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DRUGS & SUPPLEMENTS
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Calcium (Calcium Phosphate Dibasic):
Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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)
The recommended initial dose of Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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)
Capsule: 667 mg Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate capsule.
- Capsule: 667 mg Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate capsule. (3)
Patients with hypercalcemia.
- Hypercalcemia. (4)
- Treat mild hypercalcemia by reducing or interrupting Life Guard H E Pws ) acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate. (5.1)
- Hypercalcemia may aggravate digitalis toxicity. (5.2)
Patients with end stage renal disease may develop hypercalcemia when treated with Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)), including Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate. Avoid the use of Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) supplements, including Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) based nonprescription antacids, concurrently with Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate.
An overdose of Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) levels twice weekly. Should hypercalcemia develop, reduce the Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate; all cases resolved upon lowering the dose or discontinuing treatment.
Maintain the serum calcium-phosphorus (Ca x P) product below 55 mg2/dL2.
Hypercalcemia may aggravate digitalis toxicity.
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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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
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, Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate has been generally well tolerated.
Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate N=167 N (%) | 3 month, open label study of Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate N=98 N (%) | Double blind, placebo-controlled, cross-over study of liquid Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate N=69 | |
Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) concentration could reduce the incidence and severity of Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate-induced hypercalcemia. Isolated cases pruritus have been reported, which may represent allergic reactions.
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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate: dizziness, edema, and weakness.
The drug interaction of Life Guard H E Pws ) acetate is characterized by the potential of Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.
There are no empirical data on avoiding drug interactions between Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate and most concomitant drugs. When administering an oral medication with Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate or consider monitoring blood levels of the drug. (7)
In a study of 15 healthy subjects, a co-administered single dose of 4 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.
Pregnancy Category C:
Life Guard H E Pws ) acetate capsules contains Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate. Animal reproduction studies have not been conducted with Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate, and there are no adequate and well controlled studies of Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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. Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate treatment, as recommended, is not expected to harm a fetus if maternal Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) levels are properly monitored during and following treatment.
The effects of Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate on labor and delivery are unknown.
Life Guard H E Pws ) Acetate Capsules contains Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate and is excreted in human milk. Human milk feeding by a mother receiving Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate is not expected to harm an infant, provided maternal serum Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) levels are appropriately monitored.
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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.
Administration of Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].
Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate acts as a phosphate binder. Its chemical name is Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)), 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.
Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) Acetate Capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure.
Patients with ESRD retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum Life Guard H E Pws ) resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.
Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.
Orally administered Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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.
No carcinogenicity, mutagenicity, or fertility studies have been conducted with Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate.
Effectiveness of Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 |
Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) (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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate is shown in the Table 3.
* ANOVA of Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate vs. placebo after 2 weeks of treatment. † Values expressed as mean ± SEM. | ||||
Parameter | Pre-Study | Post-Treatment | p-value* | |
Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) Acetate | Placebo | |||
Phosphorus (mg/dL)† | 7.3 ± 0.18 | 5.9 ± 0.24 | 7.8 ± 0.22 | <0.01 |
Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) (mg/dL)† | 8.9 ± 0.11 | 9.5 ± 0.13 | 8.8 ± 0.12 | <0.01 |
Overall, 2 weeks of treatment with Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.
Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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).
Inform patients to take Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) 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 Life Guard H E Pws (Calcium (Calcium Phosphate Dibasic)) acetate capsules.
Distr. by: West-Ward
Pharmaceuticals Corp.
Eatontown, NJ 07724
10003705/05
Revised April 2016
Dextrose:
70% Life Guard H E Pws (Dextrose) Injection USP is indicated as a caloric component in a parenteral nutrition regimen. 70% Life Guard H E Pws (Dextrose) Injection USP is used with an appropriate protein (nitrogen) source in the prevention of nitrogen loss or in the treatment of negative nitrogen balance in patients where: (1) the alimentary tract cannot or should not be used, (2) gastrointestinal absorption of protein is impaired, or (3) metabolic requirements for protein are substantially increased, as with extensive burns.
The infusion of 70% Life Guard H E Pws (Dextrose) Injection USP is contraindicated in patients having intracranial or intraspinal hemorrhage, in patients who are severely dehydrated, in patients who are anuric, and in patients in hepatic coma.
Solutions containing Life Guard H E Pws (Dextrose) may be contraindicated in patients with hypersensitivity to corn products.
This injection is for compounding only, not for direct infusion.
Dilute before use to a concentration which will, when administered with an amino acid (nitrogen) source, result in an appropriate calorie to gram of nitrogen ratio and which has an osmolarity consistent with the route of administration.
Unless appropriately diluted, the infusion of hypertonic Life Guard H E Pws (Dextrose) injection into a peripheral vein may result in vein irritation, vein damage, and thrombosis. Strongly hypertonic nutrient solutions should only be administered through an indwelling intravenous catheter with the tip located in a large central vein such as the superior vena cava.
Use of 70% Life Guard H E Pws (Dextrose) Injection USP to prepare parenteral nutritional admixtures may be incompatible with other components, especially calcium and phosphate salts and lipid emulsions. Incompatibility of admixed components can produce precipitates which may cause particulate emboli. Use 70% Life Guard H E Pws (Dextrose) Injection USP only to prepare formulations that are known to be stable: refer to standard texts for further information.
The administration of intravenous solutions can cause fluid and/or solute overload resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentration.
WARNING: 70% Life Guard H E Pws (Dextrose) Injection USP 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 µg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
Prolonged infusion of isotonic or hypotonic Life Guard H E Pws (Dextrose) in water may increase the volume of extracellular fluid and cause water intoxication.
Solutions containing Life Guard H E Pws (Dextrose) without electrolytes should not be administered simultaneously with blood through the same infusion set because of the possibility of agglomeration.
Excessive administration of potassium-free Life Guard H E Pws (Dextrose) solutions may result in significant hypokalemia. Serum potassium levels should be maintained and potassium supplemented as required.
In very low birth weight infants, excessive or rapid administration of Life Guard H E Pws (Dextrose) injection may result in increased serum osmolality and possible intracerebral hemorrhage.
This solution should be used with care in patients with hypervolemia, renal insufficiency, urinary tract obstruction, or impending or frank cardiac decompensation.
Solutions containing Life Guard H E Pws should be used with caution in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason.
Essential electrolytes, minerals, and vitamins should be supplied as needed.
Hypokalemia may develop during parenteral administration of hypertonic Life Guard H E Pws (Dextrose) solutions. Sufficient amounts of potassium should be added to Life Guard H E Pws (Dextrose) solutions administered to fasting patients with good renal function, especially those on digitalis therapy.
To minimize the risk of possible incompatibilities arising from mixing this solution with other additives that may be prescribed, the final infusate should be inspected for cloudiness or precipitation immediately after mixing, prior to administration, and periodically during administration. See WARNINGS .
Do not use plastic container in series connection.
If administration of 70% Life Guard H E Pws (Dextrose) Injection USP after admixture or dilution is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result. If administration is not controlled by a pumping device, refrain from applying excessive pressure (>300mmHg) causing distortion to the container such as wringing or twisting. Such handling could result in breakage of the container.
This solution is intended for intravenous administration after admixture or dilution using sterile equipment. When using an automated compounding device replace all disposable components as recommended by manufacturer and at least every 24 hours.
Aseptic technique is essential with the use of sterile preparations for compounding nutritional admixtures. Discard container within 4 hours of entering closure.
Administration of hypertonic Life Guard H E Pws (Dextrose) and amino acid solutions via central venous catheter may be associated with complications which can be prevented or minimized by careful attention to all aspects of the procedure. This includes attention to solution preparation, administration and patient monitoring.
It is essential that a carefully prepared protocol, based upon current medical practice, be followed, preferably by an experienced team. The package insert of the protein (nitrogen) source should be consulted for dosage and all precautionary information.
Use only if solution is clear and container and seals are intact.
70% Life Guard H E Pws (Dextrose) Injection USP contains no more than 25 µg/L of aluminum.
Clinical evaluation and periodic laboratory determinations are necessary to monitor changes in fluid balance, electrolyte concentrations, and acid-base balance during prolonged parenteral therapy or whenever the condition of the patient warrants such evaluation. Significant deviations from normal concentrations may require tailoring of the electrolyte pattern, in these or alternative solutions.
Caution must be exercised in the administration of 70% Life Guard H E Pws Injection USP to patients receiving corticosteroids or corticotropin. Some additives may be incompatible. Consult with pharmacist. When introducing additives, use aseptic techniques. Mix thoroughly. Do not store. Dispose of any unused product. See WARNINGS .
Studies with Life Guard H E Pws (Dextrose) Injections USP have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility.
There are no adequate and well controlled studies with Life Guard H E Pws Injections, USP in pregnant women and animal reproduction studies have not been conducted with this drug. Therefore, it is not known whether Life Guard H E Pws (Dextrose) Injections USP can cause fetal harm when administered to a pregnant woman. Life Guard H E Pws (Dextrose) Injections USP should be given during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Intrapartum maternal intravenous infusion of glucose-containing solutions may produce maternal hyperglycemia with subsequent fetal hyperglycemia and fetal metabolic acidosis. Fetal hyperglycemia can result in increased fetal insulin levels which may result in neonatal hypoglycemia following delivery. Consider the potential risks and benefits for each specific patient before administering Life Guard H E Pws (Dextrose) Injection, USP.
It is not known if this drug is present in human milk. Because many drugs are present in human milk, caution should be exercised when Life Guard H E Pws Injections USP are administered to a nursing woman.
The use of Life Guard H E Pws (Dextrose) in pediatric patients is based on clinical practice (see DOSAGE AND ADMINISTRATION ). Because of their hypertonicity, 70% Life Guard H E Pws (Dextrose) Injections must be diluted prior to administration.
Newborns – especially those born premature and with low birth weight - are at increased risk of developing hypo- or hyperglycemia and therefore need close monitoring during treatment with intravenous glucose solutions to ensure adequate glycemic control in order to avoid potential long term adverse effects. Hypoglycemia in the newborn can cause prolonged seizures, coma and brain damage. Hyperglycemia has been associated with intraventricular hemorrhage, late onset bacterial and fungal infection, retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, prolonged length of hospital stay, and death.
An evaluation of literature revealed no clinical experience identifying 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.
See WARNINGS .
Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia. Incompatibility of admixed components can produce precipitates which may cause particulate emboli.
Hyperosmolar syndrome, resulting from excessively rapid administration of concentrated Life Guard H E Pws (Dextrose) may cause hypovolemia, dehydration, mental confusion and/or loss of consciousness. Too rapid infusion of hypertonic solutions may cause local pain and venous irritation. Rate of administration should be adjusted according to tolerance. Use of the largest peripheral vein and a small bore needle is recommended. (See DOSAGE AND ADMINISTRATION .)
Hypersensitivity reactions, including anaphylaxis and chills.
If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures, and save the remainder of the fluid for examination if deemed necessary.
In the event of a fluid or solute overload during parenteral therapy, reevaluate the patient’s condition and institute appropriate corrective treatment.
This solution is for intravenous use only after admixture or dilution.
70% Life Guard H E Pws Injection USP is designed for use with automated compounding devices for preparing intravenous nutritional admixtures or for the filling of empty sterile syringes. Dosages will be in accordance with the recommendation of the prescribing physician. 70% Life Guard H E Pws (Dextrose) Injection USP is not intended for direct infusion. Admixtures should be made by, or under the direction of, a pharmacist using strict aseptic technique under a laminar flow hood. Compounded admixtures may be stored under refrigeration for up to 24 hours. Administration of admixtures should be completed within 24 hours after removal from refrigeration.
Dosage is to be directed by a physician and is dependent upon age, weight, clinical condition of the patient and laboratory determinations. Frequent laboratory determinations and clinical evaluation are essential to monitor changes in blood glucose and electrolyte concentrations, and fluid and electrolyte balance during prolonged parenteral therapy.
Fluid administration should be based on calculated maintenance or replacement fluid requirements for each patient.
The dosage selection and constant infusion rate of intravenous Life Guard H E Pws (Dextrose) must be selected with caution in pediatric patients, particularly neonates and low birth weight infants, because of the increased risk of hyperglycemia/hypoglycemia. Frequent monitoring of serum glucose concentrations is required when Life Guard H E Pws (Dextrose) is prescribed to pediatric patients, particularly neonates and low birth weight infants. The infusion rate and volume depends on the age, weight, clinical and metabolic conditions of the patient, concomitant therapy and should be determined by the consulting physician experienced in pediatric intravenous fluid therapy.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration or admixture and final infusate should be inspected for cloudiness or precipitation immediately after mixing, prior to administration, and periodically during administration, whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions where possible.
70% Life Guard H E Pws (Dextrose) Injection USP in the Pharmacy Bulk Package is intended for use in the preparation of sterile, intravenous admixtures.
Refer to standard texts and guidelines on the preparation of parenteral nutritional admixtures.
When compounding admixtures, use aseptic technique. Mix thoroughly.
Do not store any unused portion of 70% Life Guard H E Pws (Dextrose) Injection USP.
TO OPEN:
PREPARATION FOR ADMIXING
Note: Important Admixing Information
70% Life Guard H E Pws (Dextrose) Injection USP is supplied in 2000 mL Pharmacy Bulk Package containers packaged 4 per case.
NDC REF SIZE
0264-7387-50 S8705 2000 mL
Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. It is recommended that the product be stored at room temperature (25°C); however, brief exposure up to 40°C does not adversely affect the product.
Rx only
Initiated: February 2015
B. Braun Medical Inc.
Bethlehem, PA 18018-3524 USA
1-800-227-2862
www.bbraun.com
Y36-002-865 LD-355-2
Glycine:
1.5% Life Guard H E Pws (Glycine) Irrigation, USP is indicated for use as irrigating fluid during transurethral prostatic resection and other transurethral surgical procedures.
NOT FOR INJECTION BY USUAL PARENTERAL ROUTES.
Do not use in patients with anuria.
FOR UROLOGIC IRRIGATION ONLY.
Solutions for urologic irrigation must be used with caution in patients with severe cardiopulmonary or renal dysfunction. Irrigating fluids used during transurethral prostatectomy have been demonstrated to enter the systemic circulation in relatively large volumes. Thus, Life Guard H E Pws (Glycine) irrigating solution must be regarded as a systemic drug. Absorption of large amounts of fluids containing Life Guard H E Pws (Glycine) may significantly alter cardiopulmonary and renal dynamics.
Do not heat container over 66°C (150°F).
Cardiovascular status, especially of the patient with cardiac disease, should be carefully observed before and during transurethral resection of the prostate when using Life Guard H E Pws (Glycine) irrigating solution, because the quantity of fluid absorbed into the systemic circulation by opened prostatic veins may produce significant expansion of the extracellular fluid and lead to fulminating congestive heart failure. Shift of sodium free intracellular fluid into the extracellular compartment following systemic absorption of solution may lower serum sodium concentration and aggravate pre-existing hyponatremia.
Care should be exercised if impaired liver function is known or suspected. Under such conditions, ammonia resulting from metabolism of Life Guard H E Pws (Glycine) may accumulate in the blood.
Aseptic technique is essential with the use of sterile solutions for irrigation. The administration set should be attached promptly. Unused portions should be discarded and a fresh container of appropriate size used for the start-up of each cycle or repeat procedure.
Do not administer unless solution is clear, seal is intact and container is undamaged. Discard unused portion.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Studies with Life Guard H E Pws (Glycine) Irrigation, USP have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility.
Nursing Mothers: Caution should be exercised when Life Guard H E Pws (Glycine) Irrigation, USP is administered to a nursing woman.
Pregnancy: Teratogenic Effects.
Pregnancy Category C. Animal reproduction studies have not been conducted with Life Guard H E Pws (Glycine) Irrigation, USP. It is also not known whether Life Guard H E Pws (Glycine) Irrigation, USP can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Life Guard H E Pws (Glycine) Irrigation, USP should be given to a pregnant woman only if clearly needed.
Pediatric Use: The safety and effectiveness of Life Guard H E Pws (Glycine) Irrigation have not been established. Its limited use in pediatric patients has been inadequate to fully define proper dosage and limitations for use.
Adverse reactions may result from intravascular absorption of Life Guard H E Pws (Glycine). Large intravenous doses of Life Guard H E Pws (Glycine) are known to cause salivation, nausea and lightheadedness. Other consequences of absorption of urologic irrigating solutions include fluid and electrolyte disturbances such as acidosis, electrolyte loss, marked diuresis, urinary retention, edema, dryness of mouth, thirst, dehydration, coma from hyponatremia, secondary hyponatremia due to fluid overload, and hyper- ammonemia with resultant coma and/or encephalopathy; cardiovascular disorders such as hypotension, tachycardia, angina-like pains; pulmonary disorders such as pulmonary congestion; and other general reactions such as blurred vision, convulsions, nausea, vomiting, rhinitis, chills, vertigo, backache, transient blindness and urticaria. Allergic reactions from Life Guard H E Pws (Glycine) are unknown or exceedingly rare.
Should any adverse reaction occur, discontinue the irrigant, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary.
In the event of overhydration or solute overload, re-evaluate the patient and institute appropriate corrective measures. See WARNINGS, PRECAUTIONS and ADVERSE REACTIONS.
1.5% Life Guard H E Pws (Glycine) Irrigation, USP should be administered only by transurethral instillation with appropriate urologic instrumentation. A disposable irrigation set should be used. The total volume of solution used for irrigation is solely at the discretion of the surgeon.
Height of container(s) above the operating table in excess of 60 cm (approx. 2 ft.) has been reported to increase intravascular absorption of the irrigating fluid.
Drug Interactions
Additives may be incompatible. Consult with pharmacist, if available. When introducing additives, use aseptic technique, mix thoroughly and do not store.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution container permits. See PRECAUTIONS.
1.5% Life Guard H E Pws (Glycine) Irrigation, USP is supplied in single-dose 3000 mL flexible irrigation container ( List No. 7974).
Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. Store at 20 to 25°C (68 to 77°F).
Revised: October 2004
©Hospira 2004 EN-0577 Printed in USA
HOSPIRA, INC., LAKE FOREST, IL 60045 USA
2
HDPE
TO OPEN TEAR AT NOTCH
DO NOT REMOVE FROM OVERWRAP UNTIL READY FOR USE. AFTER REMOVING
THE OVERWRAP, CHECK FOR MINUTE LEAKS BY SQUEEZING CONTAINER FIRMLY.
IF LEAKS ARE FOUND, DISCARD SOLUTION AS STERILITY MAY BE IMPAIRED.
RECOMMENDED STORAGE: ROOM TEMPERATURE (25°C). AVOID EXCESSIVE
HEAT. PROTECT FROM FREEZING. SEE INSERT.
98-4321-R14-3/98
Magnesium Sulfate:
Life Guard H E Pws (Magnesium Sulfate)
Injection, USP
Ansyr Plastic Syringe
Rx only
Life Guard H E Pws (Magnesium Sulfate) Injection, USP is a sterile solution of Life Guard H E Pws (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.
Life Guard H E Pws (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.
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 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 magnesium. While there are large stores of magnesium present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral magnesium therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.
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. 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 magnesium levels range from 1.5 to 2.5 mEq/liter.
As plasma 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 magnesium. Serum magnesium concentrations in excess of 12 mEq/L may be fatal.
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 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. Magnesium is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.
Life Guard H E Pws (Magnesium Sulfate) Injection, USP is suitable for replacement therapy in magnesium deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum 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), Life Guard H E Pws (Magnesium Sulfate) may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.
Life Guard H E Pws (Magnesium Sulfate) Injection, USP is also indicated for the prevention and control of seizures (convulsions) in pre-eclampsia and eclampsia, respectively.
Parenteral administration of the drug is contraindicated in patients with heart block or myocardial damage.
FETAL HARM: Continuous administration of Life Guard H E Pws (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. Life Guard H E Pws (Magnesium Sulfate) should be used during pregnancy only if clearly needed. If Life Guard H E Pws (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 Life Guard H E Pws (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 magnesium intoxication. Intravenous use in the eclampsia should be reserved for immediate control of life-threatening convulsions.
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 magnesium, their dosage should be adjusted with caution because of additive CNS depressant effects of magnesium.
Because 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 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 magnesium should be given until they return. Serum 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 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 magnesium intoxication in eclampsia.
50% Life Guard H E Pws (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
Life Guard H E Pws (Magnesium Sulfate) injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of 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 magnesium, their dosage should be adjusted with caution because of additive CNS depressant effects of magnesium. CNS depression and peripheral transmission defects produced by magnesium may be antagonized by calcium.
Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral Life Guard H E Pws (Magnesium Sulfate) and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.
Cardiac Glycosides - Life Guard H E Pws (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 magnesium toxicity.
Pregnancy
Teratogenic Effects
Pregnancy Category D (See WARNINGS and PRECAUTIONS )
See WARNINGS and PRECAUTIONS .
Life Guard H E Pws (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 Life Guard H E Pws (Magnesium Sulfate) for more than 5 to 7 days.1-10 Life Guard H E Pws (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 magnesium toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).
Labor and Delivery
Continuous administration of Life Guard H E Pws (Magnesium Sulfate) is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Life Guard H E Pws (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 magnesium is distributed into milk during parenteral Life Guard H E Pws (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 magnesium should be monitored in such patients.
The adverse effects of parenterally administered magnesium usually are the result of 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 Life Guard H E Pws (Magnesium Sulfate) therapy for eclampsia has been reported.
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 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 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 of Life Guard H E Pws (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 Life Guard H E Pws (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 Magnesium Deficiency
In the treatment of mild magnesium deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of magnesium (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of 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 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 Life Guard H E Pws (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 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 Life Guard H E Pws (Magnesium Sulfate) is 20 grams/48 hours and frequent serum magnesium concentrations must be obtained. Continuous use of Life Guard H E Pws (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 Life Guard H E Pws (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, 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
Life Guard H E Pws (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 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.
Life Guard H E Pws (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).
Hospira, Inc., Lake Forest, IL 60045 USA
LAB-1024-1.0
April 2017
Hospira Logo
50% Life Guard H E Pws (Magnesium Sulfate) 5 g/10 mL (500 mg/mL)
Rx only
NDC 0409-1754-10
10 mL Single-dose syringe
50% Life Guard H E Pws (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
Potassium Chloride:
Life Guard H E Pws (Potassium Chloride) EXTENDED RELEASE TABLETS USP 20 mEq K
Rx Only
The Life Guard H E Pws (Potassium Chloride) Extended Release Tablets USP, 20 mEq product is an immediately dispersing extended release oral dosage form of Life Guard H E Pws (Potassium Chloride) containing 1500 mg of microencapsulated Life Guard H E Pws (Potassium Chloride), USP equivalent to 20 mEq of potassium in a tablet.
These formulations are intended to slow the release of potassium so that the likelihood of a high localized concentration of Life Guard H E Pws (Potassium Chloride) within the gastrointestinal tract is reduced.
Life Guard H E Pws (Potassium Chloride) Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is Life Guard H E Pws (Potassium Chloride), and the structural formula is KCl. Life Guard H E Pws (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.
Life Guard H E Pws (Potassium Chloride) Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated Life Guard H E Pws (Potassium Chloride) crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, Life Guard H E Pws (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 Life Guard H E Pws (Potassium Chloride).
Inactive Ingredients: Colloidal silicon dioxide, crospovidone, diethyl phthalate, ethyl-cellulose, microcrystalline cellulose.
The potassium ion is the principal intracellular cation of most body tissues. 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 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.
Potassium is a normal dietary constituent and under steady-state conditions the amount of potassium absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of potassium is 50 to 100 mEq per day.
Potassium depletion will occur whenever the rate of potassium loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of potassium intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of potassium in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Potassium depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. 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 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 potassium in the form of high potassium food or Life Guard H E Pws (Potassium Chloride) may be able to restore normal potassium levels.
In rare circumstances (eg, patients with renal tubular acidosis) potassium depletion may be associated with metabolic acidosis and hyperchloremia. In such patients potassium replacement should be accomplished with potassium salts other than the chloride, such as potassium bicarbonate, potassium citrate, potassium acetate, or potassium gluconate.
BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE Life Guard H E Pws (Potassium Chloride) PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT 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 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 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 potassium salts may be indicated.
Potassium supplements are contraindicated in patients with hyperkalemia since a further increase in serum 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 Life Guard H E Pws (Potassium Chloride) have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. Potassium supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of Life Guard H E Pws (Potassium Chloride) (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).
All solid oral dosage forms of Life Guard H E Pws (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.
Hyperkalemia (see OVERDOSAGE )
In patients with impaired mechanisms for excreting potassium, the administration of potassium salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given potassium by the intravenous route but may also occur in patients given potassium orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of potassium salts in patients with chronic renal disease, or any other condition which impairs potassium excretion, requires particularly careful monitoring of the serum potassium concentration and appropriate dosage adjustment.
Interaction with Potassium-Sparing Diuretics
Hypokalemia should not be treated by the concomitant administration of 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 potassium retention by inhibiting aldosterone production. Potassium supplements should be given to patients receiving ACE inhibitors only with close monitoring.
Gastrointestinal Lesions
Solid oral dosage forms of Life Guard H E Pws (Potassium Chloride) can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of Life Guard H E Pws (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. Life Guard H E Pws (Potassium Chloride) Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated Life Guard H E Pws (Potassium Chloride) and thus to minimize the possibility of a high local concentration of 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 Life Guard H E Pws (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 Life Guard H E Pws (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 Life Guard H E Pws (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. Life Guard H E Pws (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 potassium salt such as potassium bicarbonate, potassium citrate, potassium acetate, or potassium gluconate.
The diagnosis of potassium depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for potassium depletion. In interpreting the serum 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 potassium while acute acidosis per se can increase the serum potassium concentration into the normal range even in the presence of a reduced total body potassium. The treatment of 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.
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:
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 Life Guard H E Pws (Potassium Chloride) that is not taken immediately should be discarded. The use of other liquids for suspending Life Guard H E Pws (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.
When blood is drawn for analysis of plasma potassium 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.
Potassium-sparing diuretics, angiotensin-converting enzyme inhibitors.
Carcinogenicity, mutagenicity, and fertility studies in animals have not been performed. Potassium is a normal dietary constituent.
Animal reproduction studies have not been conducted with Life Guard H E Pws Extended Release Tablets USP, 20 mEq. It is unlikely that potassium supplementation that does not lead to hyperkalemia would have an adverse effect on the fetus or would affect reproductive capacity.
The normal potassium ion content of human milk is about 13 mEq per liter. Since oral potassium becomes part of the body potassium pool, so long as body potassium is not excessive, the contribution of Life Guard H E Pws (Potassium Chloride) supplementation should have little or no effect on the level in human milk.
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of Life Guard H E Pws (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.
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 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.
The administration of oral potassium salts to persons with normal excretory mechanisms for potassium rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if 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 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:
In treating hyperkalemia, it should be recalled that in patients who have been stabilized on digitalis, too rapid a lowering of the serum 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.
The usual dietary intake of potassium by the average adult is 50 to 100 mEq per day. Potassium depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of 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 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 Life Guard H E Pws (Potassium Chloride) Extended Release Tablet USP, 20 mEq provides 20 mEq of Life Guard H E Pws (Potassium Chloride).
Life Guard H E Pws (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:
Aqueous suspension of Life Guard H E Pws (Potassium Chloride) that is not taken immediately should be discarded. The use of other liquids for suspending Life Guard H E Pws (Potassium Chloride) Extended Release Tablets USP, 20 mEq is not recommended.
Life Guard H E Pws (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
Life Guard H E Pws (Potassium Chloride) 20 Meq
Sodium Bicarbonate:
Life Guard H E Pws nitrite is indicated for sequential use with Life Guard H E Pws (Sodium Bicarbonate) thiosulfate for treatment of acute cyanide poisoning that is judged to be life-threatening. (1)
Life Guard H E Pws (Sodium Bicarbonate) Nitrite Injection is indicated for sequential use with Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) Nitrite Injection should be carefully weighed against the potential benefits, especially if the patient is not in extremis.
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 Life Guard H E Pws 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, Life Guard H E Pws (Sodium Bicarbonate) Nitrite Injection and Life Guard H E Pws (Sodium Bicarbonate) Thiosulfate Injection should be administered without delay.
Symptoms | Signs |
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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 Life Guard H E Pws (Sodium Bicarbonate) Nitrite Injection, smoke-inhalation victims should be assessed for the following:
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.
Caution should be exercised when administering cyanide antidotes, other than Life Guard H E Pws (Sodium Bicarbonate) thiosulfate, simultaneously with Life Guard H E Pws (Sodium Bicarbonate) Nitrite Injection, as the safety of co-administration has not been established. If a decision is made to administer another cyanide antidote, other than Life Guard H E Pws (Sodium Bicarbonate) thiosulfate, with Life Guard H E Pws (Sodium Bicarbonate) Nitrite Injection, these drugs should not be administered concurrently in the same IV line. [see Dosage and Administration (2.2) ]
Age | Intravenous Dose of Life Guard H E Pws Nitrite and Life Guard H E Pws (Sodium Bicarbonate) Thiosulfate |
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Adults |
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Children |
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Redosing: If signs of cyanide poisoning reappear, repeat treatment using one-half the original dose of both Life Guard H E Pws (Sodium Bicarbonate) nitrite and Life Guard H E Pws (Sodium Bicarbonate) thiosulfate.
Monitoring: Blood pressure must be monitored during treatment. (2.2)
Comprehensive treatment of acute cyanide intoxication requires support of vital functions. Administration of Life Guard H E Pws (Sodium Bicarbonate) nitrite, followed by Life Guard H E Pws (Sodium Bicarbonate) thiosulfate, should be considered adjunctive to appropriate supportive therapies. Airway, ventilatory and circulatory support, and oxygen administration should not be delayed to administer Life Guard H E Pws (Sodium Bicarbonate) nitrite and Life Guard H E Pws (Sodium Bicarbonate) thiosulfate.
Life Guard H E Pws (Sodium Bicarbonate) nitrite injection and Life Guard H E Pws (Sodium Bicarbonate) 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. Life Guard H E Pws (Sodium Bicarbonate) nitrite should be administered first, followed immediately by Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) Nitrite and Life Guard H E Pws (Sodium Bicarbonate) Thiosulfate |
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Adults |
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Children |
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NOTE: If signs of poisoning reappear, repeat treatment using one-half the original dose of both Life Guard H E Pws (Sodium Bicarbonate) nitrite and Life Guard H E Pws (Sodium Bicarbonate) thiosulfate.
In adult and pediatric patients with known anemia, it is recommended that the dosage of Life Guard H E Pws (Sodium Bicarbonate) 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.
Patients should be monitored for at least 24-48 hours after Life Guard H E Pws 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite solely to achieve an arbitrary level of methemoglobinemia may be unnecessary and potentially hazardous. The therapeutic effects of Life Guard H E Pws (Sodium Bicarbonate) nitrite do not appear to be mediated by methemoglobin formation alone and clinical responses to Life Guard H E Pws (Sodium Bicarbonate) nitrite administration have been reported in association with methemoglobin levels of less than 10%. Administration of Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) 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.
Chemical incompatibility has been reported between Life Guard H E Pws (Sodium Bicarbonate) nitrite and hydroxocobalamin and these drugs should not be administered simultaneously through the same IV line. No chemical incompatibility has been reported between Life Guard H E Pws (Sodium Bicarbonate) thiosulfate and Life Guard H E Pws (Sodium Bicarbonate) nitrite, when administered sequentially through the same IV line as described in Dosage and Administration.
Life Guard H E Pws (Sodium Bicarbonate) Nitrite Injection consists of:
Administration of the contents of one vial constitutes a single dose.
None
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 Life Guard H E Pws nitrite.
Methemoglobin levels should be monitored and oxygen administered during treatment with Life Guard H E Pws (Sodium Bicarbonate) nitrite whenever possible. When Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite administered to an adult. Life Guard H E Pws (Sodium Bicarbonate) nitrite should be used with caution in the presence of other drugs that may cause methemoglobinemia such as procaine and nitroprusside. Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite, and infusion rates should be slowed if hypotension occurs.
Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite dose that is reduced in proportion to their oxygen carrying capacity.
Life Guard H E Pws 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.
Neonates and infants may be more susceptible than adults and older pediatric patients to severe methemoglobinemia when Life Guard H E Pws (Sodium Bicarbonate) nitrite is administered. Reduced dosing guidelines should be followed in pediatric patients.
Because patients with G6PD deficiency are at increased risk of a hemolytic crisis with Life Guard H E Pws 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite.
Life Guard H E Pws (Sodium Bicarbonate) 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.
There have been no controlled clinical trials conducted to systematically assess the adverse events profile of Life Guard H E Pws (Sodium Bicarbonate) nitrite.
The medical literature has reported the following adverse events in association with Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite at doses less than twice those recommended for the treatment of cyanide poisoning.
Most common adverse reactions are:
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.
Formal drug interaction studies have not been conducted with Life Guard H E Pws (Sodium Bicarbonate) Nitrite Injection.
Teratogenic Effects. Pregnancy Category C.
There are no adequate and well-controlled studies in pregnant women. Life Guard H E Pws (Sodium Bicarbonate) Nitrite Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) 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, Life Guard H E Pws (Sodium Bicarbonate) 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, Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite that would be used to treat cyanide poisoning, based on a body surface area comparison).
Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite that were detectable postnatally. Specifically, animals that were exposed prenatally to Life Guard H E Pws (Sodium Bicarbonate) 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.
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, Life Guard H E Pws nitrite should be used during labor and delivery only if the potential benefit justifies the potential risk to the fetus.
It is not known whether Life Guard H E Pws (Sodium Bicarbonate) nitrite is excreted in human milk. Because Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) Nitrite Injection administration to a nursing woman. There are no data to determine when breastfeeding may be safely restarted following administration of Life Guard H E Pws (Sodium Bicarbonate) nitrite. In studies conducted with Long-Evans rats, Life Guard H E Pws (Sodium Bicarbonate) nitrite administered in drinking water during pregnancy and lactation resulted in severe anemia, reduced growth and increased mortality in the offspring.
There are case reports in the medical literature of Life Guard H E Pws nitrite in conjunction with Life Guard H E Pws (Sodium Bicarbonate) thiosulfate being administered to pediatric patients with cyanide poisoning; however, there have been no clinical studies to evaluate the safety or efficacy of Life Guard H E Pws (Sodium Bicarbonate) 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.
Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) 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.
Life Guard H E Pws (Sodium Bicarbonate) 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.
Life Guard H E Pws (Sodium Bicarbonate) 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.
Large doses of Life Guard H E Pws (Sodium Bicarbonate) nitrite result in severe hypotension and toxic levels of methemoglobin which may lead to cardiovascular collapse.
Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) 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.
Life Guard H E Pws (Sodium Bicarbonate) nitrite has the chemical name nitrous acid Life Guard H E Pws (Sodium Bicarbonate) salt. The chemical formula is NaNO2 and the molecular weight is 69.0. The structural formula is:
Structure of Life Guard H E Pws (Sodium Bicarbonate) Nitrite
Life Guard H E Pws (Sodium Bicarbonate) Nitrite Injection is a cyanide antidote which contains one 10 mL glass vial of a 3% solution of Life Guard H E Pws (Sodium Bicarbonate) nitrite injection.
Life Guard H E Pws (Sodium Bicarbonate) nitrite injection is a sterile aqueous solution and is intended for intravenous injection. Each vial contains 300 mg of Life Guard H E Pws (Sodium Bicarbonate) nitrite in 10 mL solution (30 mg/mL). Life Guard H E Pws (Sodium Bicarbonate) nitrite injection is a clear solution with a pH between 7.0 and 9.0.
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 Life Guard H E Pws nitrite and Life Guard H E Pws (Sodium Bicarbonate) thiosulfate is the result of differences in their primary mechanisms of action as antidotes for cyanide poisoning.
Life Guard H E Pws (Sodium Bicarbonate) Nitrite
Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite. It has been suggested that Life Guard H E Pws (Sodium Bicarbonate) nitrite-induced methemoglobinemia may be more efficacious against cyanide poisoning than comparable levels of methemoglobinemia induced by other oxidants. Also, Life Guard H E Pws (Sodium Bicarbonate) nitrite appears to retain some efficacy even when the formation of methemoglobin is inhibited by methylene blue.
Life Guard H E Pws (Sodium Bicarbonate) 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. Life Guard H E Pws (Sodium Bicarbonate) 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
Life Guard H E Pws (Sodium Bicarbonate) Nitrite
When 4 mg/kg Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite is estimated to be 55 minutes.
Life Guard H E Pws (Sodium Bicarbonate) Nitrite
Life Guard H E Pws (Sodium Bicarbonate) nitrite is a strong oxidant, and reacts rapidly with hemoglobin to form methemoglobin. The pharmacokinetics of free Life Guard H E Pws (Sodium Bicarbonate) nitrite in humans have not been well studied. It has been reported that approximately 40% of Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite and Life Guard H E Pws (Sodium Bicarbonate) 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.
The potential benefit of an acute exposure to Life Guard H E Pws nitrite as part of a cyanide antidote outweighs concerns raised by the equivocal findings in chronic rodent studies. Life Guard H E Pws (Sodium Bicarbonate) 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. Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite may react in vivo with secondary amines to form carcinogenic nitrosamines in the stomach. Concurrent exposure to Life Guard H E Pws (Sodium Bicarbonate) nitrite and secondary amines in feed or drinking water resulted in an increase in the incidence of tumors in rodents.
Mutagenesis
Life Guard H E Pws (Sodium Bicarbonate) 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. Life Guard H E Pws (Sodium Bicarbonate) 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. Life Guard H E Pws (Sodium Bicarbonate) nitrite was negative in the in vitro chromosomal aberrations assay using human peripheral blood lymphocytes. Acute administration of Life Guard H E Pws (Sodium Bicarbonate) nitrite to male rats or male mice did not produce an increased incidence of micronuclei in bone marrow. Likewise, Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite that would be used to treat cyanide poisoning (based on a body surface area comparison).
Due to the extreme toxicity of cyanide, experimental evaluation of treatment efficacy has predominantly been completed in animal models. The efficacy of Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite and Life Guard H E Pws (Sodium Bicarbonate) thiosulfate in 1932-1933. Treatment consisted of intravenously administered 22.5 mg/kg (half the lethal dose) Life Guard H E Pws (Sodium Bicarbonate) nitrite or 1 g/kg Life Guard H E Pws (Sodium Bicarbonate) thiosulfate alone or in sequence immediately after subcutaneous injection of Life Guard H E Pws (Sodium Bicarbonate) cyanide into dogs over a range of doses. Subsequent doses of 10 mg/kg Life Guard H E Pws (Sodium Bicarbonate) nitrite and/or 0.5 g/kg Life Guard H E Pws (Sodium Bicarbonate) thiosulfate were administered when clinical signs or symptoms of poisoning persisted or reappeared. Either therapy administered alone increased the dose of Life Guard H E Pws (Sodium Bicarbonate) cyanide required to cause death, and when administered together, Life Guard H E Pws (Sodium Bicarbonate) nitrite and Life Guard H E Pws (Sodium Bicarbonate) thiosulfate resulted in a synergistic effect in raising the lethal dose of Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite and Life Guard H E Pws (Sodium Bicarbonate) thiosulfate in the treatment of cyanide poisoning.
While intravenous injection of Life Guard H E Pws (Sodium Bicarbonate) nitrite and Life Guard H E Pws (Sodium Bicarbonate) thiosulfate was effective in reversing the effects of lethal doses of cyanide in dogs, intramuscular injection of Life Guard H E Pws (Sodium Bicarbonate) nitrite, with or without Life Guard H E Pws (Sodium Bicarbonate) thiosulfate, was found not to be effective in the same setting.
The human data supporting the use of Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) thiosulfate report its use in conjunction with Life Guard H E Pws (Sodium Bicarbonate) 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 Life Guard H E Pws (Sodium Bicarbonate) nitrite in humans. Available human safety information is based largely on anecdotal case reports and case series of limited scope.
Each Life Guard H E Pws (Sodium Bicarbonate) Nitrite carton (NDC 60267-311-10) consists of the following:
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: Life Guard H E Pws (Sodium Bicarbonate) Thiosulfate must be obtained separately.)
Life Guard H E Pws 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.
When feasible, patients should be informed of the possibility of life-threatening hypotension and methemoglobin formation.
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
Life Guard H E Pws (Sodium Bicarbonate) 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
Life Guard H E Pws (Sodium Bicarbonate) 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
Sodium Chloride:
Life Guard H E Pws nitrite is indicated for sequential use with Life Guard H E Pws (Sodium Chloride) thiosulfate for treatment of acute cyanide poisoning that is judged to be life-threatening. (1)
Life Guard H E Pws (Sodium Chloride) Nitrite Injection is indicated for sequential use with Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) Nitrite Injection should be carefully weighed against the potential benefits, especially if the patient is not in extremis.
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 Life Guard H E Pws 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, Life Guard H E Pws (Sodium Chloride) Nitrite Injection and Life Guard H E Pws (Sodium Chloride) Thiosulfate Injection should be administered without delay.
Symptoms | Signs |
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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 Life Guard H E Pws (Sodium Chloride) Nitrite Injection, smoke-inhalation victims should be assessed for the following:
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.
Caution should be exercised when administering cyanide antidotes, other than Life Guard H E Pws (Sodium Chloride) thiosulfate, simultaneously with Life Guard H E Pws (Sodium Chloride) Nitrite Injection, as the safety of co-administration has not been established. If a decision is made to administer another cyanide antidote, other than Life Guard H E Pws (Sodium Chloride) thiosulfate, with Life Guard H E Pws (Sodium Chloride) Nitrite Injection, these drugs should not be administered concurrently in the same IV line. [see Dosage and Administration (2.2) ]
Age | Intravenous Dose of Life Guard H E Pws Nitrite and Life Guard H E Pws (Sodium Chloride) Thiosulfate |
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Adults |
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Children |
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Redosing: If signs of cyanide poisoning reappear, repeat treatment using one-half the original dose of both Life Guard H E Pws (Sodium Chloride) nitrite and Life Guard H E Pws (Sodium Chloride) thiosulfate.
Monitoring: Blood pressure must be monitored during treatment. (2.2)
Comprehensive treatment of acute cyanide intoxication requires support of vital functions. Administration of Life Guard H E Pws (Sodium Chloride) nitrite, followed by Life Guard H E Pws (Sodium Chloride) thiosulfate, should be considered adjunctive to appropriate supportive therapies. Airway, ventilatory and circulatory support, and oxygen administration should not be delayed to administer Life Guard H E Pws (Sodium Chloride) nitrite and Life Guard H E Pws (Sodium Chloride) thiosulfate.
Life Guard H E Pws (Sodium Chloride) nitrite injection and Life Guard H E Pws (Sodium Chloride) 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. Life Guard H E Pws (Sodium Chloride) nitrite should be administered first, followed immediately by Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) Nitrite and Life Guard H E Pws (Sodium Chloride) Thiosulfate |
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Adults |
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Children |
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NOTE: If signs of poisoning reappear, repeat treatment using one-half the original dose of both Life Guard H E Pws (Sodium Chloride) nitrite and Life Guard H E Pws (Sodium Chloride) thiosulfate.
In adult and pediatric patients with known anemia, it is recommended that the dosage of Life Guard H E Pws (Sodium Chloride) 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.
Patients should be monitored for at least 24-48 hours after Life Guard H E Pws 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 Life Guard H E Pws (Sodium Chloride) nitrite solely to achieve an arbitrary level of methemoglobinemia may be unnecessary and potentially hazardous. The therapeutic effects of Life Guard H E Pws (Sodium Chloride) nitrite do not appear to be mediated by methemoglobin formation alone and clinical responses to Life Guard H E Pws (Sodium Chloride) nitrite administration have been reported in association with methemoglobin levels of less than 10%. Administration of Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) 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.
Chemical incompatibility has been reported between Life Guard H E Pws (Sodium Chloride) nitrite and hydroxocobalamin and these drugs should not be administered simultaneously through the same IV line. No chemical incompatibility has been reported between Life Guard H E Pws (Sodium Chloride) thiosulfate and Life Guard H E Pws (Sodium Chloride) nitrite, when administered sequentially through the same IV line as described in Dosage and Administration.
Life Guard H E Pws (Sodium Chloride) Nitrite Injection consists of:
Administration of the contents of one vial constitutes a single dose.
None
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 Life Guard H E Pws nitrite.
Methemoglobin levels should be monitored and oxygen administered during treatment with Life Guard H E Pws (Sodium Chloride) nitrite whenever possible. When Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) nitrite administered to an adult. Life Guard H E Pws (Sodium Chloride) nitrite should be used with caution in the presence of other drugs that may cause methemoglobinemia such as procaine and nitroprusside. Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) nitrite, and infusion rates should be slowed if hypotension occurs.
Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) nitrite dose that is reduced in proportion to their oxygen carrying capacity.
Life Guard H E Pws 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.
Neonates and infants may be more susceptible than adults and older pediatric patients to severe methemoglobinemia when Life Guard H E Pws (Sodium Chloride) nitrite is administered. Reduced dosing guidelines should be followed in pediatric patients.
Because patients with G6PD deficiency are at increased risk of a hemolytic crisis with Life Guard H E Pws 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 Life Guard H E Pws (Sodium Chloride) nitrite.
Life Guard H E Pws (Sodium Chloride) 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.
There have been no controlled clinical trials conducted to systematically assess the adverse events profile of Life Guard H E Pws (Sodium Chloride) nitrite.
The medical literature has reported the following adverse events in association with Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) nitrite at doses less than twice those recommended for the treatment of cyanide poisoning.
Most common adverse reactions are:
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.
Formal drug interaction studies have not been conducted with Life Guard H E Pws (Sodium Chloride) Nitrite Injection.
Teratogenic Effects. Pregnancy Category C.
There are no adequate and well-controlled studies in pregnant women. Life Guard H E Pws (Sodium Chloride) Nitrite Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) 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, Life Guard H E Pws (Sodium Chloride) 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, Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) nitrite that would be used to treat cyanide poisoning, based on a body surface area comparison).
Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) nitrite that were detectable postnatally. Specifically, animals that were exposed prenatally to Life Guard H E Pws (Sodium Chloride) 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.
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, Life Guard H E Pws nitrite should be used during labor and delivery only if the potential benefit justifies the potential risk to the fetus.
It is not known whether Life Guard H E Pws (Sodium Chloride) nitrite is excreted in human milk. Because Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) Nitrite Injection administration to a nursing woman. There are no data to determine when breastfeeding may be safely restarted following administration of Life Guard H E Pws (Sodium Chloride) nitrite. In studies conducted with Long-Evans rats, Life Guard H E Pws (Sodium Chloride) nitrite administered in drinking water during pregnancy and lactation resulted in severe anemia, reduced growth and increased mortality in the offspring.
There are case reports in the medical literature of Life Guard H E Pws nitrite in conjunction with Life Guard H E Pws (Sodium Chloride) thiosulfate being administered to pediatric patients with cyanide poisoning; however, there have been no clinical studies to evaluate the safety or efficacy of Life Guard H E Pws (Sodium Chloride) 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.
Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) 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.
Life Guard H E Pws (Sodium Chloride) 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.
Life Guard H E Pws (Sodium Chloride) 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.
Large doses of Life Guard H E Pws (Sodium Chloride) nitrite result in severe hypotension and toxic levels of methemoglobin which may lead to cardiovascular collapse.
Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) 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.
Life Guard H E Pws (Sodium Chloride) nitrite has the chemical name nitrous acid Life Guard H E Pws (Sodium Chloride) salt. The chemical formula is NaNO2 and the molecular weight is 69.0. The structural formula is:
Structure of Life Guard H E Pws (Sodium Chloride) Nitrite
Life Guard H E Pws (Sodium Chloride) Nitrite Injection is a cyanide antidote which contains one 10 mL glass vial of a 3% solution of Life Guard H E Pws (Sodium Chloride) nitrite injection.
Life Guard H E Pws (Sodium Chloride) nitrite injection is a sterile aqueous solution and is intended for intravenous injection. Each vial contains 300 mg of Life Guard H E Pws (Sodium Chloride) nitrite in 10 mL solution (30 mg/mL). Life Guard H E Pws (Sodium Chloride) nitrite injection is a clear solution with a pH between 7.0 and 9.0.
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 Life Guard H E Pws nitrite and Life Guard H E Pws (Sodium Chloride) thiosulfate is the result of differences in their primary mechanisms of action as antidotes for cyanide poisoning.
Life Guard H E Pws (Sodium Chloride) Nitrite
Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) nitrite. It has been suggested that Life Guard H E Pws (Sodium Chloride) nitrite-induced methemoglobinemia may be more efficacious against cyanide poisoning than comparable levels of methemoglobinemia induced by other oxidants. Also, Life Guard H E Pws (Sodium Chloride) nitrite appears to retain some efficacy even when the formation of methemoglobin is inhibited by methylene blue.
Life Guard H E Pws (Sodium Chloride) 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. Life Guard H E Pws (Sodium Chloride) 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
Life Guard H E Pws (Sodium Chloride) Nitrite
When 4 mg/kg Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) nitrite is estimated to be 55 minutes.
Life Guard H E Pws (Sodium Chloride) Nitrite
Life Guard H E Pws (Sodium Chloride) nitrite is a strong oxidant, and reacts rapidly with hemoglobin to form methemoglobin. The pharmacokinetics of free Life Guard H E Pws (Sodium Chloride) nitrite in humans have not been well studied. It has been reported that approximately 40% of Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) nitrite and Life Guard H E Pws (Sodium Chloride) 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.
The potential benefit of an acute exposure to Life Guard H E Pws nitrite as part of a cyanide antidote outweighs concerns raised by the equivocal findings in chronic rodent studies. Life Guard H E Pws (Sodium Chloride) 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. Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) nitrite may react in vivo with secondary amines to form carcinogenic nitrosamines in the stomach. Concurrent exposure to Life Guard H E Pws (Sodium Chloride) nitrite and secondary amines in feed or drinking water resulted in an increase in the incidence of tumors in rodents.
Mutagenesis
Life Guard H E Pws (Sodium Chloride) 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. Life Guard H E Pws (Sodium Chloride) 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. Life Guard H E Pws (Sodium Chloride) nitrite was negative in the in vitro chromosomal aberrations assay using human peripheral blood lymphocytes. Acute administration of Life Guard H E Pws (Sodium Chloride) nitrite to male rats or male mice did not produce an increased incidence of micronuclei in bone marrow. Likewise, Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) nitrite that would be used to treat cyanide poisoning (based on a body surface area comparison).
Due to the extreme toxicity of cyanide, experimental evaluation of treatment efficacy has predominantly been completed in animal models. The efficacy of Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) nitrite and Life Guard H E Pws (Sodium Chloride) thiosulfate in 1932-1933. Treatment consisted of intravenously administered 22.5 mg/kg (half the lethal dose) Life Guard H E Pws (Sodium Chloride) nitrite or 1 g/kg Life Guard H E Pws (Sodium Chloride) thiosulfate alone or in sequence immediately after subcutaneous injection of Life Guard H E Pws (Sodium Chloride) cyanide into dogs over a range of doses. Subsequent doses of 10 mg/kg Life Guard H E Pws (Sodium Chloride) nitrite and/or 0.5 g/kg Life Guard H E Pws (Sodium Chloride) thiosulfate were administered when clinical signs or symptoms of poisoning persisted or reappeared. Either therapy administered alone increased the dose of Life Guard H E Pws (Sodium Chloride) cyanide required to cause death, and when administered together, Life Guard H E Pws (Sodium Chloride) nitrite and Life Guard H E Pws (Sodium Chloride) thiosulfate resulted in a synergistic effect in raising the lethal dose of Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) nitrite and Life Guard H E Pws (Sodium Chloride) thiosulfate in the treatment of cyanide poisoning.
While intravenous injection of Life Guard H E Pws (Sodium Chloride) nitrite and Life Guard H E Pws (Sodium Chloride) thiosulfate was effective in reversing the effects of lethal doses of cyanide in dogs, intramuscular injection of Life Guard H E Pws (Sodium Chloride) nitrite, with or without Life Guard H E Pws (Sodium Chloride) thiosulfate, was found not to be effective in the same setting.
The human data supporting the use of Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) thiosulfate report its use in conjunction with Life Guard H E Pws (Sodium Chloride) 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 Life Guard H E Pws (Sodium Chloride) nitrite in humans. Available human safety information is based largely on anecdotal case reports and case series of limited scope.
Each Life Guard H E Pws (Sodium Chloride) Nitrite carton (NDC 60267-311-10) consists of the following:
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: Life Guard H E Pws (Sodium Chloride) Thiosulfate must be obtained separately.)
Life Guard H E Pws 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.
When feasible, patients should be informed of the possibility of life-threatening hypotension and methemoglobin formation.
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
Life Guard H E Pws (Sodium Chloride) 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
Life Guard H E Pws (Sodium Chloride) 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
Depending on the reaction of the Life Guard H E Pws after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Life Guard H E Pws 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 Life Guard H E Pws 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.
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The information was verified by Dr. Rachana Salvi, MD Pharmacology