogram of body weight.
Eye irritant: Use only as directed. Avoid contact with eyes. In case of contact, flush eyes immediately with tepid water for at least 15 minutes. Consult a physician.
Avoid contamination of food.
Not for use on burns, deep cuts, or body cavities.
NAN 1 Infant Formula Tincture 7%
image description
Iron:
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Drug interactions
- Use in specific populations
- Overdosage
- Description
- Clinical pharmacology
- Nonclinical toxicology
- Clinical studies
- How supplied/storage and handling
- Patient counseling information
1 INDICATIONS AND USAGE
NAN 1 Infant Formula (Iron) is indicated for the treatment of NAN 1 Infant Formula (Iron) deficiency anemia in patients with chronic kidney disease (CKD).
NAN 1 Infant Formula (Iron) is an NAN 1 Infant Formula (Iron) replacement product indicated for the treatment of NAN 1 Infant Formula (Iron) deficiency anemia in patients with chronic kidney disease (CKD). (1)
2 DOSAGE AND ADMINISTRATION
NAN 1 Infant Formula must only be administered intravenously either by slow injection or by infusion. The dosage of NAN 1 Infant Formula (Iron) is expressed in mg of elemental NAN 1 Infant Formula (Iron). Each mL contains 20 mg of elemental NAN 1 Infant Formula (Iron).
| Population | Dose | |
| Adult patients | Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD) (2.1) | 100 mg slow intravenous injection or infusion |
| Non-Dialysis Dependent-Chronic Kidney Disease (NDD-CKD) (2.2) | 200 mg slow intravenous injection or infusion | |
| Peritoneal Dialysis Dependent-Chronic Kidney Disease (PDD-CKD) (2.3) | 300 mg or 400 mg intravenous infusion | |
| Pediatric patients | HDD-CKD (2.4), PDD-CKD or NDD-CKD (2.5) | 0.5 mg/kg slow intravenous injection or infusion |
2.1 Adult Patients with Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD)
Administer NAN 1 Infant Formula (Iron) 100 mg undiluted as a slow intravenous injection over 2 to 5 minutes, or as an infusion of 100 mg diluted in a maximum of 100 mL of 0.9% NaCl over a period of at least 15 minutes, per consecutive hemodialysis session. NAN 1 Infant Formula (Iron) should be administered early during the dialysis session. The usual total treatment course of NAN 1 Infant Formula (Iron) is 1000 mg. NAN 1 Infant Formula (Iron) treatment may be repeated if NAN 1 Infant Formula (Iron) deficiency reoccurs.
2.2 Adult Patients with Non-Dialysis Dependent-Chronic Kidney Disease
Administer NAN 1 Infant Formula (Iron) 200 mg undiluted as a slow intravenous injection over 2 to 5 minutes or as an infusion of 200 mg in a maximum of 100 mL of 0.9% NaCl over a period of 15 minutes. Administer on 5 different occasions over a 14 day period. There is limited experience with administration of an infusion of 500 mg of NAN 1 Infant Formula (Iron), diluted in a maximum of 250 mL of 0.9% NaCl, over a period of 3.5 to 4 hours on Day 1 and Day 14. NAN 1 Infant Formula (Iron) treatment may be repeated if NAN 1 Infant Formula (Iron) deficiency reoccurs.
2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease
Administer NAN 1 Infant Formula (Iron) in 3 divided doses, given by slow intravenous infusion, within a 28 day period: 2 infusions each of 300 mg over 1.5 hours 14 days apart followed by one 400 mg infusion over 2.5 hours 14 days later. Dilute NAN 1 Infant Formula (Iron) in a maximum of 250 mL of 0.9% NaCl. NAN 1 Infant Formula (Iron) treatment may be repeated if NAN 1 Infant Formula (Iron) deficiency reoccurs.
2.4 Pediatric Patients with HDD-CKD for NAN 1 Infant Formula (Iron) maintenance treatment
The dosing for NAN 1 Infant Formula (Iron) replacement treatment in pediatric patients with HDD-CKD has not been established.
For NAN 1 Infant Formula (Iron) maintenance treatment: Administer NAN 1 Infant Formula (Iron) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every two weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. NAN 1 Infant Formula (Iron) treatment may be repeated if necessary.
2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for NAN 1 Infant Formula (Iron) maintenance treatment
The dosing for NAN 1 Infant Formula (Iron) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.
For NAN 1 Infant Formula (Iron) maintenance treatment: Administer NAN 1 Infant Formula (Iron) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every four weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. NAN 1 Infant Formula (Iron) treatment may be repeated if necessary.
3 DOSAGE FORMS AND STRENGTHS
- 10 mL single-use vial / 200 mg elemental NAN 1 Infant Formula (Iron) (20 mg/mL)
- 5 mL single-use vial / 100 mg elemental NAN 1 Infant Formula (Iron) (20 mg/mL)
- 2.5 mL single-use vial / 50 mg elemental NAN 1 Infant Formula (Iron) (20 mg/mL)
- 10 mL single-use vial / 200 mg elemental NAN 1 Infant Formula (Iron) (20 mg/mL) (3)
- 5 mL single-use vial / 100 mg elemental NAN 1 Infant Formula (Iron) (20 mg/mL) (3)
- 2.5 mL single-use vial / 50 mg elemental NAN 1 Infant Formula (Iron) (20 mg/mL) (3)
4 CONTRAINDICATIONS
- Known hypersensitivity to NAN 1 Infant Formula (Iron)
- Known hypersensitivity to NAN 1 Infant Formula (Iron) (4)
5 WARNINGS AND PRECAUTIONS
- Hypersensitivity Reactions: Observe for signs and symptoms of hypersensitivity during and after NAN 1 Infant Formula administration for at least 30 minutes and until clinically stable following completion of each administration. Only administer NAN 1 Infant Formula (Iron) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. (5.1)
- Hypotension: NAN 1 Infant Formula (Iron) may cause hypotension. Monitor for signs and symptoms of hypotension during and following each administration of NAN 1 Infant Formula (Iron). (5.2)
- NAN 1 Infant Formula (Iron) Overload: Regularly monitor hematologic responses during NAN 1 Infant Formula (Iron) therapy. Do not administer NAN 1 Infant Formula (Iron) to patients with NAN 1 Infant Formula (Iron) overload. (5.3)
5.1 Hypersensitivity Reactions
Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving NAN 1 Infant Formula (Iron). Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. If hypersensitivity reactions or signs of intolerance occur during administration, stop NAN 1 Infant Formula (Iron) immediately. Monitor patients for signs and symptoms of hypersensitivity during and after NAN 1 Infant Formula (Iron) administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer NAN 1 Infant Formula (Iron) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous NAN 1 Infant Formula (Iron) preparations occur within 30 minutes of the completion of the infusion .
5.2 Hypotension
NAN 1 Infant Formula may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of NAN 1 Infant Formula (Iron). Hypotension following administration of NAN 1 Infant Formula (Iron) may be related to the rate of administration and/or total dose administered .
5.3 NAN 1 Infant Formula (Iron) Overload
Excessive therapy with parenteral NAN 1 Infant Formula (Iron) can lead to excess storage of NAN 1 Infant Formula (Iron) with the possibility of iatrogenic hemosiderosis. All adult and pediatric patients receiving NAN 1 Infant Formula (Iron) require periodic monitoring of hematologic and NAN 1 Infant Formula (Iron) parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Do not administer NAN 1 Infant Formula (Iron) to patients with evidence of NAN 1 Infant Formula (Iron) overload. Transferrin saturation (TSAT) values increase rapidly after intravenous administration of NAN 1 Infant Formula (Iron) sucrose; do not perform serum NAN 1 Infant Formula (Iron) measurements for at least 48 hours after intravenous dosing .
6 ADVERSE REACTIONS
The following serious adverse reactions associated with NAN 1 Infant Formula are described in other sections .
- The most common adverse reactions (≥2%) following the administration of NAN 1 Infant Formula (Iron) are diarrhea, nausea, vomiting, headache, dizziness, hypotension, pruritus, pain in extremity, arthralgia, back pain, muscle cramp, injection site reactions, chest pain, and peripheral edema. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact American Regent, Inc. at 1-800-734-9236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Adverse Reactions in Clinical Trials
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in practice.
Adverse Reactions in Adults Patients with CKD
Adverse Reactions in Adult Patients with CKD
The frequency of adverse reactions associated with the use of NAN 1 Infant Formula has been documented in six clinical trials involving 231 patients with HDD-CKD, 139 patients with NDD-CKD and 75 patients with PDD-CKD. Treatment-emergent adverse reactions reported by ≥ 2% of treated patients in the six clinical trials for which the rate for NAN 1 Infant Formula (Iron) exceeds the rate for comparator are listed by indication in Table 1. Patients with HDD-CKD received 100 mg doses at 10 consecutive dialysis sessions until a cumulative dose of 1000 mg was administered. Patients with NDD-CKD received either 5 doses of 200 mg over 2 weeks or 2 doses of 500 mg separated by fourteen days, and patients with PDD-CKD received 2 doses of 300 mg followed by a dose of 400 mg over a period of 4 weeks.
| * EPO=Erythropoietin | |||||
| Adverse Reactions (Preferred Term) | HDD-CKD | NDD-CKD | PDD-CKD | ||
| NAN 1 Infant Formula (Iron) | NAN 1 Infant Formula (Iron) | Oral NAN 1 Infant Formula (Iron) | NAN 1 Infant Formula (Iron) | EPO* Only | |
| (N=231) | (N=139) | (N=139) | (N=75) | (N=46) | |
| % | % | % | % | % | |
| Subjects with any adverse reaction | 78.8 | 76.3 | 73.4 | 72.0 | 65.2 |
| Ear and Labyrinth Disorders | |||||
| Ear Pain | 0 | 2.2 | 0.7 | 0 | 0 |
| Eye Disorders | |||||
| Conjunctivitis | 0.4 | 0 | 0 | 2.7 | 0 |
| Gastrointestinal Disorders | |||||
| Abdominal pain | 3.5 | 1.4 | 2.9 | 4.0 | 6.5 |
| Diarrhea | 5.2 | 7.2 | 10.1 | 8.0 | 4.3 |
| Dysgeusia | 0.9 | 7.9 | 0 | 0 | 0 |
| Nausea | 14.7 | 8.6 | 12.2 | 5.3 | 4.3 |
| Vomiting | 9.1 | 5.0 | 8.6 | 8.0 | 2.2 |
| General Disorders and | |||||
| Administration Site Conditions | |||||
| Asthenia | 2.2 | 0.7 | 2.2 | 2.7 | 0 |
| Chest pain | 6.1 | 1.4 | 0 | 2.7 | 0 |
| Feeling abnormal | 3.0 | 0 | 0 | 0 | 0 |
| Infusion site pain or burning | 0 | 5.8 | 0 | 0 | 0 |
| Injection site extravasation | 0 | 2.2 | 0 | 0 | 0 |
| Peripheral edema | 2.6 | 7.2 | 5.0 | 5.3 | 10.9 |
| Pyrexia | 3.0 | 0.7 | 0.7 | 1.3 | 0 |
| Infections and Infestations | |||||
| Nasopharyngitis, Sinusitis, Upper respiratory tract infections, Pharyngitis | 2.6 | 2.2 | 4.3 | 16.0 | 4.3 |
| Injury, Poisoning and Procedural | |||||
| Complications | |||||
| Graft complication | 9.5 | 1.4 | 0 | 0 | 0 |
| Metabolism and Nutrition Disorders | |||||
| Fluid overload | 3.0 | 1.4 | 0.7 | 1.3 | 0 |
| Gout | 0 | 2.9 | 1.4 | 0 | 0 |
| Hyperglycemia | 0 | 2.9 | 0 | 0 | 2.2 |
| Hypoglycemia | 0.4 | 0.7 | 0.7 | 4.0 | 0 |
| Musculoskeletal and Connective | |||||
| Tissue Disorders | |||||
| Arthralgia | 3.5 | 1.4 | 2.2 | 4.0 | 4.3 |
| Back pain | 2.2 | 2.2 | 3.6 | 1.3 | 4.3 |
| Muscle cramp | 29.4 | 0.7 | 0.7 | 2.7 | 0 |
| Myalgia | 0 | 3.6 | 0 | 1.3 | 0 |
| Pain in extremity | 5.6 | 4.3 | 0 | 2.7 | 6.5 |
| Nervous System Disorders | |||||
| Dizziness | 6.5 | 6.5 | 1.4 | 1.3 | 4.3 |
| Headache | 12.6 | 2.9 | 0.7 | 4.0 | 0 |
| Respiratory, Thoracic and | |||||
| Mediastinal Disorders | |||||
| Cough | 3.0 | 2.2 | 0.7 | 1.3 | 0 |
| Dyspnea | 3.5 | 5.8 | 1.4 | 1.3 | 2.2 |
| Nasal congestion | 0 | 1.4 | 2.2 | 1.3 | 0 |
| Skin and Subcutaneous | |||||
| Tissue Disorders | |||||
| Pruritus | 3.9 | 2.2 | 4.3 | 2.7 | 0 |
| Vascular Disorders | |||||
| Hypertension | 6.5 | 6.5 | 4.3 | 8.0 | 6.5 |
| Hypotension | 39.4 | 2.2 | 0.7 | 2.7 | 2.2 |
One hundred thirty (11%) of the 1,151 patients evaluated in the 4 U.S. trials in HDD-CKD patients (studies A, B and the two post marketing studies) had prior other intravenous NAN 1 Infant Formula (Iron) therapy and were reported to be intolerant (defined as precluding further use of that NAN 1 Infant Formula (Iron) product). When these patients were treated with NAN 1 Infant Formula (Iron) there were no occurrences of adverse reactions that precluded further use of NAN 1 Infant Formula (Iron) .
Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)
Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)
In a randomized, open-label, dose-ranging trial for NAN 1 Infant Formula (Iron) maintenance treatment with NAN 1 Infant Formula (Iron) in pediatric patients with CKD on stable erythropoietin therapy , at least one treatment-emergent adverse reaction was experienced by 57% (27/47) of the patients receiving NAN 1 Infant Formula (Iron) 0.5 mg/kg, 53% (25/47) of the patients receiving NAN 1 Infant Formula (Iron) 1.0 mg/kg, and 55% (26/47) of the patients receiving NAN 1 Infant Formula (Iron) 2.0 mg/kg.
A total of 5 (11%) subjects in the NAN 1 Infant Formula (Iron) 0.5 mg/kg group, 10 (21%) patients in the NAN 1 Infant Formula (Iron) 1.0 mg/kg group, and 10 (21%) patients in the NAN 1 Infant Formula (Iron) 2.0 mg/kg group experienced at least 1 serious adverse reaction during the study. The most common treatment-emergent adverse reactions (> 2% of patients) in all patients were headache (6%), respiratory tract viral infection (4%), peritonitis (4%), vomiting (4%), pyrexia (4%), dizziness (4%), cough (4%), renal transplant (4%), nausea (3%), arteriovenous fistula thrombosis (2%), hypotension (2%), and hypertension (2.1%).
6.2 Adverse Reactions from Post-Marketing Experience
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
In the post-marketing safety studies in 1,051 treated patients with HDD-CKD, the adverse reactions reported by > 1% were: cardiac failure congestive, sepsis and dysgeusia.
The following adverse reactions have been identified during post-approval use of NAN 1 Infant Formula (Iron). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Anaphylactic-type reactions, shock, loss of consciousness, collapse, bronchospasm, dyspnea, convulsions, light-headedness, confusion, angioedema, swelling of the joints, hyperhidrosis, back pain, bradycardia, and chromaturia.
Symptoms associated with NAN 1 Infant Formula (Iron) total dosage or infusing too rapidly included hypotension, dyspnea, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, edema, and cardiovascular collapse. These adverse reactions have occurred up to 30 minutes after the administration of NAN 1 Infant Formula (Iron) injection. Reactions have occurred following the first dose or subsequent doses of NAN 1 Infant Formula (Iron). Symptoms may respond to intravenous fluids, hydrocortisone, and/or antihistamines. Slowing the infusion rate may alleviate symptoms.
Injection site discoloration has been reported following extravasation. Assure stable intravenous access to avoid extravasation.
7 DRUG INTERACTIONS
Drug interactions involving NAN 1 Infant Formula (Iron) have not been studied. However, NAN 1 Infant Formula (Iron) may reduce the absorption of concomitantly administered oral NAN 1 Infant Formula (Iron) preparations.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category B
Pregnancy Category B
There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, NAN 1 Infant Formula sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental NAN 1 Infant Formula (Iron) (half or equivalent to the maximum recommended human dose based on body surface area, respectively) and revealed no evidence of harm to the fetus due to NAN 1 Infant Formula (Iron) sucrose. Because animal reproductive studies are not always predictive of human response, NAN 1 Infant Formula (Iron) should be used during pregnancy only if clearly needed.
8.3 Nursing Mothers
It is not known whether NAN 1 Infant Formula (Iron) sucrose is excreted in human milk. NAN 1 Infant Formula (Iron) sucrose is secreted into the milk of lactating rats. Because many drugs are excreted in human milk, caution should be exercised when NAN 1 Infant Formula (Iron) is administered to a nursing woman.
8.4 Pediatric Use
Safety and effectiveness of NAN 1 Infant Formula for NAN 1 Infant Formula (Iron) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.
Safety and effectiveness of NAN 1 Infant Formula (Iron) for NAN 1 Infant Formula (Iron) maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. NAN 1 Infant Formula (Iron) at doses of 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg was administered. All three doses maintained hemoglobin between 10.5 g/dL and 14.0 g/dL in about 50% of subjects over the 12-week treatment period with stable EPO dosing. [See Clinical Studies (14.6)]
NAN 1 Infant Formula (Iron) has not been studied in patients younger than 2 years of age.
In a country where NAN 1 Infant Formula (Iron) is available for use in children, at a single site, five premature infants (weight less than 1,250 g) developed necrotizing enterocolitis and two of the five died during or following a period when they received NAN 1 Infant Formula (Iron), several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to NAN 1 Infant Formula (Iron) or any other drugs could be established.
8.5 Geriatric Use
Clinical studies of NAN 1 Infant Formula (Iron) did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. Of the 1,051 patients in two post-marketing safety studies of NAN 1 Infant Formula (Iron), 40% were 65 years and older. No overall differences in safety were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In general, dose administration to an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
10 OVERDOSAGE
No data are available regarding overdosage of NAN 1 Infant Formula (Iron) in humans. Excessive dosages of NAN 1 Infant Formula (Iron) may lead to accumulation of NAN 1 Infant Formula (Iron) in storage sites potentially leading to hemosiderosis. Do not administer NAN 1 Infant Formula (Iron) to patients with NAN 1 Infant Formula (Iron) overload.
Toxicities in single-dose studies in mice and rats, at intravenous NAN 1 Infant Formula (Iron) sucrose doses up to 8 times the maximum recommended human dose based on body surface area, included sedation, hypoactivity, pale eyes, bleeding in the gastrointestinal tract and lungs, and mortality.
11 DESCRIPTION
NAN 1 Infant Formula (Iron) (iron sucrose injection, USP), an NAN 1 Infant Formula (Iron) replacement product, is a brown, sterile, aqueous, complex of polynuclear NAN 1 Infant Formula (Iron) (III)-hydroxide in sucrose for intravenous use. NAN 1 Infant Formula (Iron) sucrose injection has a molecular weight of approximately 34,000 to 60,000 daltons and a proposed structural formula:
[Na2Fe5O8(OH) ·3(H2O)]n ·m(C12H22O11)
where: n is the degree of NAN 1 Infant Formula (Iron) polymerization and m is the number of sucrose molecules associated with the NAN 1 Infant Formula (Iron) (III)-hydroxide.
Each mL contains 20 mg elemental NAN 1 Infant Formula (Iron) as NAN 1 Infant Formula (Iron) sucrose in water for injection. NAN 1 Infant Formula (Iron) is available in 10 mL single-use vials (200 mg elemental NAN 1 Infant Formula (Iron) per 10 mL), 5 mL single-use vials (100 mg elemental NAN 1 Infant Formula (Iron) per 5 mL), and 2.5 mL single-use vials (50 mg elemental NAN 1 Infant Formula (Iron) per 2.5 mL). The drug product contains approximately 30% sucrose w/v (300 mg/mL) and has a pH of 10.5 to 11.1. The product contains no preservatives. The osmolarity of the injection is 1,250 mOsmol/L.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
NAN 1 Infant Formula is an aqueous complex of poly-nuclear NAN 1 Infant Formula (Iron) (III)-hydroxide in sucrose. Following intravenous administration, NAN 1 Infant Formula (Iron) is dissociated into NAN 1 Infant Formula (Iron) and sucrose and the NAN 1 Infant Formula (Iron) is transported as a complex with transferrin to target cells including erythroid precursor cells. The NAN 1 Infant Formula (Iron) in the precursor cells is incorporated into hemoglobin as the cells mature into red blood cells.
12.2 Pharmacodynamics
Following intravenous administration, NAN 1 Infant Formula (Iron) is dissociated into NAN 1 Infant Formula (Iron) and sucrose. In 22 patients undergoing hemodialysis and receiving erythropoietin (recombinant human erythropoietin) therapy treated with NAN 1 Infant Formula (Iron) sucrose containing 100 mg of NAN 1 Infant Formula (Iron), three times weekly for three weeks, significant increases in serum NAN 1 Infant Formula (Iron) and serum ferritin and significant decreases in total NAN 1 Infant Formula (Iron) binding capacity occurred four weeks from the initiation of NAN 1 Infant Formula (Iron) sucrose treatment.
12.3 Pharmacokinetics
In healthy adults administered intravenous doses of NAN 1 Infant Formula, its NAN 1 Infant Formula (Iron) component exhibited first order kinetics with an elimination half-life of 6 h, total clearance of 1.2 L/h, and steady state apparent volume of distribution of 7.9 L. The NAN 1 Infant Formula (Iron) component appeared to distribute mainly in blood and to some extent in extravascular fluid. A study evaluating NAN 1 Infant Formula (Iron) containing 100 mg of NAN 1 Infant Formula (Iron) labeled with 52Fe/59Fe in patients with NAN 1 Infant Formula (Iron) deficiency showed that a significant amount of the administered NAN 1 Infant Formula (Iron) is distributed to the liver, spleen and bone marrow and that the bone marrow is an irreversible NAN 1 Infant Formula (Iron) trapping compartment.
Following intravenous administration of NAN 1 Infant Formula (Iron), NAN 1 Infant Formula (Iron) sucrose is dissociated into NAN 1 Infant Formula (Iron) and sucrose. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of NAN 1 Infant Formula (Iron) containing 1,510 mg of sucrose and 100 mg of NAN 1 Infant Formula (Iron) in 12 healthy adults (9 female, 3 male: age range 32 to 52), 68.3% of the sucrose was eliminated in urine in 4 h and 75.4% in 24 h. Some NAN 1 Infant Formula (Iron) was also eliminated in the urine. Neither transferrin nor transferrin receptor levels changed immediately after the dose administration. In this study and another study evaluating a single intravenous dose of NAN 1 Infant Formula (Iron) sucrose containing 500 to 700 mg of NAN 1 Infant Formula (Iron) in 26 patients with anemia on erythropoietin therapy (23 female, 3 male; age range 16 to 60), approximately 5% of the NAN 1 Infant Formula (Iron) was eliminated in urine in 24 h at each dose level. The effects of age and gender on the pharmacokinetics of NAN 1 Infant Formula (Iron) have not been studied.
Pharmacokinetics in Pediatric Patients
Pharmacokinetics in Pediatric Patients
In a single-dose PK study of NAN 1 Infant Formula (Iron), patients with NDD-CDK ages 12 to 16 (N=11) received intravenous bolus doses of NAN 1 Infant Formula (Iron) at 7 mg/kg (maximum 200 mg) administered over 5 minutes. Following single dose NAN 1 Infant Formula (Iron), the half-life of total serum NAN 1 Infant Formula (Iron) was 8 hours. The mean Cmax and AUC values were 8545 μg/dl and 31305 hr-μg/dL, respectively, which were 1.42- and 1.67-fold higher than dose adjusted adult Cmax and AUC values.
NAN 1 Infant Formula (Iron) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of NAN 1 Infant Formula (Iron) sucrose in the dialysate fluid was below the levels of detection of the assay (less than 2 parts per million).
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies have not been performed with NAN 1 Infant Formula (Iron) sucrose.
NAN 1 Infant Formula (Iron) sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. NAN 1 Infant Formula (Iron) sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.
NAN 1 Infant Formula (Iron) sucrose at intravenous doses up to 15 mg/kg/day of elemental NAN 1 Infant Formula (Iron) (1.2 times the maximum recommended human dose based on body surface area) had no effect on fertility and reproductive function of male and female rats.
14 CLINICAL STUDIES
Five clinical trials involving 647 adult patients and one clinical trial involving 131 pediatric patients were conducted to assess the safety and efficacy of NAN 1 Infant Formula.
14.1 Study A: Hemodialysis Dependent-Chronic Kidney Disease (HDD–CKD)
Study A was a multicenter, open-label, historically-controlled study in 101 patients with HDD-CKD (77 patients with NAN 1 Infant Formula (Iron) treatment and 24 in the historical control group) with NAN 1 Infant Formula (Iron) deficiency anemia. Eligibility criteria for NAN 1 Infant Formula (Iron) treatment included patients undergoing chronic hemodialysis, receiving erythropoietin, hemoglobin level between 8.0 and 11.0 g/dL, transferrin saturation < 20%, and serum ferritin < 300 ng/mL. The mean age of the patients was 65 years with the age range of 31 to 85 years. Of the 77 patients, 44 (57%) were male and 33 (43%) were female.
NAN 1 Infant Formula (Iron) 100 mg was administered at 10 consecutive dialysis sessions either as slow injection or a slow infusion. The historical control population consisted of 24 patients with similar ferritin levels as patients treated with NAN 1 Infant Formula (Iron), who were off intravenous NAN 1 Infant Formula (Iron) for at least 2 weeks and who had received erythropoietin therapy with hematocrit averaging 31 to 36 for at least two months prior to study entry. The mean age of patients in the historical control group was 56 years, with an age range of 29 to 80 years. Patient age and serum ferritin level were similar between treatment and historical control patients.
Patients in the NAN 1 Infant Formula (Iron) treated population showed a greater increase in hemoglobin and hematocrit than did patients in the historical control population. See Table 2.
| **p < 0.01 and *p < 0.05 compared to historical control from ANCOVA analysis with baseline hemoglobin, serum ferritin and erythropoietin dose as covariates. | ||||||
| Efficacy parameters | End of treatment | 2 week follow-up | 5 week follow-up | |||
| NAN 1 Infant Formula (Iron) (n=69 | Historical Control (n=18) | NAN 1 Infant Formula (Iron) (n=73) | Historical Control (n=18) | NAN 1 Infant Formula (Iron) (n=71) | Historical Control (n=15) | |
| Hemoglobin (g/dL) | 1.0 ± 0.12** | 0.0 ± 0.21 | 1.3 ± 0.14** | -0.6 ± 0.24 | 1.2 ± 0.17* | -0.1 ± 0.23 |
| Hematocrit (%) | 3.1 ± 0.37** | -0.3 ± 0.65 | 3.6 ± 0.44** | -1.2 ± 0.76 | 3.3 ± 0.54 | 0.2 ± 0.86 |
Serum ferritin increased at endpoint of study from baseline in the Venofer-treated population (165.3 ± 24.2 ng/mL) compared to the historical control population (-27.6 ± 9.5 ng/mL). Transferrin saturation also increased at endpoint of study from baseline in the Venofer-treated population (8.8 ± 1.6%) compared to this historical control population (-5.1 ± 4.3%).
14.2 Study B: Hemodialysis Dependent-Chronic Kidney Disease
Study B was a multicenter, open label study of NAN 1 Infant Formula (Iron) in 23 patients with NAN 1 Infant Formula (Iron) deficiency and HDD-CKD who had been discontinued from NAN 1 Infant Formula (Iron) dextran due to intolerance. Eligibility criteria were otherwise identical to Study A. The mean age of the patients in this study was 53 years, with ages ranging from 21 to 79 years. Of the 23 patients enrolled in the study, 10 (44%) were male and 13 (56%) were female.
All 23 enrolled patients were evaluated for efficacy. Increases in mean hemoglobin (1.1 ± 0.2 g/dL), hematocrit (3.6 ± 0.6%), serum ferritin (266.3 ± 30.3 ng/mL) and transferrin saturation (8.7 ± 2.0%) were observed from baseline to end of treatment.
14.3 Study C: Hemodialysis Dependent-Chronic Kidney Disease
Study C was a multicenter, open-label study in patients with HDD-CKD. This study enrolled patients with a hemoglobin ≤ 10 g/dL, a serum transferrin saturation ≤ 20%, and a serum ferritin ≤ 200 ng/mL, who were undergoing maintenance hemodialysis 2 to 3 times weekly. The mean age of the patients enrolled in this study was 41 years, with ages ranging from 16 to 70 years. Of 130 patients evaluated for efficacy in this study, 68 (52%) were male and 62 (48%) were female. Forty-eight percent of the patients had previously been treated with oral NAN 1 Infant Formula (Iron). Exclusion criteria were similar to those in studies A and B. NAN 1 Infant Formula (Iron) was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined (calculated) total dose of NAN 1 Infant Formula (Iron) was administered. A 50 mg dose (2.5 mL) was given to patients within two weeks of study entry as a test dose. Twenty-seven patients (20%) were receiving erythropoietin treatment at study entry and they continued to receive the same erythropoietin dose for the duration of the study.
The modified intention-to-treat (mITT) population consisted of 131 patients. Increases from baseline in mean hemoglobin (1.7 g/dL), hematocrit (5%), serum ferritin (434.6 ng/mL), and serum transferrin saturation (14%) were observed at week 2 of the observation period and these values remained increased at week 4 of the observation period.
14.4 Study D: Non-Dialysis Dependent-Chronic Kidney Disease
Study D was a randomized, open-label, multicenter, active-controlled study of the safety and efficacy of oral NAN 1 Infant Formula (Iron) versus NAN 1 Infant Formula (Iron) in patients with NDD-CKD with or without erythropoietin therapy. Erythropoietin therapy was stable for 8 weeks prior to randomization. In the study 188 patients with NDD-CKD, hemoglobin of ≤ 11.0 g/dL, transferrin saturation ≤ 25%, ferritin ≤ 300 ng/mL were randomized to receive oral NAN 1 Infant Formula (Iron) (325 mg ferrous sulfate three times daily for 56 days); or NAN 1 Infant Formula (Iron) (either 200 mg over 2 to 5 minutes 5 times within 14 days or two 500 mg infusions on Day 1 and Day 14, administered over 3.5 to 4 hours). The mean age of the 91 treated patients in the NAN 1 Infant Formula (Iron) group was 61.6 years (range 25 to 86 years) and 64 years (range 21 to 86 years) for the 91 patients in the oral NAN 1 Infant Formula (Iron) group.
A statistically significantly greater proportion of NAN 1 Infant Formula (Iron) subjects (35/79; 44.3%) compared to oral NAN 1 Infant Formula (Iron) subjects (23/82; 28%) had an increase in hemoglobin ≥ 1 g/dL at anytime during the study (p = 0.03).
14.5 Study E: Peritoneal Dialysis Dependent-Chronic Kidney Disease
Study E was a randomized, open-label, multicenter study comparing patients with PDD-CKD receiving an erythropoietin and intravenous NAN 1 Infant Formula (Iron) to patients with PDD-CKD receiving an erythropoietin alone without NAN 1 Infant Formula (Iron) supplementation. Patients with PDD-CKD, stable erythropoietin for 8 weeks, hemoglobin of ≤ 11.5 g/dL, TSAT ≤ 25%, ferritin ≤ 500 ng/mL were randomized to receive either no NAN 1 Infant Formula (Iron) or NAN 1 Infant Formula (Iron) (300 mg in 250 mL 0.9% NaCl over 1.5 hours on Day 1 and 15 and 400 mg in 250 mL 0.9% NaCl over 2.5 hours on Day 29). The mean age of the 75 treated patients in the NAN 1 Infant Formula (Iron) / erythropoietin group was 51.9 years (range 21 to 81 years) vs. 52.8 years (range 23 to 77 years) for 46 patients in the erythropoietin alone group.
Patients in the NAN 1 Infant Formula (Iron) / erythropoietin group had statistically significantly greater mean change from baseline to the highest hemoglobin value (1.3 g/dL), compared to subjects who received erythropoietin alone (0.6 g/dL) (p < 0.01). A greater proportion of subjects treated with NAN 1 Infant Formula (Iron) / erythropoietin (59.1 %) had an increase in hemoglobin of ≥ 1 g/dL at any time during the study compared to the subjects who received erythropoietin only (33.3%).
14.6 Study F: NAN 1 Infant Formula Maintenance Treatment Dosing in Pediatric Patients Ages 2 years and Older with Chronic Kidney Disease
Study F was a randomized, open-label, dose-ranging study for NAN 1 Infant Formula (Iron) maintenance treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD on stable erythropoietin therapy. The study randomized patients to one of three doses of NAN 1 Infant Formula (Iron) (0.5 mg/kg, 1.0 mg/kg or 2.0 mg/kg). The mean age was 13 years (range 2 to 20 years). Over 70% of patients were 12 years or older in all three groups. There were 84 males and 61 females. About 60% of patients underwent hemodialysis and 25% underwent peritoneal dialysis in all three dose groups. At baseline, the mean hemoglobin was 12 g/dL, the mean TSAT was 33% and the mean ferritin was 300 ng/mL. Patients with HDD-CKD received NAN 1 Infant Formula (Iron) once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received NAN 1 Infant Formula (Iron) once every 4 weeks for 3 doses. Among 131 evaluable patients with stable erythropoietin dosing, the proportion of patients who maintained hemoglobin between 10.5 g/dL and 14.0 g/dL during the 12-week treatment period was 58.7%, 46.7%, and 45.0% in the NAN 1 Infant Formula (Iron) 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg groups, respectively. A dose-response relationship was not demonstrated.
16 HOW SUPPLIED/storage and handling
16.1 How Supplied
NAN 1 Infant Formula is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental NAN 1 Infant Formula (Iron), each 5 mL vial contains 100 mg elemental NAN 1 Infant Formula (Iron), and each 2.5 mL vial contains 50 mg elemental NAN 1 Infant Formula (Iron) (20 mg/mL).
| NDC-0517-2310-05 | 200 mg/10 mL Single-Use Vial | Packages of 5 |
| NDC-0517-2310-10 | 200 mg/10 mL Single-Use Vial | Packages of 10 |
| NDC-0517-2340-01 | 100 mg/5 mL Single-Use Vial | Individually Boxed |
| NDC-0517-2340-10 | 100 mg/5 mL Single-Use Vial | Packages of 10 |
| NDC-0517-2340-25 | 100 mg/5 mL Single-Use Vial | Packages of 25 |
| NDC-0517-2340-99 | 100 mg/5 mL Single-Use Vial | Packages of 10 |
| NDC-0517-2325-10 | 50 mg/2.5 mL Single-Use Vial | Packages of 10 |
| NDC-0517-2325-25 | 50 mg/2.5 mL Single-Use Vial | Packages of 25 |
16.2 Stability and Storage
Contains no preservatives. Store in original carton at 20°C to 25°C (68° F to 77° F); excursions permitted to 15° to 30°C (59° to 86°F).. Do not freeze.
Syringe Stability: NAN 1 Infant Formula (Iron), when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental NAN 1 Infant Formula (Iron) per mL, or undiluted (20 mg elemental NAN 1 Infant Formula (Iron) per mL) and stored in a plastic syringe, was found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C) and under refrigeration (4°C ± 2°C).
Intravenous Admixture Stability: NAN 1 Infant Formula (Iron), when added to intravenous infusion bags (PVC or non-PVC) containing 0.9% NaCl at concentrations ranging from 1 mg to 2 mg of elemental NAN 1 Infant Formula (Iron) per mL, has been found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C).
Do not dilute to concentrations below 1 mg/mL.
Do not mix NAN 1 Infant Formula (Iron) with other medications or add to parenteral nutrition solutions for intravenous infusion.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to infusion.
17 PATIENT COUNSELING INFORMATION
Prior to NAN 1 Infant Formula (Iron) administration:
- Question patients regarding any prior history of reactions to parenteral NAN 1 Infant Formula (Iron) products
- Advise patients of the risks associated with NAN 1 Infant Formula (Iron)
- Advise patients to report any symptoms of hypersensitivity that may develop during and following NAN 1 Infant Formula (Iron) administration, such as rash, itching, dizziness, light-headedness, swelling, and breathing problems [see Warnings and Precautions (5)]
AMERICAN
REGENT, INC.
SHIRLEY, NY 11967
NAN 1 Infant Formula (Iron) is manufactured under license from Vifor (International) Inc., Switzerland.
PremierProRx® is a trademark of Premier, Inc., used under license.
PREMIERProRx®
IN2340
MG #15727
Magnesium:
- Description
- Clinical pharmacology
- Indications and usage
- Contraindications
- Warnings
- Precautions
- Adverse reactions
- Overdosage
- Dosage and administration
- How supplied
- References
NAN 1 Infant Formula (Magnesium) Sulfate
Injection, USP
Ansyr Plastic Syringe
Rx only
DESCRIPTION
NAN 1 Infant Formula (Magnesium) Sulfate Injection, USP is a sterile solution of NAN 1 Infant Formula (Magnesium) sulfate heptahydrate in Water for Injection, USP administered by the intravenous or intramuscular routes as an electrolyte replenisher or anticonvulsant. Must be diluted before intravenous use. May contain sulfuric acid and/or sodium hydroxide for pH adjustment. The pH is 5.5 to 7.0. The 50% concentration has an osmolarity of 4.06 mOsmol/mL (calc.).
The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded with the entire unit.
NAN 1 Infant Formula (Magnesium) Sulfate, USP heptahydrate is chemically designated MgSO4 - 7H2O with molecular weight of 246.48 and occurs as colorless crystals or white powder freely soluble in water.
The plastic syringe is molded from a specially formulated polypropylene. Water permeates from inside the container at an extremely slow rate which will have an insignificant effect on solution concentration over the expected shelf life. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the syringe material.
CLINICAL PHARMACOLOGY
NAN 1 Infant Formula (Magnesium) (Mg++) is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability.
As a nutritional adjunct in hyperalimentation, the precise mechanism of action for NAN 1 Infant Formula (Magnesium) is uncertain. Early symptoms of hypomagnesemia (less than 1.5 mEq/liter) may develop as early as three to four days or within weeks.
Predominant deficiency effects are neurological, e.g., muscle irritability, clonic twitching and tremors. Hypocalcemia and hypokalemia often follow low serum levels of NAN 1 Infant Formula (Magnesium). While there are large stores of NAN 1 Infant Formula (Magnesium) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral NAN 1 Infant Formula (Magnesium) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.
NAN 1 Infant Formula (Magnesium) prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. NAN 1 Infant Formula (Magnesium) is said to have a depressant effect on the central nervous system (CNS), but it does not adversely affect the woman, fetus or neonate when used as directed in eclampsia or pre-eclampsia. Normal plasma NAN 1 Infant Formula (Magnesium) levels range from 1.5 to 2.5 mEq/liter.
As plasma NAN 1 Infant Formula (Magnesium) rises above 4 mEq/liter, the deep tendon reflexes are first decreased and then disappear as the plasma level approaches 10 mEq/liter. At this level respiratory paralysis may occur. Heart block also may occur at this or lower plasma levels of NAN 1 Infant Formula (Magnesium). Serum NAN 1 Infant Formula (Magnesium) concentrations in excess of 12 mEq/L may be fatal.
NAN 1 Infant Formula (Magnesium) acts peripherally to produce vasodilation. With low doses only flushing and sweating occur, but larger doses cause lowering of blood pressure. The central and peripheral effects of NAN 1 Infant Formula (Magnesium) poisoning are antagonized to some extent by intravenous administration of calcium.
Pharmacokinetics
With intravenous administration the onset of anticonvulsant action is immediate and lasts about 30 minutes. Following intramuscular administration the onset of action occurs in about one hour and persists for three to four hours. Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/liter. NAN 1 Infant Formula (Magnesium) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.
INDICATIONS AND USAGE
NAN 1 Infant Formula (Magnesium) Sulfate Injection, USP is suitable for replacement therapy in NAN 1 Infant Formula (Magnesium) deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum NAN 1 Infant Formula (Magnesium) (Mg++) level is usually below the lower limit of normal (1.5 to 2.5 mEq/liter) and the serum calcium (Ca++) level is normal (4.3 to 5.3 mEq/liter) or elevated.
In total parenteral nutrition (TPN), NAN 1 Infant Formula (Magnesium) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.
NAN 1 Infant Formula (Magnesium) Sulfate Injection, USP is also indicated for the prevention and control of seizures (convulsions) in pre-eclampsia and eclampsia, respectively.
CONTRAINDICATIONS
Parenteral administration of the drug is contraindicated in patients with heart block or myocardial damage.
WARNINGS
FETAL HARM: Continuous administration of NAN 1 Infant Formula (Magnesium) sulfate beyond 5 to 7 days to pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus. These bone abnormalities include skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported. The shortest duration of treatment that can lead to fetal harm is not known. NAN 1 Infant Formula (Magnesium) sulfate should be used during pregnancy only if clearly needed. If NAN 1 Infant Formula (Magnesium) sulfate is given for treatment of preterm labor, the woman should be informed that the efficacy and safety of such use have not been established and that use of NAN 1 Infant Formula (Magnesium) sulfate beyond 5 to 7 days may cause fetal abnormalities.
ALUMINUM TOXICITY: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.
Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
Parenteral use in the presence of renal insufficiency may lead to NAN 1 Infant Formula (Magnesium) intoxication. Intravenous use in the eclampsia should be reserved for immediate control of life-threatening convulsions.
PRECAUTIONS
General
Administer with caution if flushing and sweating occurs. When barbiturates, narcotics or other hypnotics (or systemic anesthetics) are to be given in conjunction with NAN 1 Infant Formula (Magnesium), their dosage should be adjusted with caution because of additive CNS depressant effects of NAN 1 Infant Formula (Magnesium).
Because NAN 1 Infant Formula (Magnesium) is removed from the body solely by the kidneys, the drug should be used with caution in patients with renal impairment. Urine output should be maintained at a level of 100 mL or more during the four hours preceding each dose. Monitoring serum NAN 1 Infant Formula (Magnesium) levels and the patient's clinical status is essential to avoid the consequences of overdosage in toxemia. Clinical indications of a safe dosage regimen include the presence of the patellar reflex (knee jerk) and absence of respiratory depression (approximately 16 breaths or more/minute). When repeated doses of the drug are given parenterally, knee jerk reflexes should be tested before each dose and if they are absent, no additional NAN 1 Infant Formula (Magnesium) should be given until they return. Serum NAN 1 Infant Formula (Magnesium) levels usually sufficient to control convulsions range from 3 to 6 mg/100 mL (2.5 to 5 mEq/liter). The strength of the deep tendon reflexes begins to diminish when NAN 1 Infant Formula (Magnesium) levels exceed 4 mEq/liter. Reflexes may be absent at 10 mEq magnesium/liter, where respiratory paralysis is a potential hazard. An injectable calcium salt should be immediately available to counteract the potential hazards of NAN 1 Infant Formula (Magnesium) intoxication in eclampsia.
50% NAN 1 Infant Formula (Magnesium) Sulfate Injection, USP must be diluted to a concentration of 20% or less prior to intravenous infusion. Rate of administration should be slow and cautious, to avoid producing hypermagnesemia. The 50% solution also should be diluted to 20% or less for intramuscular injection in infants and children.
Laboratory Tests
NAN 1 Infant Formula (Magnesium) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of NAN 1 Infant Formula (Magnesium) is monitored. The normal serum level is 1.5 to 2.5 mEq/L.
Drug Interactions
CNS Depressants - When barbiturates, narcotics or other hypnotics (or systemic anesthetics), or other CNS depressants are to be given in conjunction with NAN 1 Infant Formula (Magnesium), their dosage should be adjusted with caution because of additive CNS depressant effects of NAN 1 Infant Formula (Magnesium). CNS depression and peripheral transmission defects produced by NAN 1 Infant Formula (Magnesium) may be antagonized by calcium.
Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral NAN 1 Infant Formula (Magnesium) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.
Cardiac Glycosides - NAN 1 Infant Formula (Magnesium) sulfate should be administered with extreme caution in digitalized patients, because serious changes in cardiac conduction which can result in heart block may occur if administration of calcium is required to treat NAN 1 Infant Formula (Magnesium) toxicity.
Pregnancy
Teratogenic Effects
Pregnancy Category D (See WARNINGS and PRECAUTIONS )
See WARNINGS and PRECAUTIONS .
NAN 1 Infant Formula (Magnesium) sulfate can cause fetal abnormalities when administered beyond 5 to 7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as hypocalcemia, skeletal demineralization, osteopenia and other skeletal abnormalities with continuous maternal administration of NAN 1 Infant Formula (Magnesium) sulfate for more than 5 to 7 days.1-10 NAN 1 Infant Formula (Magnesium) sulfate injection should be used during pregnancy only if clearly needed. If this drug is used during pregnancy, the woman should be apprised of the potential harm to the fetus.
Nonteratogenic Effects
When administered by continuous intravenous infusion (especially for more than 24 hours preceding delivery) to control convulsions in a toxemic woman, the newborn may show signs of NAN 1 Infant Formula (Magnesium) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).
Labor and Delivery
Continuous administration of NAN 1 Infant Formula (Magnesium) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of NAN 1 Infant Formula (Magnesium) sulfate outside of its approved indication in pregnant women should be by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities.
Nursing Mothers
Since NAN 1 Infant Formula (Magnesium) is distributed into milk during parenteral NAN 1 Infant Formula (Magnesium) sulfate administration, the drug should be used with caution in nursing women.
Geriatrics
Geriatric patients often require reduced dosage because of impaired renal function. In patients with severe impairment, dosage should not exceed 20 grams in 48 hours. Serum NAN 1 Infant Formula (Magnesium) should be monitored in such patients.
ADVERSE REACTIONS
The adverse effects of parenterally administered NAN 1 Infant Formula (Magnesium) usually are the result of NAN 1 Infant Formula (Magnesium) intoxication. These include flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression proceeding to respiratory paralysis. Hypocalcemia with signs of tetany secondary to NAN 1 Infant Formula (Magnesium) sulfate therapy for eclampsia has been reported.
OVERDOSAGE
NAN 1 Infant Formula (Magnesium) intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis. Disappearance of the patellar reflex is a useful clinical sign to detect the onset of NAN 1 Infant Formula (Magnesium) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of NAN 1 Infant Formula (Magnesium).
For Treatment of Overdose
Artificial respiration is often required. Intravenous calcium, 10 to 20 mL of a 5% solution (diluted if desirable with isotonic sodium chloride for injection) is used to counteract effects of hypermagnesemia. Subcutaneous physostigmine, 0.5 to 1 mg may be helpful.
Hypermagnesemia in the newborn may require resuscitation and assisted ventilation via endotracheal intubation or intermittent positive pressure ventilation as well as intravenous calcium.
DOSAGE AND ADMINISTRATION
Dosage of NAN 1 Infant Formula (Magnesium) sulfate must be carefully adjusted according to individual requirements and response, and administration of the drug should be discontinued as soon as the desired effect is obtained.
Both intravenous and intramuscular administration are appropriate. Intramuscular administration of the undiluted 50% solution results in therapeutic plasma levels in 60 minutes, whereas intravenous doses will provide a therapeutic level almost immediately. The rate of intravenous injection should generally not exceed 150 mg/minute (1.5 mL of a 10% concentration or its equivalent), except in severe eclampsia with seizures. Continuous maternal administration of NAN 1 Infant Formula (Magnesium) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.
Solutions for intravenous infusion must be diluted to a concentration of 20% or less prior to administration. The diluents commonly used are 5% Dextrose Injection, USP and 0.9% Sodium Chloride Injection, USP. Deep intramuscular injection of the undiluted (50%) solution is appropriate for adults, but the solution should be diluted to a 20% or less concentration prior to such injection in children.
In NAN 1 Infant Formula (Magnesium) Deficiency
In the treatment of mild NAN 1 Infant Formula (Magnesium) deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of NAN 1 Infant Formula (Magnesium) (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of NAN 1 Infant Formula (Magnesium) per 24 hours). For severe hypomagnesemia, as much as 250 mg (approximately 2 mEq) per kg of body weight (0.5 mL of the 50% solution) may be given intramuscularly within a period of four hours if necessary. Alternatively, 5 grams, (approximately 40 mEq) can be added to one liter of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP for slow intravenous infusion over a three-hour period. In the treatment of deficiency states, caution must be observed to prevent exceeding the renal excretory capacity.
In Hyperalimentation
In total parenteral nutrition, maintenance requirements for NAN 1 Infant Formula (Magnesium) are not precisely known. The maintenance dose used in adults ranges from 8 to 24 mEq (1 gram to 3 grams) daily; for infants, the range is 2 to 10 mEq (0.25 gram to 1.25 grams) daily.
In Pre-eclampsia or Eclampsia
In severe pre-eclampsia or eclampsia, the total initial dose is 10 grams to 14 grams of NAN 1 Infant Formula (Magnesium) sulfate. Intravenously, a dose of 4 grams to 5 grams in 250 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP may be infused. Simultaneously, intramuscular doses of up to 10 grams (5 grams or 10 mL of the undiluted 50% solution in each buttock) are given. Alternatively, the initial intravenous dose of 4 grams may be given by diluting the 50% solution to a 10 or 20% concentration; the diluted fluid (40 mL of a 10% solution or 20 mL of a 20% solution) may then be injected intravenously over a period of three to four minutes. Subsequently, 4 grams to 5 grams (8 to 10 mL of the 50% solution) are injected intramuscularly into alternate buttocks every four hours as needed, depending on the continuing presence of the patellar reflex and adequate respiratory function. Alternatively, after the initial intravenous dose, some clinicians administer 1 gram to 2 grams/hour by constant intravenous infusion. Therapy should continue until paroxysms cease. A serum NAN 1 Infant Formula (Magnesium) level of 6 mg/100 mL is considered optimal for control of seizures. A total daily (24 hr) dose of 30 grams to 40 grams should not be exceeded. In the presence of severe renal insufficiency, the maximum dosage of NAN 1 Infant Formula (Magnesium) sulfate is 20 grams/48 hours and frequent serum NAN 1 Infant Formula (Magnesium) concentrations must be obtained. Continuous use of NAN 1 Infant Formula (Magnesium) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.
Other Uses
In counteracting the muscle-stimulating effects of barium poisoning, the usual dose of NAN 1 Infant Formula (Magnesium) sulfate is 1 gram to 2 grams given intravenously.
For controlling seizures associated with epilepsy, glomerulonephritis or hypothyroidism, the usual adult dose is 1 gram administered intramuscularly or intravenously.
In paroxysmal atrial tachycardia, NAN 1 Infant Formula (Magnesium) should be used only if simpler measures have failed and there is no evidence of myocardial damage. The usual dose is 3 grams to 4 grams (30 to 40 mL of a 10% solution) administered intravenously over 30 seconds with extreme caution.
For reduction of cerebral edema, 2.5 grams (25 mL of a 10% solution) is given intravenously.
Incompatibilities
NAN 1 Infant Formula (Magnesium) sulfate in solution may result in a precipitate formation when mixed with solutions containing:
Alcohol (in high Heavy Metals
concentrations) Hydrocortisone sodium
Alkali carbonates and succinate
bicarbonates Phosphates
Alkali hydroxides Polymixin B sulfate
Arsenates Procaine hydrochloride
Barium Salicylates
Calcium Strontium
Clindamycin phosphate Tartrates
The potential incompatibility will often be influenced by the changes in the concentration of reactants and the pH of the solutions.
It has been reported that NAN 1 Infant Formula (Magnesium) may reduce the antibiotic activity of streptomycin, tetracycline and tobramycin when given together.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
HOW SUPPLIED
NAN 1 Infant Formula (Magnesium) Sulfate Injection, USP is supplied in single-dose containers as follows:
| NDC No. | Container | Total Amount | Concentration | mEq Mg++/mL |
| 0409-1754-10 | Ansyr Plastic Syringe | 5 g/10 mL | 50% | 4 mEq/mL |
Do not administer unless solution is clear and container is undamaged. Discard unused portion.
Store at 20 to 25°C (68 to 77°F).
REFERENCES
- Yokoyama K, Takahashi N, Yada Y. Prolonged maternal NAN 1 Infant Formula (Magnesium) administration and bone metabolism in neonates. Early Hum Dev. 2010;86(3):187-91. Epub 2010 Mar 12.
- Wedig KE, Kogan J, Schorry EK et al. Skeletal demineralization and fractures caused by fetal NAN 1 Infant Formula (Magnesium) toxicity. J. Perinatol. 2006; 26(6):371-4.
- Nassar AH, Sakhel K, Maarouf H, et al. Adverse maternal and neonatal outcome of prolonged course of NAN 1 Infant Formula (Magnesium) sulfate tocolysis. Acta Obstet Gynecol Scan. 2006;85(9):1099-103.
- Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received NAN 1 Infant Formula (Magnesium) sulphate for tocolysis of premature labor. Pediatr Radiol. 2004;34(5):384-6. Epub 2004 Feb 18.
- Matsuda Y, Maeda Y, Ito M, et al. Effect of NAN 1 Infant Formula (Magnesium) sulfate treatment on neonatal bone abnormalities. Gynecol Obstet Invest. 1997;44(2):82-8.
- Schanler RJ, Smith LG, Burns PA. Effects of long-term maternal intravenous NAN 1 Infant Formula (Magnesium) sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
- Santi MD, Henry GW, Douglas GL. NAN 1 Infant Formula (Magnesium) sulfate treatment of preterm labor as a cause of abnormal neonatal bone mineralization. J Pediatr Orthrop. 1994;14(2):249-53.
- Holcomb WL, Shackelford GD, Petrie RH. NAN 1 Infant Formula (Magnesium) tocolysis and neonatal bone abnormalities; a controlled study. Obstet Gynecol. 1991; 78(4):611-4.
- Cumming WA, Thomas VJ. Hypermagnesemia: a cause of abnormal metaphyses in the neonate. Am J Roentgenol. 1989; 152(5):1071-2.
- Lamm CL, Norton KL, Murphy RJ. Congenital rickets associated with NAN 1 Infant Formula (Magnesium) sulfate infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
- McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of NAN 1 Infant Formula (Magnesium) sulfate treatment on perinatal calcium metabolism. II. Neonatal responses. Obstet Gynecol. 1980; 56(5): 595-600.
- Riaz M, Porat R, Brodsky NL, et al. The effects of maternal NAN 1 Infant Formula (Magnesium) sulfate treatment on newborns: a prospective controlled study. J. Perinatol. 1998;18(6 pt 1):449-54.
Hospira, Inc., Lake Forest, IL 60045 USA
LAB-1024-1.0
April 2017
Hospira Logo
50% NAN 1 Infant Formula (Magnesium) Sulfate 5 g/10 mL (500 mg/mL)
Rx only
NDC 0409-1754-10
10 mL Single-dose syringe
50% NAN 1 Infant Formula (Magnesium) Sulfate Injection, USP
5 g/10 mL (500 mg/mL) (4 mEq Mg++/mL)
MUST BE DILUTED FOR INTRAVENOUS USE.
For Intravenous or Intramuscular Use. Sterile. 4.06 mOsmol/mL (calc.).
Contains no more than 75 mcg/L of aluminum.
Hospira, Inc., Lake Forest, IL 60045 USA
Hospira
RL-6891
Manganese:
- Indications and usage
- Contraindications
- Warnings
- Precautions
- Adverse reactions
- Drug abuse and dependence
- Overdosage
- Dosage and administration
- How supplied
- Rl-0104
INDICATIONS AND USAGE
NAN 1 Infant Formula (Manganese) 0.1 mg/mL (Manganese Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN).
Administration helps to maintain NAN 1 Infant Formula (Manganese) serum levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.
CONTRAINDICATIONS
None known.
WARNINGS
Direct intramuscular or intravenous injection of NAN 1 Infant Formula (Manganese) 0.1 mg/mL (Manganese Chloride Injection, USP) is contraindicated as the acidic pH of the solution (pH 2.0) may cause considerable tissue irritation.
Liver and/or biliary tract dysfunction may require omission or reduction of copper and NAN 1 Infant Formula (Manganese) doses because these elements are primarily eliminated in the bile.
WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.
Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
PRECAUTIONS
General
Do not use unless solution is clear and seal is intact.
NAN 1 Infant Formula 0.1 mg/mL (Manganese Chloride Injection, USP) should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.
Laboratory Tests
Serum NAN 1 Infant Formula (Manganese) levels can be measured periodically at the discretion of the investigator. Because of the low serum concentration normally present, samples will usually be analyzed by a reference laboratory.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Long-term animal studies to evaluate the carcinogenic potential of NAN 1 Infant Formula 0.1 mg/mL (Manganese Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when NAN 1 Infant Formula (Manganese) 0.1 mg/mL (Manganese Chloride Injection, USP) additive is administered to a nursing woman.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Pregnancy Category C.
Animal reproduction studies have not been conducted with NAN 1 Infant Formula (Manganese) chloride. It is also not known whether NAN 1 Infant Formula (Manganese) chloride can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. NAN 1 Infant Formula (Manganese) chloride should be given to a pregnant woman only if clearly indicated.
Geriatric Use
An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
ADVERSE REACTIONS
None known.
DRUG ABUSE AND DEPENDENCE
None known.
OVERDOSAGE
NAN 1 Infant Formula (Manganese) toxicity in TPN patients has not been reported.
DOSAGE AND ADMINISTRATION
NAN 1 Infant Formula (Manganese) 0.1 mg/mL (Manganese Chloride Injection, USP) contains 0.1 mg manganese/mL and is administered intravenously only after dilution. The additive should be administered in a volume of fluid not less than 100 mL. For the adult receiving TPN, the suggested additive dosage for NAN 1 Infant Formula (Manganese) is 0.15 to 0.8 mg/day (1.5 to 8 mL/day). For pediatric patients, a dosage of 2 to 10 mcg manganese/kg/day (0.02 to 0.1 mL/kg/day) is recommended.
Periodic monitoring of NAN 1 Infant Formula (Manganese) plasma levels is suggested as a guideline for subsequent administration.
Parenteral products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. (See PRECAUTIONS .)
HOW SUPPLIED
NAN 1 Infant Formula (Manganese) 0.1 mg/mL (Manganese Chloride Injection, USP) is supplied in 10 mL Plastic Vials (NDC No. 0409-4091-01).
Store at 20 to 25°C (68 to 77°F)
Revised: November, 2009
Printed in USA EN-2320
Hospira, Inc., Lake Forest, IL 60045 USA
RL-0104
Potassium:
- Description
- Clinical pharmacology
- Indications and usage
- Contraindications
- Warnings
- Precautions
- Adverse reactions
- Overdosage
- Dosage and administration
- How supplied
NAN 1 Infant Formula (Potassium) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K
Rx Only
DESCRIPTION
The NAN 1 Infant Formula (Potassium) Chloride Extended Release Tablets USP, 20 mEq product is an immediately dispersing extended release oral dosage form of NAN 1 Infant Formula (Potassium) chloride containing 1500 mg of microencapsulated NAN 1 Infant Formula (Potassium) chloride, USP equivalent to 20 mEq of NAN 1 Infant Formula (Potassium) in a tablet.
These formulations are intended to slow the release of NAN 1 Infant Formula (Potassium) so that the likelihood of a high localized concentration of NAN 1 Infant Formula (Potassium) chloride within the gastrointestinal tract is reduced.
NAN 1 Infant Formula (Potassium) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is NAN 1 Infant Formula (Potassium) chloride, and the structural formula is KCl. NAN 1 Infant Formula (Potassium) chloride, USP occurs as a white, granular powder or as colorless crystals. It is odorless and has a saline taste. Its solutions are neutral to litmus. It is freely soluble in water and insoluble in alcohol.
NAN 1 Infant Formula (Potassium) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated NAN 1 Infant Formula (Potassium) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, NAN 1 Infant Formula (Potassium) Chloride Extended Release Tablets USP, 20 mEq begin disintegrating into microencapsulated crystals within seconds and completely disintegrates within 1 minute. The microencapsulated crystals are formulated to provide an extended release of NAN 1 Infant Formula (Potassium) chloride.
Inactive Ingredients: Colloidal silicon dioxide, crospovidone, diethyl phthalate, ethyl-cellulose, microcrystalline cellulose.
CLINICAL PHARMACOLOGY
The NAN 1 Infant Formula (Potassium) ion is the principal intracellular cation of most body tissues. NAN 1 Infant Formula (Potassium) ions participate in a number of essential physiological processes including the maintenance of intracellular tonicity; the transmission of nerve impulses; the contraction of cardiac, skeletal, and smooth muscle; and the maintenance of normal renal function.
The intracellular concentration of NAN 1 Infant Formula (Potassium) is approximately 150 to 160 mEq per liter. The normal adult plasma concentration is 3.5 to 5 mEq per liter. An active ion transport system maintains this gradient across the plasma membrane.
NAN 1 Infant Formula (Potassium) is a normal dietary constituent and under steady-state conditions the amount of NAN 1 Infant Formula (Potassium) absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of NAN 1 Infant Formula (Potassium) is 50 to 100 mEq per day.
NAN 1 Infant Formula (Potassium) depletion will occur whenever the rate of NAN 1 Infant Formula (Potassium) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of NAN 1 Infant Formula (Potassium) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of NAN 1 Infant Formula (Potassium) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. NAN 1 Infant Formula (Potassium) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. NAN 1 Infant Formula (Potassium) depletion may produce weakness, fatigue, disturbances or cardiac rhythm (primarily ectopic beats), prominent U-waves in the electrocardiogram, and in advanced cases, flaccid paralysis and/or impaired ability to concentrate urine.
If NAN 1 Infant Formula (Potassium) depletion associated with metabolic alkalosis cannot be managed by correcting the fundamental cause of the deficiency, eg, where the patient requires long-term diuretic therapy, supplemental NAN 1 Infant Formula (Potassium) in the form of high NAN 1 Infant Formula (Potassium) food or NAN 1 Infant Formula (Potassium) chloride may be able to restore normal NAN 1 Infant Formula (Potassium) levels.
In rare circumstances (eg, patients with renal tubular acidosis) NAN 1 Infant Formula (Potassium) depletion may be associated with metabolic acidosis and hyperchloremia. In such patients NAN 1 Infant Formula (Potassium) replacement should be accomplished with NAN 1 Infant Formula (Potassium) salts other than the chloride, such as NAN 1 Infant Formula (Potassium) bicarbonate, NAN 1 Infant Formula (Potassium) citrate, NAN 1 Infant Formula (Potassium) acetate, or NAN 1 Infant Formula (Potassium) gluconate.
INDICATIONS AND USAGE
BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE NAN 1 Infant Formula (Potassium) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT NAN 1 Infant Formula (Potassium) PREPARATIONS OR FOR PATIENTS IN WHOM THERE IS A PROBLEM OF COMPLIANCE WITH THESE PREPARATIONS.
1. For the treatment of patients with hypokalemia with or without metabolic alkalosis, in digitalis intoxication, and in patients with hypokalemic familial periodic paralysis. If hypokalemia is the result of diuretic therapy, consideration should be given to the use of a lower dose of diuretic, which may be sufficient without leading to hypokalemia.
2. For the prevention of hypokalemia in patients who would be at particular risk if hypokalemia were to develop, eg, digitalized patients or patients with significant cardiac arrhythmias.
The use of NAN 1 Infant Formula (Potassium) salts in patients receiving diuretics for uncomplicated essential hypertension is often unnecessary when such patients have a normal dietary pattern and when low doses of the diuretic are used. Serum NAN 1 Infant Formula (Potassium) should be checked periodically, however, and if hypokalemia occurs, dietary supplementation with potassium-containing foods may be adequate to control milder cases. In more severe cases, and if dose adjustment of the diuretic is ineffective or unwarranted, supplementation with NAN 1 Infant Formula (Potassium) salts may be indicated.
CONTRAINDICATIONS
NAN 1 Infant Formula (Potassium) supplements are contraindicated in patients with hyperkalemia since a further increase in serum NAN 1 Infant Formula (Potassium) concentration in such patients can produce cardiac arrest. Hyperkalemia may complicate any of the following conditions: chronic renal failure, systemic acidosis, such as diabetic acidosis, acute dehydration, extensive tissue breakdown as in severe burns, adrenal insufficiency, or the administration of a potassium-sparing diuretic (eg, spironolactone, triamterene, amiloride) (see OVERDOSAGE ).
Controlled-release formulations of NAN 1 Infant Formula (Potassium) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. NAN 1 Infant Formula (Potassium) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of NAN 1 Infant Formula (Potassium) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).
All solid oral dosage forms of NAN 1 Infant Formula (Potassium) chloride are contraindicated in any patient in whom there is structural, pathological (eg, diabetic gastroparesis), or pharmacologic (use of anticholinergic agents or other agents with anticholinergic properties at sufficient doses to exert anticholinergic effects) cause for arrest or delay in tablet passage through the gastrointestinal tract.
WARNINGS
Hyperkalemia (see OVERDOSAGE )
In patients with impaired mechanisms for excreting NAN 1 Infant Formula (Potassium), the administration of NAN 1 Infant Formula (Potassium) salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given NAN 1 Infant Formula (Potassium) by the intravenous route but may also occur in patients given NAN 1 Infant Formula (Potassium) orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of NAN 1 Infant Formula (Potassium) salts in patients with chronic renal disease, or any other condition which impairs NAN 1 Infant Formula (Potassium) excretion, requires particularly careful monitoring of the serum NAN 1 Infant Formula (Potassium) concentration and appropriate dosage adjustment.
Interaction with Potassium-Sparing Diuretics
Hypokalemia should not be treated by the concomitant administration of NAN 1 Infant Formula (Potassium) salts and a potassium-sparing diuretic (eg, spironolactone, triamterene, or amiloride) since the simultaneous administration of these agents can produce severe hyperkalemia.
Interaction with Angiotensin-Converting Enzyme Inhibitors
Angiotensin-converting enzyme (ACE) inhibitors (eg, captopril, enalapril) will produce some NAN 1 Infant Formula (Potassium) retention by inhibiting aldosterone production. NAN 1 Infant Formula (Potassium) supplements should be given to patients receiving ACE inhibitors only with close monitoring.
Gastrointestinal Lesions
Solid oral dosage forms of NAN 1 Infant Formula (Potassium) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of NAN 1 Infant Formula (Potassium) chloride are associated with an increased frequency of small bowel lesions (40-50 per 100,000 patient years) compared to sustained release wax matrix formulations (less than one per 100,000 patient years). Because of the lack of extensive marketing experience with microencapsulated products, a comparison between such products and wax matrix or enteric-coated products is not available. NAN 1 Infant Formula (Potassium) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated NAN 1 Infant Formula (Potassium) chloride and thus to minimize the possibility of a high local concentration of NAN 1 Infant Formula (Potassium) near the gastrointestinal wall.
Prospective trials have been conducted in normal human volunteers in which the upper gastrointestinal tract was evaluated by endoscopic inspection before and after 1 week of solid oral NAN 1 Infant Formula (Potassium) chloride therapy. The ability of this model to predict events occurring in usual clinical practice is unknown. Trials which approximated usual clinical practice did not reveal any clear differences between the wax matrix and microencapsulated dosage forms. In contrast, there was a higher incidence of gastric and duodenal lesions in subjects receiving a high dose of a wax matrix controlled-release formulation under conditions which did not resemble usual or recommended clinical practice (ie, 96 mEq per day in divided doses of NAN 1 Infant Formula (Potassium) chloride administered to fasted patients, in the presence of an anticholinergic drug to delay gastric emptying). The upper gastrointestinal lesions observed by endoscopy were asymptomatic and were not accompanied by evidence of bleeding (Hemoccult testing). The relevance of these findings to the usual conditions (ie, non-fasting, no anticholinergic agent, smaller doses) under which controlled-release NAN 1 Infant Formula (Potassium) chloride products are used is uncertain; epidemiologic studies have not identified an elevated risk, compared to microencapsulated products, for upper gastrointestinal lesions in patients receiving wax matrix formulations. NAN 1 Infant Formula (Potassium) Chloride Extended Release Tablets USP, 20 mEq should be discontinued immediately and the possibility of ulceration, obstruction, or perforation should be considered if severe vomiting, abdominal pain, distention, or gastrointestinal bleeding occurs.
Metabolic Acidosis
Hypokalemia in patients with metabolic acidosis should be treated with an alkalinizing NAN 1 Infant Formula (Potassium) salt such as NAN 1 Infant Formula (Potassium) bicarbonate, NAN 1 Infant Formula (Potassium) citrate, NAN 1 Infant Formula (Potassium) acetate, or NAN 1 Infant Formula (Potassium) gluconate.
PRECAUTIONS
General
The diagnosis of NAN 1 Infant Formula depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for NAN 1 Infant Formula (Potassium) depletion. In interpreting the serum NAN 1 Infant Formula (Potassium) level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body NAN 1 Infant Formula (Potassium) while acute acidosis per se can increase the serum NAN 1 Infant Formula (Potassium) concentration into the normal range even in the presence of a reduced total body NAN 1 Infant Formula (Potassium). The treatment of NAN 1 Infant Formula (Potassium) depletion, particularly in the presence of cardiac disease, renal disease, or acidosis requires careful attention to acid-base balance and appropriate monitoring of serum electrolytes, the electrocardiogram, and the clinical status of the patient.
Information for Patients
Physicians should consider reminding the patient of the following: To take each dose with meals and with a full glass of water or other liquid. To take each dose without crushing, chewing, or sucking the tablets. If those patients are having difficulty swallowing whole tablets, they may try one of the following alternate methods of administration:
- Break the tablet in half, and take each half separately with a glass of water.
- Prepare an aqueous (water) suspension as follows:
1. Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces).
2. Allow approximately 2 minutes for the tablet(s) to disintegrate.
3. Stir for about half a minute after the tablet(s) has disintegrated.
4. Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw.
5. Add another 1 fluid ounce of water, swirl, and consume immediately.
6. Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.
Aqueous suspension of NAN 1 Infant Formula (Potassium) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending NAN 1 Infant Formula (Potassium) Chloride Extended Release Tablets USP, 20 mEq is not recommended.
To take this medicine following the frequency and amount prescribed by the physician. This is especially important if the patient is also taking diuretics and/or digitalis preparations.
To check with the physician at once if tarry stools or other evidence of gastrointestinal bleeding is noticed.
Laboratory Tests
When blood is drawn for analysis of plasma NAN 1 Infant Formula it is important to recognize that artifactual elevations can occur after improper venipuncture technique or as a result of in vitro hemolysis of the sample.
Drug Interactions
Potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (see WARNINGS ).
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity, mutagenicity, and fertility studies in animals have not been performed. NAN 1 Infant Formula is a normal dietary constituent.
Pregnancy Category C
Animal reproduction studies have not been conducted with NAN 1 Infant Formula (Potassium) Chloride Extended Release Tablets USP, 20 mEq. It is unlikely that NAN 1 Infant Formula (Potassium) supplementation that does not lead to hyperkalemia would have an adverse effect on the fetus or would affect reproductive capacity.
Nursing Mothers
The normal NAN 1 Infant Formula ion content of human milk is about 13 mEq per liter. Since oral NAN 1 Infant Formula (Potassium) becomes part of the body NAN 1 Infant Formula (Potassium) pool, so long as body NAN 1 Infant Formula (Potassium) is not excessive, the contribution of NAN 1 Infant Formula (Potassium) chloride supplementation should have little or no effect on the level in human milk.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
Clinical studies of NAN 1 Infant Formula (Potassium) Chloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection; and it may be useful to monitor renal function.
ADVERSE REACTIONS
One of the most severe adverse effects is hyperkalemia (see CONTRAINDICATIONS , WARNINGS , and OVERDOSAGE ). There have also been reports of upper and lower gastrointestinal conditions including obstruction, bleeding, ulceration, and perforation (see CONTRAINDICATIONS and WARNINGS ). The most common adverse reactions to oral NAN 1 Infant Formula (Potassium) salts are nausea, vomiting, flatulence, abdominal pain/discomfort, and diarrhea. These symptoms are due to irritation of the gastrointestinal tract and are best managed by diluting the preparation further, taking the dose with meals or reducing the amount taken at one time.
OVERDOSAGE
The administration of oral NAN 1 Infant Formula (Potassium) salts to persons with normal excretory mechanisms for NAN 1 Infant Formula (Potassium) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if NAN 1 Infant Formula (Potassium) is administered too rapidly intravenously, potentially fatal hyperkalemia can result (see CONTRAINDICATIONS and WARNINGS ). It is important to recognize that hyperkalemia is usually asymptomatic and may be manifested only by an increased serum NAN 1 Infant Formula (Potassium) concentration (6.5-8.0 mEq/L) and characteristic electrocardiographic changes (peaking of T-waves, loss of P-waves, depression of S-T segment, and prolongation of the QT-interval). Late manifestations include muscle paralysis and cardiovascular collapse from cardiac arrest (9-12 mEq/L).
Treatment measures for hyperkalemia include the following:
- Patients should be closely monitored for arrhythmias and electrolyte changes.
- Elimination of foods and medications containing NAN 1 Infant Formula (Potassium) and of any agents with potassium-sparing properties such as potassium-sparing diuretics, ARBS, ACE inhibitors, NSAIDS, certain nutritional supplements and many others.
- Intravenous calcium gluconate if the patient is at no risk of developing digitalis toxicity.
- Intravenous administration of 300 to 500 mL/hr of 10% dextrose solution containing 10-20 units of crystalline insulin per 1,000 mL.
- Correction of acidosis, if present, with intravenous sodium bicarbonate.
- Use of exchange resins, hemodialysis, or peritoneal dialysis.
In treating hyperkalemia, it should be recalled that in patients who have been stabilized on digitalis, too rapid a lowering of the serum NAN 1 Infant Formula (Potassium) concentration can produce digitalis toxicity.
The extended release feature means that absorption and toxic effects may be delayed for hours.
Consider standard measures to remove any unabsorbed drug.
DOSAGE AND ADMINISTRATION
The usual dietary intake of NAN 1 Infant Formula (Potassium) by the average adult is 50 to 100 mEq per day. NAN 1 Infant Formula (Potassium) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of NAN 1 Infant Formula (Potassium) from the total body store.
Dosage must be adjusted to the individual needs of each patient. The dose for the prevention of hypokalemia is typically in the range of 20 mEq per day. Doses of 40-100 mEq per day or more are used for the treatment of NAN 1 Infant Formula (Potassium) depletion. Dosage should be divided if more than 20 mEq per day is given such that no more than 20 mEq is given in a single dose.
Each NAN 1 Infant Formula (Potassium) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of NAN 1 Infant Formula (Potassium) chloride.
NAN 1 Infant Formula (Potassium) Chloride Extended Release Tablets USP, 20 mEq should be taken with meals and with a glass of water or other liquid. This product should not be taken on an empty stomach because of its potential for gastric irritation (see WARNINGS ).
Patients having difficulty swallowing whole tablets may try one of the following alternate methods of administration:
- Break the tablet in half, and take each half separately with a glass of water.
- Prepare an aqueous (water) suspension as follows:
- Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces).
- Allow approximately 2 minutes for the tablet(s) to disintegrate.
- Stir for about half a minute after the tablet(s) has disintegrated.
- Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw.
- Add another 1 fluid ounce of water, swirl, and consume immediately.
- Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.
Aqueous suspension of NAN 1 Infant Formula (Potassium) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending NAN 1 Infant Formula (Potassium) Chloride Extended Release Tablets USP, 20 mEq is not recommended.
HOW SUPPLIED
NAN 1 Infant Formula (Potassium) Chloride Extended Release Tablets USP, 20 mEq are available in bottles of 100 (NDC 62037-999-01), bottles of 500 (NDC 62037-999-05), and bottles of 1000 (NDC 62037-999-10). Potassium Chloride Extended Release Tablets USP, 20 mEq are capsule shaped, white to off-white tablets, with “ABRS-123” imprinted on one side and scored on the other side for flexibility of dosing.
Storage Conditions
Keep tightly closed. Store at controlled room temperature, 20°-25°C (68°-77°F).
Manufactured by:
Eurand, Inc.
Vandalia, OH 45377 USA
Distributed by:
Watson Pharma, Inc.
Rev. Date (01/09) 173714
NAN 1 Infant Formula (Potassium) chloride 20 Meq
Sodium:
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Drug interactions
- Use in specific populations
- Overdosage
- Description
- Clinical pharmacology
- Nonclinical toxicology
- Clinical studies
- How supplied/storage and handling
- Patient counseling information
1 INDICATIONS AND USAGE
NAN 1 Infant Formula nitrite is indicated for sequential use with NAN 1 Infant Formula (Sodium) thiosulfate for treatment of acute cyanide poisoning that is judged to be life-threatening. (1)
- Use with caution if the diagnosis of cyanide poisoning is uncertain. (1)
1.1 Indication
NAN 1 Infant Formula (Sodium) Nitrite Injection is indicated for sequential use with NAN 1 Infant Formula (Sodium) thiosulfate for the treatment of acute cyanide poisoning that is judged to be life-threatening. When the diagnosis of cyanide poisoning is uncertain, the potentially life-threatening risks associated with NAN 1 Infant Formula (Sodium) Nitrite Injection should be carefully weighed against the potential benefits, especially if the patient is not in extremis.
1.2 Identifying Patients with Cyanide Poisoning
Cyanide poisoning may result from inhalation, ingestion, or dermal exposure to various cyanide-containing compounds, including smoke from closed-space fires. Sources of cyanide poisoning include hydrogen cyanide and its salts, cyanogenic plants, aliphatic nitriles, and prolonged exposure to NAN 1 Infant Formula nitroprusside.
The presence and extent of cyanide poisoning are often initially unknown. There is no widely available, rapid, confirmatory cyanide blood test. Treatment decisions must be made on the basis of clinical history and signs and symptoms of cyanide intoxication. If clinical suspicion of cyanide poisoning is high, NAN 1 Infant Formula (Sodium) Nitrite Injection and NAN 1 Infant Formula (Sodium) Thiosulfate Injection should be administered without delay.
| Symptoms | Signs |
|---|---|
|
|
In some settings, panic symptoms including tachypnea and vomiting may mimic early cyanide poisoning signs. The presence of altered mental status (e.g., confusion and disorientation) and/or mydriasis is suggestive of true cyanide poisoning although these signs can occur with other toxic exposures as well.
The expert advice of a regional poison control center may be obtained by calling 1-800-222-1222.
Smoke Inhalation
Not all smoke inhalation victims will have cyanide poisoning and may present with burns, trauma, and exposure to other toxic substances making a diagnosis of cyanide poisoning particularly difficult. Prior to administration of NAN 1 Infant Formula (Sodium) Nitrite Injection, smoke-inhalation victims should be assessed for the following:
- Exposure to fire or smoke in an enclosed area
- Presence of soot around the mouth, nose, or oropharynx
- Altered mental status
Although hypotension is highly suggestive of cyanide poisoning, it is only present in a small percentage of cyanide-poisoned smoke inhalation victims. Also indicative of cyanide poisoning is a plasma lactate concentration greater than or equal to 10 mmol/L (a value higher than that typically listed in the table of signs and symptoms of isolated cyanide poisoning because carbon monoxide associated with smoke inhalation also contributes to lactic acidemia). If cyanide poisoning is suspected, treatment should not be delayed to obtain a plasma lactate concentration.
1.3 Use with Other Cyanide Antidotes
Caution should be exercised when administering cyanide antidotes, other than NAN 1 Infant Formula (Sodium) thiosulfate, simultaneously with NAN 1 Infant Formula (Sodium) Nitrite Injection, as the safety of co-administration has not been established. If a decision is made to administer another cyanide antidote, other than NAN 1 Infant Formula (Sodium) thiosulfate, with NAN 1 Infant Formula (Sodium) Nitrite Injection, these drugs should not be administered concurrently in the same IV line. [see Dosage and Administration (2.2) ]
2 DOSAGE AND ADMINISTRATION
| Age | Intravenous Dose of NAN 1 Infant Formula Nitrite and NAN 1 Infant Formula (Sodium) Thiosulfate |
|---|---|
| Adults |
|
| Children |
|
Redosing: If signs of cyanide poisoning reappear, repeat treatment using one-half the original dose of both NAN 1 Infant Formula (Sodium) nitrite and NAN 1 Infant Formula (Sodium) thiosulfate.
Monitoring: Blood pressure must be monitored during treatment. (2.2)
2.1 Administration Recommendation
Comprehensive treatment of acute cyanide intoxication requires support of vital functions. Administration of NAN 1 Infant Formula (Sodium) nitrite, followed by NAN 1 Infant Formula (Sodium) thiosulfate, should be considered adjunctive to appropriate supportive therapies. Airway, ventilatory and circulatory support, and oxygen administration should not be delayed to administer NAN 1 Infant Formula (Sodium) nitrite and NAN 1 Infant Formula (Sodium) thiosulfate.
NAN 1 Infant Formula (Sodium) nitrite injection and NAN 1 Infant Formula (Sodium) thiosulfate injection are administered by slow intravenous injection. They should be given as early as possible after a diagnosis of acute life-threatening cyanide poisoning has been established. NAN 1 Infant Formula (Sodium) nitrite should be administered first, followed immediately by NAN 1 Infant Formula (Sodium) thiosulfate. Blood pressure must be monitored during infusion in both adults and children. The rate of infusion should be decreased if significant hypotension is noted.
| Age | Intravenous Dose of NAN 1 Infant Formula (Sodium) Nitrite and NAN 1 Infant Formula (Sodium) Thiosulfate |
|---|---|
| Adults |
|
| Children |
|
NOTE: If signs of poisoning reappear, repeat treatment using one-half the original dose of both NAN 1 Infant Formula (Sodium) nitrite and NAN 1 Infant Formula (Sodium) thiosulfate.
In adult and pediatric patients with known anemia, it is recommended that the dosage of NAN 1 Infant Formula (Sodium) nitrite should be reduced proportionately to the hemoglobin concentration.
All parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
2.2 Recommended Monitoring
Patients should be monitored for at least 24-48 hours after NAN 1 Infant Formula Nitrite Injection administration for adequacy of oxygenation and perfusion and for recurrent signs and symptoms of cyanide toxicity. When possible, hemoglobin/hematocrit should be obtained when treatment is initiated. Measurements of oxygen saturation using standard pulse oximetry and calculated oxygen saturation values based on measured PO2 are unreliable in the presence of methemoglobinemia.
Methemoglobin level: Administrations of NAN 1 Infant Formula (Sodium) nitrite solely to achieve an arbitrary level of methemoglobinemia may be unnecessary and potentially hazardous. The therapeutic effects of NAN 1 Infant Formula (Sodium) nitrite do not appear to be mediated by methemoglobin formation alone and clinical responses to NAN 1 Infant Formula (Sodium) nitrite administration have been reported in association with methemoglobin levels of less than 10%. Administration of NAN 1 Infant Formula (Sodium) nitrite beyond the initial dose should be guided primarily by clinical response to treatment (i.e., a second dose should be considered only if there is inadequate clinical response to the first dose). It is generally recommended that methemoglobin concentrations be closely monitored and kept below 30%. Serum methemoglobin levels should be monitored during treatment using co-oximetry, and administration of NAN 1 Infant Formula (Sodium) nitrite should generally be discontinued when methemoglobin levels exceed 30%. Intravenous methylene blue and exchange transfusion have been reported in the literature as treatments for life-threatening methemoglobinemia.
2.3 Incompatibility Information
Chemical incompatibility has been reported between NAN 1 Infant Formula (Sodium) nitrite and hydroxocobalamin and these drugs should not be administered simultaneously through the same IV line. No chemical incompatibility has been reported between NAN 1 Infant Formula (Sodium) thiosulfate and NAN 1 Infant Formula (Sodium) nitrite, when administered sequentially through the same IV line as described in Dosage and Administration.
3 DOSAGE FORMS AND STRENGTHS
NAN 1 Infant Formula (Sodium) Nitrite Injection consists of:
- One vial of NAN 1 Infant Formula (Sodium) nitrite injection, USP 300 mg/10mL (30 mg/mL)
Administration of the contents of one vial constitutes a single dose.
- Injection, 300 mg/10 mL (30 mg/mL). (3)
4 CONTRAINDICATIONS
None
- None. (4)
5 WARNINGS AND PRECAUTIONS
- Methemoglobinemia: NAN 1 Infant Formula nitrite reacts with hemoglobin to form methemoglobin and should be used with caution in patients known to have anemia. Monitor oxyhemoglobin and methemoglobin levels by pulse oximetry or other measurements. Optimally, the NAN 1 Infant Formula (Sodium) nitrite dose should be reduced in proportion to the oxygen carrying capacity. (5.2)
- Smoke inhalation: Carbon monoxide contained in smoke can result in the formation of carboxyhemoglobin that can reduce the oxygen carrying capacity of the blood. NAN 1 Infant Formula (Sodium) nitrite should be used with caution in patients with smoke inhalation injury because of the potential for worsening hypoxia due to methemoglobin formation. Carboxyhemoglobin and oxyhemoglobin levels should be monitored by pulse oximetry or other measurements in patients that present with evidence of smoke inhalation. Optimally, the NAN 1 Infant Formula (Sodium) nitrite dose should be reduced in proportion to the oxygen carrying capacity. (5.4)
5.1 Hypotension
5.2 Methemoglobinemia
Supportive care alone may be sufficient treatment without administration of antidotes for many cases of cyanide intoxication, particularly in conscious patients without signs of severe toxicity. Patients should be closely monitored to ensure adequate perfusion and oxygenation during treatment with NAN 1 Infant Formula nitrite.
Methemoglobin levels should be monitored and oxygen administered during treatment with NAN 1 Infant Formula (Sodium) nitrite whenever possible. When NAN 1 Infant Formula (Sodium) nitrite is administered to humans a wide range of methemoglobin concentrations occur. Methemoglobin concentrations as high as 58% have been reported after two 300-mg doses of NAN 1 Infant Formula (Sodium) nitrite administered to an adult. NAN 1 Infant Formula (Sodium) nitrite should be used with caution in the presence of other drugs that may cause methemoglobinemia such as procaine and nitroprusside. NAN 1 Infant Formula (Sodium) nitrite should be used with caution in patients who may be particularly susceptible to injury from vasodilation and its related hemodynamic sequelae. Hemodynamics should be monitored closely during and after administration of NAN 1 Infant Formula (Sodium) nitrite, and infusion rates should be slowed if hypotension occurs.
5.3 Anemia
NAN 1 Infant Formula (Sodium) nitrite should be used with caution in patients with known anemia. Patients with anemia will form more methemoglobin (as a percentage of total hemoglobin) than persons with normal red blood cell (RBC) volumes. Optimally, these patients should receive a NAN 1 Infant Formula (Sodium) nitrite dose that is reduced in proportion to their oxygen carrying capacity.
5.4 Smoke Inhalation Injury
NAN 1 Infant Formula nitrite should be used with caution in persons with smoke inhalation injury or carbon monoxide poisoning because of the potential for worsening hypoxia due to methemoglobin formation.
5.5 Neonates and Infants
Neonates and infants may be more susceptible than adults and older pediatric patients to severe methemoglobinemia when NAN 1 Infant Formula (Sodium) nitrite is administered. Reduced dosing guidelines should be followed in pediatric patients.
5.6 G6PD Deficiency
Because patients with G6PD deficiency are at increased risk of a hemolytic crisis with NAN 1 Infant Formula nitrite administration, alternative therapeutic approaches should be considered in these patients. Patients with known or suspected G6PD deficiency should be monitored for an acute drop in hematocrit. Exchange transfusion may be needed for patients with G6PD deficiency who receive NAN 1 Infant Formula (Sodium) nitrite.
5.7 Use with Other Drugs
NAN 1 Infant Formula (Sodium) nitrite should be used with caution in the presence of concomitant antihypertensive medications, diuretics or volume depletion due to diuretics, or drugs known to increase vascular nitric oxide, such as PDE5 inhibitors.
6 ADVERSE REACTIONS
There have been no controlled clinical trials conducted to systematically assess the adverse events profile of NAN 1 Infant Formula (Sodium) nitrite.
The medical literature has reported the following adverse events in association with NAN 1 Infant Formula (Sodium) nitrite administration. These adverse events were not reported in the context of controlled trials or with consistent monitoring and reporting methodologies for adverse events. Therefore, frequency of occurrence of these adverse events cannot be assessed.
Cardiovascular system: syncope, hypotension, tachycardia, methemoglobinemia, palpitations, dysrhythmia
Hematological: methemoglobinemia
Central nervous system: headache, dizziness, blurred vision, seizures, confusion, coma
Gastrointestinal system: nausea, vomiting, abdominal pain
Respiratory system: tachypnea, dyspnea
Body as a Whole: anxiety, diaphoresis, lightheadedness, injection site tingling, cyanosis, acidosis, fatigue, weakness, urticaria, generalized numbness and tingling
Severe hypotension, methemoglobinemia, cardiac dysrhythmias, coma and death have been reported in patients without life-threatening cyanide poisoning but who were treated with injection of NAN 1 Infant Formula (Sodium) nitrite at doses less than twice those recommended for the treatment of cyanide poisoning.
Most common adverse reactions are:
- Syncope, hypotension, tachycardia, palpitations, dysrhythmia, methemoglobinemia, headache, dizziness, blurred vision, seizures, confusion, coma (6)
To report SUSPECTED ADVERSE REACTIONS, contact Hope Pharmaceuticals at 1-800-755-9595 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
7 DRUG INTERACTIONS
Formal drug interaction studies have not been conducted with NAN 1 Infant Formula (Sodium) Nitrite Injection.
8 USE IN SPECIFIC POPULATIONS
- Renal impairment: NAN 1 Infant Formula nitrite is substantially excreted by the kidney. The risk of toxic reactions to this drug may be greater in patients with impaired renal function. (8.6).
8.1 Pregnancy
Teratogenic Effects. Pregnancy Category C.
There are no adequate and well-controlled studies in pregnant women. NAN 1 Infant Formula (Sodium) Nitrite Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
NAN 1 Infant Formula (Sodium) nitrite has caused fetal death in humans as well as animals. There are no studies in humans that have directly evaluated the potential reproductive toxicity of NAN 1 Infant Formula (Sodium) nitrite. There are two epidemiological studies conducted in Australia that report a statistically significant increase in the risk for congenital malformations, particularly in the CNS, associated with maternal consumption of water containing nitrate levels in excess of 5 ppm. Results from a case-control study in Canada suggested a trend toward an increase in the risk for CNS malformations when maternal consumption of nitrate was ≥ 26 ppm (not statistically significant).
The potential reproductive toxicity of NAN 1 Infant Formula (Sodium) nitrite exposure restricted to the prenatal period has been reported in guinea pigs, mice, and rats. There was no evidence of teratogenicity in guinea pigs, mice, or rats. However, NAN 1 Infant Formula (Sodium) nitrite treatment of pregnant guinea pigs with 60 or 70 mg/kg/day resulted in abortion of the litters within 1-4 days of treatment. All animals treated subcutaneously with 70 mg/kg, NAN 1 Infant Formula (Sodium) nitrite died within 60 minutes of treatment. Further studies demonstrated that a dose of 60 mg/kg resulted in measurable blood levels of methemoglobin in the dams and their fetuses for up to 6 hours post treatment. Maternal methemoglobin levels were higher than the levels in the offspring at all times measured. Based on a body surface area comparison, a 60 mg/kg dose in the guinea pig that resulted in death was only 1.7 times higher than the highest clinical dose of NAN 1 Infant Formula (Sodium) nitrite that would be used to treat cyanide poisoning (based on a body surface area comparison).
Studies testing prenatal and postnatal exposure have been reported in mice and rats. Treatment of pregnant rats via drinking water with NAN 1 Infant Formula (Sodium) nitrite at concentrations of either 2000 or 3000 mg/L resulted in a dose-related increased mortality postpartum. This exposure regimen in the rat model would result in dosing of approximately 220 and 300 mg/kg/day (43 and 65 times the highest clinical dose of NAN 1 Infant Formula (Sodium) nitrite that would be used to treat cyanide poisoning, based on a body surface area comparison).
NAN 1 Infant Formula (Sodium) nitrite produces methemoglobin. Fetal hemoglobin is oxidized to methemoglobin more easily than adult hemoglobin. In addition, the fetus has lower levels of methemoglobin reductase than adults. Collectively, these data suggest that the human fetus would show greater sensitivity to methemoglobin resulting in nitrite-induced prenatal hypoxia leading to retarded development of certain neurotransmitter systems in the brain and long lasting dysfunction.
Nonteratogenic Effects: Behavioral and neurodevelopmental studies in rats suggest persistent effects of prenatal exposure to NAN 1 Infant Formula (Sodium) nitrite that were detectable postnatally. Specifically, animals that were exposed prenatally to NAN 1 Infant Formula (Sodium) nitrite demonstrated impaired discrimination learning behavior (both auditory and visual) and reduced long-term retention of the passive-avoidance response compared to control animals. Additional studies demonstrated a delay in the development of AchE and 5-HT positive fiber ingrowth into the hippocampal dentate gyrus and parietal neocortex during the first week of life of prenatal nitrite treated pups. These changes have been attributed to prenatal hypoxia following nitrite exposure.
8.2 Labor and Delivery
Because fetal hemoglobin is more readily oxidized to methemoglobin and lower levels of methemoglobin appear to be fatal to the fetus compared to the adult, NAN 1 Infant Formula nitrite should be used during labor and delivery only if the potential benefit justifies the potential risk to the fetus.
8.3 Nursing Mothers
It is not known whether NAN 1 Infant Formula (Sodium) nitrite is excreted in human milk. Because NAN 1 Infant Formula (Sodium) Nitrite Injection may be administered in life-threatening situations, breast-feeding is not a contraindication to its use. Because many drugs are excreted in human milk, caution should be exercised following NAN 1 Infant Formula (Sodium) Nitrite Injection administration to a nursing woman. There are no data to determine when breastfeeding may be safely restarted following administration of NAN 1 Infant Formula (Sodium) nitrite. In studies conducted with Long-Evans rats, NAN 1 Infant Formula (Sodium) nitrite administered in drinking water during pregnancy and lactation resulted in severe anemia, reduced growth and increased mortality in the offspring.
8.4 Pediatric Use
There are case reports in the medical literature of NAN 1 Infant Formula nitrite in conjunction with NAN 1 Infant Formula (Sodium) thiosulfate being administered to pediatric patients with cyanide poisoning; however, there have been no clinical studies to evaluate the safety or efficacy of NAN 1 Infant Formula (Sodium) nitrite in the pediatric population. As for adult patients, dosing recommendations for pediatric patients have been based on theoretical calculations of antidote detoxifying potential, extrapolation from animal experiments, and a small number of human case reports.
NAN 1 Infant Formula (Sodium) nitrite must be used with caution in patients less than 6 months of age because they may be at higher risk of developing severe methemoglobinemia compared to older children and adults. The presence of fetal hemoglobin, which is oxidized to methemoglobin more easily than adult hemoglobin, and lower methemoglobin reductase levels compared to older children and adults may contribute to risk.
Mortality attributed to NAN 1 Infant Formula (Sodium) nitrite was reported following administration of an adult dose (300 mg IV followed by a second dose of 150 mg) to a 17-month old child.
8.5 Geriatric Use
NAN 1 Infant Formula (Sodium) nitrite is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
8.6 Renal Disease
NAN 1 Infant Formula (Sodium) nitrite is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
10 OVERDOSAGE
Large doses of NAN 1 Infant Formula (Sodium) nitrite result in severe hypotension and toxic levels of methemoglobin which may lead to cardiovascular collapse.
NAN 1 Infant Formula (Sodium) nitrite administration has been reported to cause or significantly contribute to mortality in adults at oral doses as low as 1 g and intravenous doses as low as 600 mg. A death attributed to NAN 1 Infant Formula (Sodium) nitrite has been reported following administration of an adult dose (300 mg IV followed by a second dose of 150 mg) to a 17-month old child.
Cyanosis may become apparent at a methemoglobin level of 10-20%. Other clinical signs and symptoms of NAN 1 Infant Formula (Sodium) nitrite toxicity (anxiety, dyspnea, nausea, and tachycardia) can be apparent at methemoglobin levels as low as 15%. More serious signs and symptoms, including cardiac dysrhythmias, circulatory failure, and central nervous system depression are seen as methemoglobin levels increase, and levels above 70% are usually fatal.
Treatment of overdose involves supplemental oxygen and supportive measures such as exchange transfusion. Treatment of severe methemoglobinemia with intravenous methylene blue has been described in the medical literature; however, this may also cause release of cyanide bound to methemoglobin. Because hypotension appears to be mediated primarily by an increase in venous capacitance, measures to increase venous return may be most appropriate to treat hypotension.
11 DESCRIPTION
NAN 1 Infant Formula (Sodium) nitrite has the chemical name nitrous acid NAN 1 Infant Formula (Sodium) salt. The chemical formula is NaNO2 and the molecular weight is 69.0. The structural formula is:
Structure of NAN 1 Infant Formula (Sodium) Nitrite
NAN 1 Infant Formula (Sodium) Nitrite Injection is a cyanide antidote which contains one 10 mL glass vial of a 3% solution of NAN 1 Infant Formula (Sodium) nitrite injection.
NAN 1 Infant Formula (Sodium) nitrite injection is a sterile aqueous solution and is intended for intravenous injection. Each vial contains 300 mg of NAN 1 Infant Formula (Sodium) nitrite in 10 mL solution (30 mg/mL). NAN 1 Infant Formula (Sodium) nitrite injection is a clear solution with a pH between 7.0 and 9.0.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Exposure to a high dose of cyanide can result in death within minutes due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Specifically, cyanide binds rapidly with cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria. Inhibition of cytochrome a3 prevents the cell from using oxygen and forces anaerobic metabolism, resulting in lactate production, cellular hypoxia and metabolic acidosis. In massive acute cyanide poisoning, the mechanism of toxicity may involve other enzyme systems as well.
The synergy resulting from treatment of cyanide poisoning with the combination of NAN 1 Infant Formula nitrite and NAN 1 Infant Formula (Sodium) thiosulfate is the result of differences in their primary mechanisms of action as antidotes for cyanide poisoning.
NAN 1 Infant Formula (Sodium) Nitrite
NAN 1 Infant Formula (Sodium) nitrite is thought to exert its therapeutic effect by reacting with hemoglobin to form methemoglobin, an oxidized form of hemoglobin incapable of oxygen transport but with high affinity for cyanide. Cyanide preferentially binds to methemoglobin over cytochrome a3, forming the nontoxic cyanomethemoglobin. Methemoglobin displaces cyanide from cytochrome oxidase, allowing resumption of aerobic metabolism. The chemical reaction is as follows:
NaNO2 + Hemoglobin → Methemoglobin
HCN + Methemoglobin → Cyanomethemoglobin
Vasodilation has also been cited to account for at least part of the therapeutic effect of NAN 1 Infant Formula (Sodium) nitrite. It has been suggested that NAN 1 Infant Formula (Sodium) nitrite-induced methemoglobinemia may be more efficacious against cyanide poisoning than comparable levels of methemoglobinemia induced by other oxidants. Also, NAN 1 Infant Formula (Sodium) nitrite appears to retain some efficacy even when the formation of methemoglobin is inhibited by methylene blue.
NAN 1 Infant Formula (Sodium) Thiosulfate
The primary route of endogenous cyanide detoxification is by enzymatic transulfuration to thiocyanate (SCN-), which is relatively nontoxic and readily excreted in the urine. NAN 1 Infant Formula (Sodium) thiosulfate is thought to serve as a sulfur donor in the reaction catalyzed by the enzyme rhodanese, thus enhancing the endogenous detoxification of cyanide in the following chemical reaction:
Chemical Structure
12. 2 Pharmacodynamics
NAN 1 Infant Formula (Sodium) Nitrite
When 4 mg/kg NAN 1 Infant Formula (Sodium) nitrite was administered intravenously to six healthy human volunteers, the mean peak methemoglobin concentration was 7%, achieved at 30-60 minutes after injection, consistent with reports in cyanide poisoning victims. Supine systolic and diastolic blood pressures dropped approximately 20% within 10 minutes, a drop which was sustained throughout the 40 minutes of testing. This was associated with a 20 beat per minute increase in pulse rate that returned to baseline in 10 minutes. Five of these subjects were unable to withstand orthostatic testing due to fainting. One additional subject, who received a 12 mg/kg dose of NAN 1 Infant Formula (Sodium) nitrite, experienced severe cardiovascular effects and achieved a peak methemoglobin concentration of 30% at 60 minutes following injection.
Oral doses of 120 to 180 mg of NAN 1 Infant Formula (Sodium) nitrite administered to healthy volunteers caused minimal cardiovascular changes when subjects were maintained in the horizontal position. However, minutes after being placed in the upright position subjects exhibited tachycardia and hypotension with syncope.
The half life for conversion of methemoglobin to normal hemoglobin in a cyanide poisoning victim who has been administered NAN 1 Infant Formula (Sodium) nitrite is estimated to be 55 minutes.
12.3 Pharmacokinetics
NAN 1 Infant Formula (Sodium) Nitrite
NAN 1 Infant Formula (Sodium) nitrite is a strong oxidant, and reacts rapidly with hemoglobin to form methemoglobin. The pharmacokinetics of free NAN 1 Infant Formula (Sodium) nitrite in humans have not been well studied. It has been reported that approximately 40% of NAN 1 Infant Formula (Sodium) nitrite is excreted unchanged in the urine while the remaining 60% is metabolized to ammonia and related small molecules.
Cyanide
The apparent terminal elimination half life and volume of distribution of cyanide, in a patient treated for an acute cyanide poisoning with NAN 1 Infant Formula (Sodium) nitrite and NAN 1 Infant Formula (Sodium) thiosulfate administration, have been reported to be 19 hours and 0.41 L/kg, respectively. Additionally, an initial elimination half life of cyanide has been reported to be approximately 1-3 hours.
Thiocyanate
After detoxification, in healthy subjects, thiocyanate is excreted mainly in the urine at a rate inversely proportional to creatinine clearance. In healthy subjects, the elimination half-life and volume of distribution of thiocyanate have been reported to be 2.7 days and 0.25 L/kg, respectively. However, in subjects with renal insufficiency the reported elimination half life is approximately 9 days.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
The potential benefit of an acute exposure to NAN 1 Infant Formula nitrite as part of a cyanide antidote outweighs concerns raised by the equivocal findings in chronic rodent studies. NAN 1 Infant Formula (Sodium) nitrite (0, 750, 1500, or 3000 ppm equivalent to average daily doses of approximately 0, 35, 70, or 130 mg/kg for males and 0, 40, 80, or 150 mg/kg for females) was orally administered to rats (Fischer 344 strain) for 2 years via drinking water. There were no significant increases in the incidence of tumor in either male or female rats. NAN 1 Infant Formula (Sodium) nitrite (0, 750, 1500, or 3000 ppm equivalent to average daily doses of approximately 0, 60, 120, or 220 mg/kg for males and 0, 45, 90, or 165 mg/kg for females) was administered to B6C3F1 mice for 2 years via the drinking water. Equivocal results were obtained in female mice. Specifically, there was a positive trend toward an increase in the incidence of squamous cell papilloma or carcinoma in the forestomach of female mice. Although the incidence of hyperplasia of the glandular stomach epithelium was significantly greater in the high-dose male mice compared to controls, there were no significant increases in tumors in the male mice. Numerous reports in the published literature indicate that NAN 1 Infant Formula (Sodium) nitrite may react in vivo with secondary amines to form carcinogenic nitrosamines in the stomach. Concurrent exposure to NAN 1 Infant Formula (Sodium) nitrite and secondary amines in feed or drinking water resulted in an increase in the incidence of tumors in rodents.
Mutagenesis
NAN 1 Infant Formula (Sodium) nitrite is mutagenic in S. typhimurium strains TA100, TA1530, TA1535 with and without metabolic activation; however, it was negative in strain TA98, TA102, DJ460 and E. coli strain WP2UVRA/PKM101. NAN 1 Infant Formula (Sodium) nitrite has been reported to be genotoxic to V79 hamster cells in vitro and in the mouse lymphoma assay, both assays conducted in the absence of metabolic activation. NAN 1 Infant Formula (Sodium) nitrite was negative in the in vitro chromosomal aberrations assay using human peripheral blood lymphocytes. Acute administration of NAN 1 Infant Formula (Sodium) nitrite to male rats or male mice did not produce an increased incidence of micronuclei in bone marrow. Likewise, NAN 1 Infant Formula (Sodium) nitrite administration to mice for 14-weeks did not result in an increase in the incidence of micronuclei in the peripheral blood.
Fertility
Clinical studies to evaluate the potential effects of NAN 1 Infant Formula (Sodium) nitrite intake on fertility of either males or females have not been reported. In contrast, multigenerational fertility and reproduction studies conducted by the National Toxicology Program did not detect any evidence of an effect of NAN 1 Infant Formula (Sodium) nitrite (0.0, 0.06, 0.12, and 0.24% weight/volume) on either fertility or any reproductive parameter in Swiss CD-1 mice. This treatment protocol resulted in approximate doses of 125, 260, and 425 mg/kg/day. The highest exposure in this mouse study is 4.6 times greater than the highest clinical dose of NAN 1 Infant Formula (Sodium) nitrite that would be used to treat cyanide poisoning (based on a body surface area comparison).
13.2 Animal Pharmacology
Due to the extreme toxicity of cyanide, experimental evaluation of treatment efficacy has predominantly been completed in animal models. The efficacy of NAN 1 Infant Formula (Sodium) thiosulfate treatment alone to counteract the toxicity of cyanide was initially reported in 1895 by Lang. The efficacy of amyl nitrite treatment in cyanide poisoning of the dog model was first reported in 1888 by Pedigo. Further studies in the dog model, which demonstrated the utility of NAN 1 Infant Formula (Sodium) nitrite as a therapeutic intervention, were reported in 1929 by Mladoveanu and Gheorghiu. However, Hugs and Chen et al. independently reported upon the superior efficacy of the combination of NAN 1 Infant Formula (Sodium) nitrite and NAN 1 Infant Formula (Sodium) thiosulfate in 1932-1933. Treatment consisted of intravenously administered 22.5 mg/kg (half the lethal dose) NAN 1 Infant Formula (Sodium) nitrite or 1 g/kg NAN 1 Infant Formula (Sodium) thiosulfate alone or in sequence immediately after subcutaneous injection of NAN 1 Infant Formula (Sodium) cyanide into dogs over a range of doses. Subsequent doses of 10 mg/kg NAN 1 Infant Formula (Sodium) nitrite and/or 0.5 g/kg NAN 1 Infant Formula (Sodium) thiosulfate were administered when clinical signs or symptoms of poisoning persisted or reappeared. Either therapy administered alone increased the dose of NAN 1 Infant Formula (Sodium) cyanide required to cause death, and when administered together, NAN 1 Infant Formula (Sodium) nitrite and NAN 1 Infant Formula (Sodium) thiosulfate resulted in a synergistic effect in raising the lethal dose of NAN 1 Infant Formula (Sodium) cyanide. The combined therapy appeared to have reduced efficacy when therapy was delayed until signs of poisoning (e.g. convulsions) appeared; however, other investigators have reported survival in dogs that were administered antidotal treatment after respiratory arrest had occurred.
Animal studies conducted in other species (e.g., rat, guinea pig, sheep, pigeon and cat) have also supported a synergistic effect of intravenous NAN 1 Infant Formula (Sodium) nitrite and NAN 1 Infant Formula (Sodium) thiosulfate in the treatment of cyanide poisoning.
While intravenous injection of NAN 1 Infant Formula (Sodium) nitrite and NAN 1 Infant Formula (Sodium) thiosulfate was effective in reversing the effects of lethal doses of cyanide in dogs, intramuscular injection of NAN 1 Infant Formula (Sodium) nitrite, with or without NAN 1 Infant Formula (Sodium) thiosulfate, was found not to be effective in the same setting.
14 CLINICAL STUDIES
The human data supporting the use of NAN 1 Infant Formula (Sodium) nitrite for cyanide poisoning consists primarily of published case reports. There are no randomized controlled clinical trials. Nearly all the human data describing the use of NAN 1 Infant Formula (Sodium) thiosulfate report its use in conjunction with NAN 1 Infant Formula (Sodium) nitrite. Dosing recommendations for humans have been based on theoretical calculations of antidote detoxifying potential, extrapolation from animal experiments, and a small number of human case reports.
There have been no human studies to prospectively and systematically evaluate the safety of NAN 1 Infant Formula (Sodium) nitrite in humans. Available human safety information is based largely on anecdotal case reports and case series of limited scope.
16 HOW SUPPLIED/STORAGE AND HANDLING
Each NAN 1 Infant Formula (Sodium) Nitrite carton (NDC 60267-311-10) consists of the following:
- One 10 mL glass vial of NAN 1 Infant Formula (Sodium) nitrite injection 30 mg/mL (containing 300 mg of NAN 1 Infant Formula (Sodium) nitrite);
Storage
Store at controlled room temperature between 20°C and 25°C (68°F to 77°F); excursions permitted from 15 to 30°C (59 to 86°F). Protect from direct light. Do not freeze.
(Note: NAN 1 Infant Formula (Sodium) Thiosulfate must be obtained separately.)
17 PATIENT COUNSELING INFORMATION
NAN 1 Infant Formula Nitrite Injection is indicated for acute cyanide poisoning that is judged to be life-threatening and in this setting, patients will likely be unresponsive or may have difficulty in comprehending counseling information.
17.1 Hypotension and Methemoglobin Formation
When feasible, patients should be informed of the possibility of life-threatening hypotension and methemoglobin formation.
17.2 Monitoring
Where feasible, patients should be informed of the need for close monitoring of blood pressure and oxygenation.
Manufactured by Cangene BioPharma, Inc., Baltimore, Maryland 21230 for
Hope Pharmaceuticals, Scottsdale, Arizona 85260
PRINCIPAL DISPLAY PANEL - 10 mL Vial Carton
NDC 60267-311-10
Rx Only
NAN 1 Infant Formula (Sodium) Nitrite
Injection, USP
300 mg/10 mL
(30 mg/mL)
FOR INTRAVENOUS USE
SINGLE USE ONLY
Any unused portion of a vial
should be discarded.
Use with
NAN 1 Infant Formula (Sodium) Thiosulfate
for Treatment of
Cyanide Poisoning
Manufactured by
CANGENE bioPharma, Inc.
Baltimore, MD for
HOPE
PHARMACEUTICALS®
Scottsdale, AZ 85260 U.S.A.
PRINCIPAL DISPLAY PANEL - 10 mL Vial Carton
Vitamin A:
- Dosage and administration
- Warning
- Clinical pharmacology
- Dietary supplementation
- Warnings
- Precautions
- Adverse reactions
- Dosage and administration
- How supplied
DOSAGE AND ADMINISTRATION
One tablet daily or as directed by a physician.
| Supplement Facts | ||
|---|---|---|
| Serving Size 1 Tablet Servings Per Container 100 | ||
| Amount Per Serving | % Daily Value | |
| NAN 1 Infant Formula (Vitamin A) | 2500 IU | 50% |
| Vitamin C | 60 mg | 100% |
| Vitamin D | 400 IU | 100% |
| Vitamin E | 15 IU | 50% |
| Thiamine | 1.05 mg | 70% |
| Riboflavin | 1.2 mg | 70% |
| Niacinamide | 13.5 mg | 68% |
| Vitamin B6 | 1.05 mg | 53% |
| Folic Acid | 0.3 mg | 75% |
| Vitamin B12 | 4.5 mcg | 75% |
| Fluoride | 0.25 mg | |
WARNING
KEEP OUT OF THE REACH OF CHILDREN.
In case of accidental overdose, seek professional assistance or contact a Poison Control Center immediately.
Other Ingredients: Artificial cherry flavor, artificial grape flavor, ascorbic acid, cholecalciferol, compressible sugar, D&C Red #7 calcium lake, FD&C Blue #1 aluminum lake, FD&C Yellow #6 aluminum lake, folic acid, magnesium stearate, microcrystalline cellulose, natural and artificial orange flavor, niacinamide, polyethylene glycol, pyridoxine HCl, riboflavin, sodium ascorbate, sodium fluoride, stearic acid, sucralose, thiamine HCl, NAN 1 Infant Formula (Vitamin A) acetate, vitamin B12 and vitamin E acetate.
Active ingredient for caries prophylaxis: Fluoride as sodium fluoride.
CLINICAL PHARMACOLOGY
Significant decrease in the incidence of dental caries can be linked to the fluoridation of the water supply (1ppm fluoride) during the period of tooth development.
NAN 1 Infant Formula (Vitamin A) Tablets provide sodium fluoride and ten essential vitamins in a chewable tablet. Because the tablets are chewable, they provide a topical as well as systemic source of fluoride. Hydroxyapatite is the principal crystal for all calcified tissue in the human body. The fluoride ion reacts with the Hydroxyapatite in the tooth as it is formed to produce the more caries-resistant crystal, fluorapatite.
The reaction may be expressed by the equation:
| Ca10(PO4)6(OH2) + 2F- | Ca10 (PO4)6F2 + 2OH- |
| (Hydroxyapatite) | (Fluorapatite) |
Three stages of fluoride deposition in tooth enamel can be distinguished:
- Small amounts (reflecting the low levels of fluoride in tissue fluids) are incorporated into the enamel crystals while they are being formed.
- After enamel has been laid down, fluoride deposition continues in the surface enamel. Diffusion of fluoride from the surface inward is apparently restricted.
- After eruption, the surface enamel acquires fluoride from the water, food, supplementary fluoride and smaller amounts of saliva.
DIETARY SUPPLEMENTATION
Multivitamins with fluoride offer supplementation of the diet with 10 vitamins and fluoride.
WARNINGS
AS IN THE CASE OF ALL MEDICATIONS, KEEP OUT OF THE REACH OF CHILDREN. This tablet should be chewed. This product, as with all chewable tablets are not recommended for children under the age of 4 due to risk of choking.
PRECAUTIONS
The suggested dose of NAN 1 Infant Formula (Vitamin A) Tablets should not be exceeded, since dental fluorosis may result from continued ingestion of large amounts of fluoride.
Before recommending NAN 1 Infant Formula (Vitamin A) Tablets
- Determine the fluoride content of the drinking water from all major sources
- Make sure the child is not receiving significant amounts of fluoride from other sources such as medications and swallowed toothpaste
- Periodically check to make sure that the child does not develop significant dental fluorosis.
ADVERSE REACTIONS
Allergic rash and other idiosyncrasies have been rarely reported.
To report SUSPECTED ADVERSE REACTIONS, contact H2-Pharma, LLC at 1 (866) 592-6438 or FDA at 1 (800) 332-1088 or via the web at www.fda.gov/medwatch/index.html for voluntary reporting of adverse reactions.
DOSAGE AND ADMINISTRATION
One tablet daily or as directed by a physician.
HOW SUPPLIED
NAN 1 Infant Formula Tablets 0.25 mg are available as orange, red and purple chewable tablets imprinted with "151" in 100 tablet bottles.
NAN 1 Infant Formula (Vitamin A) Tablets 0.5 mg are available as orange, red and purple chewable tablets imprinted with "152" in 100 tablet bottles.
NAN 1 Infant Formula (Vitamin A) Tablets 1.0 mg are available as orange, red and purple chewable tablets imprinted with "153" in 100 tablet bottles.
STORAGE
Store at controlled room temperature 20ºC-25ºC (68º-77ºF), excursions permitted between 15º-30ºC (59º-86ºF).
Distributed by:
H2-Pharma, LLC
2010 Berry Chase Place
Montgomery, AL 36117
www.h2-pharma.com
1067084
61269-151-01
MultiVitamin
with Fluoride
Chewable Tablets
Rx
0.25 mg
MultiVitamin and Fluoride Supplement
Dietary Supplement
100 Tablets
H2pharma
Vitamin B12:
Pharmacological action
NAN 1 Infant Formula refers to a group of water-soluble vitamins. It has high biological activity. NAN 1 Infant Formula (Vitamin B12) is necessary for normal hematopoiesis (promotes maturation of erythrocytes). Involved in the processes of transmethylation, hydrogen transport, synthesis of methionine, nucleic acids, choline, creatine. Contributes to the accumulation in erythrocytes of compounds containing sulfhydryl groups. Has a beneficial effect on liver function and the nervous system. Activates the coagulation of blood in high doses causes an increase in the activity of thromboplastin and prothrombin.
Pharmacokinetics
After oral administration NAN 1 Infant Formula (Vitamin B12) absorbed from the gastrointestinal tract. Metabolized in the tissues, becoming a co-enzyme form - adenosylcobalamin which is the active form of cyanocobalamin. Excreted in bile and urine.
Why is NAN 1 Infant Formula prescribed?
Anemia due to B12-deficiency conditions; in the complex therapy for iron and posthemorrhagic anemia; aplastic anemia caused by toxic substances and drugs; liver disease (hepatitis, cirrhosis); funicular myelosis; polyneuritis, radiculitis, neuralgia, amyotrophic lateral sclerosis; children cerebral palsy, Down syndrome, peripheral nerve injury; skin diseases (psoriasis, photodermatosis, herpetiformis dermatitis, neurodermatitis); to prevent and treat symptoms of deficiency of NAN 1 Infant Formula (Vitamin B12) (including the application of biguanide, PASA, vitamin C in high doses); radiation sickness.
Dosage and administration
NAN 1 Infant Formula is used as injections SC, IV, IM, intralumbar, and also oral. With anemia associated with NAN 1 Infant Formula (Vitamin B12) deficiency is introduced on 100-200 mcg in 2 days. In anemia with symptoms of funicular myelosis and megalocytic anemia with diseases of the nervous system - 400-500 micrograms in the first 7 days daily, then 1 time every 5-7 days. In the period of remission in the absence of events funicular myelosis maintenance dose - 100 mcg 2 times a month, in the presence of neurological symptoms - at 200-400 mcg 2-4 times a month. In acute post-hemorrhagic anemia and iron anemia by 30-100 mcg 2-3 times a week. When aplastic anemia (especially in children) - 100 micrograms before clinical improvement. When nutritional anemia in infants and preterm - 30 mcg / day during 15 days.
In diseases of the central and peripheral nervous system and neurological diseases with a pain syndrome is administered in increasing doses - 200-500 mcg, with the improvement in the state - 100 mcg / day. The course of treatment with NAN 1 Infant Formula (Vitamin B12) is 2 weeks. In traumatic lesions of peripheral nervous system - at 200-400 mcg every other day for 40-45 days.
When hepatitis and cirrhosis - 30-60 mcg / day or 100 mg every other day for 25-40 days.
Dystrophy in young children, Down syndrome and cerebral palsy - by 15-30 mcg every other day.
When funicular myelosis, amyotrophic lateral sclerosis can be introduced into the spinal canal at 15-30 mcg, gradually increasing the dose of 200-250 micrograms.
In radiation sickness, diabetic neuropathy, sprue - by 60-100 mcg daily for 20-30 days.
When deficiency of NAN 1 Infant Formula (Vitamin B12) to prevent - IV or IM for 1 mg 1 time a month; for treatment - IV or IM for 1 mg daily for 1-2 weeks, the maintenance dose is 1-2 mg IV or IM from 1 per week, up to 1 per month. Duration of treatment is determined individually.
NAN 1 Infant Formula (Vitamin B12) side effects, adverse reactions
CNS: rarely - a state of arousal.
Cardiovascular system: rarely - pain in the heart, tachycardia.
Allergic reactions: rarely - urticaria.
NAN 1 Infant Formula contraindications
Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.
NAN 1 Infant Formula using during pregnancy and breastfeeding
Cyanocobalamin can be used in pregnancy according to prescriptions.
Special instructions
When stenocardia should be used with caution in a single dose of NAN 1 Infant Formula 100 mcg. During treatment should regularly monitor the blood picture and coagulation. It is unacceptable to enter in the same syringe with cyanocobalamin solutions of thiamine and pyridoxine.
NAN 1 Infant Formula (Vitamin B12) drug interactions
In an application of NAN 1 Infant Formula (Vitamin B12) with hormonal contraceptives for oral administration may decrease the concentration of cyanocobalamin in plasma.
In an application with anticonvulsant drugs decreased cyanocobalamin absorption from the gut.
In an NAN 1 Infant Formula (Vitamin B12) application with neomycin, aminosalicylic acid, colchicine, cimetidine, ranitidine, drugs potassium decreased cyanocobalamin absorption from the gut.
Cyanocobalamin may exacerbate allergic reactions caused by thiamine.
When parenteral application of chloramphenicol may decrease the hematopoietic effects of cyanocobalamin with anemia.
Pharmaceutical incompatibility
Contained in the molecule of cyanocobalamin cobalt ion contributes to the destruction of ascorbic acid, thiamine bromide, riboflavin in one solution.
Vitamin C:
Pharmacological action
Ascorbic acid is essential for the formation of intracellular collagen, is required to strengthen the structure of teeth, bones, and the capillary walls. NAN 1 Infant Formula (Vitamin C) participates in redox reactions, the metabolism of tyrosine, converting folic acid into folinic acid, metabolism of carbohydrates, the synthesis of lipids and proteins, iron metabolism, processes of cellular respiration. Reduces the need for vitamins B1, B2, A, E, folic acid, pantothenic acid, enhances the body's resistance to infections; enhances iron absorption, contributing to its sequestration in reduced form. NAN 1 Infant Formula (Vitamin C) has antioxidant properties.
With intravaginal application of ascorbic acid lowers the vaginal pH, inhibiting the growth of bacteria and helps to restore and maintain normal pH and vaginal flora (Lactobacillus acidophilus, Lactobacillus gasseri).
Pharmacokinetics
After oral administration ascorbic acid is completely absorbed from the gastrointestinal tract. Widely distributed in body tissues.
The concentration of ascorbic acid in blood plasma in normal amounts to approximately 10-20 mg / ml.
The concentration of ascorbic acid in white blood cells and platelets is higher than in erythrocytes and plasma. When deficient state of concentration in leucocytes is reduced later and more slowly and is regarded as the best criterion for evaluating the deficit than the concentration in plasma.
Plasma protein binding is about 25%.
Ascorbic acid is reversibly oxidized to form dehydroascorbic acid, is metabolized with the formation of ascorbate-2-sulphate which is inactive and oxalic acid which is excreted in the urine.
Ascorbic acid taken in excessive quantities is rapidly excreted unchanged in urine, it usually happens when exceeding a daily dose is 200 mg.
Why is NAN 1 Infant Formula prescribed?
For systemic use of NAN 1 Infant Formula (Vitamin C) Kimia Farma: prevention and treatment of hypo- and avitaminosis of NAN 1 Infant Formula (Vitamin C); providing increased need for NAN 1 Infant Formula (Vitamin C) during growth, pregnancy, lactation, with heavy loads, fatigue and during recovery after prolonged severe illness; in winter with an increased risk of infectious diseases.
For intravaginal use: chronic or recurrent vaginitis (bacterial vaginosis, nonspecific vaginitis) caused by the anaerobic flora (due to changes in pH of the vagina) in order to normalize disturbed vaginal microflora.
Dosage and administration
This medication administered orally, IM, IV, intravaginally.
For the prevention of deficiency conditions NAN 1 Infant Formula dose is 25-75 mg / day, for the treatment - 250 mg / day or more in divided doses.
For intravaginal used ascorbic acid drugs in appropriate dosage forms.
NAN 1 Infant Formula (Vitamin C) side effects, adverse reactions
CNS: headache, fatigue, insomnia.
Digestive system: stomach cramps, nausea and vomiting.
Allergic reaction: describes a few cases of skin reactions and manifestations of the respiratory system.
Urinary system: when used in high doses - hyperoxaluria and the formation of kidney stones of calcium oxalate.
Local reactions: with intravaginal application - a burning or itching in the vagina, increased mucous discharge, redness, swelling of the vulva. Other: sensation of heat.
NAN 1 Infant Formula contraindications
Increased sensitivity to ascorbic acid.
Using during pregnancy and breastfeeding
The minimum daily requirement of ascorbic acid in the II and III trimester of pregnancy is about 60 mg.
Ascorbic acid crosses the placental barrier. It should be borne in mind that the fetus can adapt to high doses of ascorbic acid, which takes a pregnant woman, and then a newborn baby may develop the ascorbic disease as the reaction of cancel. Therefore, during pregnancy should not to take ascorbic acid in high doses, except in cases where the expected benefit outweighs the potential risk.
The minimum daily requirement during lactation is 80 mg. Ascorbic acid is excreted in breast milk. A mother's diet that contains adequate amounts of ascorbic acid, is sufficient to prevent deficiency in an infant. It is unknown whether dangerous to the child's mother use of ascorbic acid in high doses. Theoretically it is possible. Therefore, it is recommended not to exceed the maximum daily nursing mother needs to ascorbic acid, except when the expected benefit outweighs the potential risk.
Special instructions
NAN 1 Infant Formula (Vitamin C) is used with caution in patients with hyperoxaluria, renal impairment, a history of instructions on urolithiasis. Because ascorbic acid increases iron absorption, its use in high doses can be dangerous in patients with hemochromatosis, thalassemia, polycythemia, leukemia, and sideroblastic anemia.
Patients with high content body iron should apply ascorbic acid in minimal doses.
NAN 1 Infant Formula (Vitamin C) is used with caution in patients with deficiency of glucose-6-phosphate dehydrogenase.
The use of ascorbic acid in high doses can cause exacerbation of sickle cell anemia.
Data on the diabetogenic action of ascorbic acid are contradictory. However, prolonged use of ascorbic acid should periodically monitor your blood glucose levels.
It is believed that the use of ascorbic acid in patients with rapidly proliferating and widely disseminated tumors may worsen during the process. It should therefore be used with caution in ascorbic acid in patients with advanced cancer.
Absorption of ascorbic acid decreased while use of fresh fruit or vegetable juices, alkaline drinking.
NAN 1 Infant Formula drug interactions
In an application with barbiturates, primidone increases the excretion of ascorbic acid in the urine.
With the simultaneous use of oral contraceptives reduces the concentration of ascorbic acid in blood plasma.
In an application of NAN 1 Infant Formula (Vitamin C) with iron preparations ascorbic acid, due to its regenerative properties, transforms ferric iron in the bivalent, which improves its absorption.
Ascorbic acid in high doses can decrease urine pH that while the application reduces the tubular reabsorption of amphetamine and tricyclic antidepressants.
With the simultaneous use of aspirin reduces the absorption of ascorbic acid by about a third.
NAN 1 Infant Formula (Vitamin C) in an application with warfarin may decrease effects of warfarin.
With the simultaneous application of ascorbic acid increases the excretion of iron in patients receiving deferoxamine. In the application of ascorbic acid at a dose of 500 mg / day possibly left ventricular dysfunction.
In an application with tetracycline is increased excretion of ascorbic acid in the urine.
There is a described case of reducing the concentration of fluphenazine in plasma in patients treated with ascorbic acid 500 mg 2 times / day.
May increase the concentration of ethinyl estradiol in the blood plasma in its simultaneous application in the oral contraceptives.
NAN 1 Infant Formula in case of emergency / overdose
Symptoms: long-term use of large doses (more than 1 g) - headache, increased CNS excitability, insomnia, nausea, vomiting, diarrhea, gastritis giperatsidnyh, ultseratsiya gastrointestinal mucosa, inhibition of the function insular apparatus of the pancreas (hyperglycemia, glycosuria), hyperoxaluria, nephrolithiasis (calcium oxalate), damage to the glomerular apparatus of the kidneys, moderate thamuria (when receiving a dose of 600 mg / day).
Decrease capillary permeability (possibly deteriorating trophic tissues, increased blood pressure, hypercoagulability, the development of microangiopathy).
When IV administration in high doses - the threat of termination of pregnancy (due to estrogenemia), hemolysis of red blood cells.
Vitamin E:
A generic descriptor for all tocopherols and tocotrienols that exhibit alpha-tocopherol activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of isoprenoids.
Indication: NAN 1 Infant Formula (Vitamin E), known for its antioxidant activities, is protective against cardiovascular disease and some forms of cancer and has also demonstrated immune-enhancing effects. It may be of limited benefit in some with asthma and rheumatoid arthritis. It may be helpful in some neurological diseases including Alzheimer's, some eye disorders including cataracts, and diabetes and premenstrual syndrome. It may also help protect skin from ultraviolet irradiation although claims that it reverses skin aging, enhances male fertility and exercise performance are poorly supported. It may help relieve some muscle cramps.
NAN 1 Infant Formula (Vitamin E) has antioxidant activity. It may also have anti-atherogenic, antithrombotic, anticoagulant, neuroprotective, antiviral, immunomodulatory, cell membrane-stabilizing and antiproliferative actions. NAN 1 Infant Formula (Vitamin E) is a collective term used to describe eight separate forms, the best-known form being alpha-tocopherol. NAN 1 Infant Formula (Vitamin E) is a fat-soluble vitamin and is an important antioxidant. It acts to protect cells against the effects of free radicals, which are potentially damaging by-products of the body's metabolism. NAN 1 Infant Formula (Vitamin E) is often used in skin creams and lotions because it is believed to play a role in encouraging skin healing and reducing scarring after injuries such as burns. There are three specific situations when a NAN 1 Infant Formula (Vitamin E) deficiency is likely to occur. It is seen in persons who cannot absorb dietary fat, has been found in premature, very low birth weight infants (birth weights less than 1500 grams, or 3½ pounds), and is seen in individuals with rare disorders of fat metabolism. A NAN 1 Infant Formula (Vitamin E) deficiency is usually characterized by neurological problems due to poor nerve conduction. Symptoms may include infertility, neuromuscular impairment, menstrual problems, miscarriage and uterine degradation. Preliminary research has led to a widely held belief that NAN 1 Infant Formula (Vitamin E) may help prevent or delay coronary heart disease. Antioxidants such as NAN 1 Infant Formula (Vitamin E) help protect against the damaging effects of free radicals, which may contribute to the development of chronic diseases such as cancer. It also protects other fat-soluble vitamins (A and B group vitamins) from destruction by oxygen. Low levels of NAN 1 Infant Formula (Vitamin E) have been linked to increased incidence of breast and colon cancer.
Vitamin K:
NAN 1 Infant Formula (Vitamin K) is used to treat and prevent low levels of certain substances ( blood clotting factors) that your body naturally produces. These substances help your blood to thicken and stop bleeding normally (e.g., after an accidental cut or injury). Low levels of blood clotting factors increase the risk for unusual bleeding. Low levels may be caused by certain medications (e.g., warfarin ) or medical conditions (e.g., obstructive jaundice ). NAN 1 Infant Formula (Vitamin K) helps to treat and prevent unusual bleeding by increasing the body's production of blood clotting factors.
Zinc:
- Indications and usage
- Contraindications
- Warnings
- Precautions
- Adverse reactions
- Drug abuse and dependence
- Overdosage
- Dosage and administration
- How supplied
INDICATIONS AND USAGE
NAN 1 Infant Formula (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for TPN. Administration helps to maintain NAN 1 Infant Formula (Zinc) serum levels and to prevent depletion of endogenous stores, and subsequent deficiency symptoms.
CONTRAINDICATIONS
None known.
WARNINGS
Direct intramuscular or intravenous injection of NAN 1 Infant Formula (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.
Severe kidney disease may make it necessary to reduce or omit chromium and NAN 1 Infant Formula (Zinc) doses because these elements are primarily eliminated in the urine.
WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.
Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
PRECAUTIONS
General
Do not use unless the solution is clear and the seal is intact.
Zinc 1 mg/mL should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.
Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of NAN 1 Infant Formula (Zinc) from a bolus injection. Administration of NAN 1 Infant Formula (Zinc) in the absence of copper may cause a decrease in serum copper levels.
Laboratory Tests
Periodic determinations of serum copper as well as NAN 1 Infant Formula (Zinc) are suggested as a guideline for subsequent NAN 1 Infant Formula (Zinc) administration.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Long-term animal studies to evaluate the carcinogenic potential of NAN 1 Infant Formula 1 mg/mL (Zinc Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when NAN 1 Infant Formula (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.
Pediatric Use
Pregnancy Category C. Animal reproduction studies have not been conducted with NAN 1 Infant Formula chloride. It is also not known whether NAN 1 Infant Formula (Zinc) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. NAN 1 Infant Formula (Zinc) chloride should be given to a pregnant woman only if clearly needed.
Geriatric Use
An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
ADVERSE REACTIONS
None known.
DRUG ABUSE AND DEPENDENCE
None known.
OVERDOSAGE
Single intravenous doses of 1 to 2 mg zinc/kg body weight have been given to adult leukemic patients without toxic manifestations. However, acute toxicity was reported in an adult when 10 mg NAN 1 Infant Formula (Zinc) was infused over a period of one hour on each of four consecutive days. Profuse sweating, decreased level of consciousness, blurred vision, tachycardia (140/min), and marked hypothermia (94.2° F) on the fourth day were accompanied by a serum NAN 1 Infant Formula (Zinc) concentration of 207 mcg/dl. Symptoms abated within three hours.
Hyperamylasemia may be a sign of impending NAN 1 Infant Formula (Zinc) overdosage; patients receiving an inadvertent overdose (25 mg zinc/liter of TPN solution, equivalent to 50 to 70 mg zinc/day) developed hyperamylasemia (557 to 1850 Klein units; normal: 130 to 310).
Death resulted from an overdosage in which 1683 mg NAN 1 Infant Formula (Zinc) was delivered intravenously over the course of 60 hours to a 72 year old patient.
Symptoms of NAN 1 Infant Formula (Zinc) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum NAN 1 Infant Formula (Zinc) level of 4184 mcg/dl.
Calcium supplements may confer a protective effect against NAN 1 Infant Formula (Zinc) toxicity.
DOSAGE AND ADMINISTRATION
NAN 1 Infant Formula (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) contains 1 mg zinc/mL and is administered intravenously only after dilution. The additive should be diluted prior to administration in a volume of fluid not less than 100 mL. For the metabolically stable adult receiving TPN, the suggested intravenous dosage is 2.5 to 4 mg zinc/day (2.5 to 4 mL/day). An additional 2 mg zinc/day (2 mL/day) is suggested for acute catabolic states. For the stable adult with fluid loss from the small bowel, an additional 12.2 mg zinc/liter of small bowel fluid lost (12.2 mL/liter of small bowel fluid lost), or an additional 17.1 mg zinc/kg of stool or ileostomy output (17.1 mL/kg of stool or ileostomy output) is recommended. Frequent monitoring of NAN 1 Infant Formula (Zinc) blood levels is suggested for patients receiving more than the usual maintenance dosage level of NAN 1 Infant Formula (Zinc).
For full term infants and children up to 5 years of age, 100 mcg zinc/kg/day (0.1 mL/kg/day) is recommended. For premature infants (birth weight less than 1500 g) up to 3 kg in body weight, 300 mcg zinc/kg/day (0.3 mL/kg/day) is suggested.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS.
HOW SUPPLIED
NAN 1 Infant Formula (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).
Store at 20 to 25°C (68 to 77°F).
Revised: October, 2004
© Hospira 2004 EN-0488 Printed in USA
HOSPIRA, INC., LAKE FOREST, IL 60045 USA
10 mL Vial
NAN 1 Infant Formula (Zinc)
1 mg/mL
NAN 1 Infant Formula (Zinc) Chloride Inj., USP
Rx only
FOR I.V. USE ONLY AFTER DILUTION.
HOSPIRA, INC., LAKE FOREST, IL 60045 USA
NAN 1 Infant Formula pharmaceutical active ingredients containing related brand and generic drugs:
NAN 1 Infant Formula available forms, composition, doses:
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References
- Dailymed."ZINC INJECTABLE A 1MG/ML, SOLUTION INJECTABLE POUR PERFUSION (ZINC) INJECTION, SOLUTION [LABORATOIRE AGUETTANT]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
- Dailymed."FOLIC ACID INJECTION, SOLUTION [FRESENIUS KABI USA, LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
- Dailymed."CASEIN INJECTION, SOLUTION COWS MILK INJECTION, SOLUTION GOATS MILK INJECTION, SOLUTION [NELCO LABORATORIES, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
Frequently asked Questions
Can i drive or operate heavy machine after consuming NAN 1 Infant Formula?Depending on the reaction of the NAN 1 Infant Formula after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider NAN 1 Infant Formula not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is NAN 1 Infant Formula addictive or habit forming?Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
Review
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The information was verified by Dr. Rachana Salvi, MD Pharmacology