Nephrotect

Acetylcysteine:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Use in specific populations
• Description
• Clinical pharmacology
• Nonclinical toxicology
• How supplied/storage and handling
• Patient counseling information
• Nephrotect (Acetylcysteine) reviews

1 INDICATIONS AND USAGE

Nephrotect (Acetylcysteine) is indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen in patients with acute ingestion or from repeated supratherapeutic ingestion (RSI).

Nephrotect (Acetylcysteine) is an antidote for acetaminophen overdose indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen in patients with acute ingestion or from repeated supratherapeutic ingestion. (1)

2 DOSAGE AND ADMINISTRATION

Pre-Treatment Assessment Following Acute Ingestion :

Obtain a plasma or serum sample to assay for acetaminophen concentration at least 4 hours after ingestion.

• If the time of acetaminophen ingestion is unknown:
  • Administer a loading dose of Nephrotect (Acetylcysteine) immediately.
  • Obtain an acetaminophen concentration to determine the need for continued treatment.
• If the acetaminophen concentration cannot be obtained (or is unavailable or uninterpretable) within the 8-hour time interval after acetaminophen ingestion or there is clinical evidence of acetaminophen toxicity:
  • Administer a loading dose of Nephrotect (Acetylcysteine) immediately and continue treatment for a total of 17 doses.
• If the patient presents more than 8 hours after ingestion and the time of acute acetaminophen ingestion is known:
  • Administer a loading dose of Nephrotect (Acetylcysteine) immediately.
  • Obtain acetaminophen concentration to determine need for continued treatment.
• If the patient presents less than 8 hours after ingestion and the time of acute acetaminophen ingestion is known and the acetaminophen concentration is known:
  • Use the Rumack-Matthew nomogram (Figure 1) to determine whether or not to initiate treatment with Nephrotect (Acetylcysteine). (2.2)

Nomogram for Estimating Potential for Hepatotoxicity from Acute Acetaminophen Ingestion (2.2):

• See the Full Prescribing Information for instructions on how to use the nomogram to determine the need for loading and maintenance dosing.

Recommended Adult and Pediatric Dosage (2.3):

• Nephrotect (Acetylcysteine) is for oral administration only; not for nebulization or intratracheal instillation.
• Loading dose: 140 mg/kg.
• Maintenance doses: 70 mg/kg repeated every 4 hours for a total of 17 doses.
• See Full Prescribing Information for weight-based dosage and preparation and administration instructions.

Repeated Supratherapeutic Acetaminophen Ingestion (2.4):

• Obtain acetaminophen concentration and other laboratory tests to guide treatment; Rumack-Matthew nomogram does not apply.

2.1 Pretreatment Assessment and Testing Following Acute Acetaminophen Ingestion

The following recommendations are related to acute acetaminophen ingestion. For recommendations related to repeated supratherapeutic exposure see Dosage and Administration (2.4) .

• Assess the history and timing of acetaminophen ingestion as an overdose.
  • The reported history of the quantity of acetaminophen ingested as an overdose is often inaccurate and is not a reliable guide to therapy.
• Obtain the following laboratory tests to monitor hepatic and renal function and electrolyte and fluid balance: aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, international normalized ratio (INR), creatinine, blood urea nitrogen (BUN), blood glucose, and electrolytes.
• Obtain a plasma or serum sample to assay for acetaminophen concentration at least 4 hours after ingestion. Acetaminophen concentrations obtained earlier than 4 hours post-ingestion may be misleading as they may not represent maximum acetaminophen concentrations.
• If the time of acute acetaminophen ingestion is unknown:
  • Administer a loading dose of Nephrotect (Acetylcysteine) immediately .
  • Obtain an acetaminophen concentration to determine need for continued treatment .
• If the acetaminophen concentration cannot be obtained (or is unavailable or uninterpretable) within the 8-hour time interval after acetaminophen ingestion or there is clinical evidence of acetaminophen toxicity:
  • Administer a loading dose of Nephrotect (Acetylcysteine) immediately and continue treatment for a total of 17 doses .
• If the patient presents more than 8 hours after ingestion and the time of acute acetaminophen ingestion is known:
  • Administer a loading dose of Nephrotect (Acetylcysteine) immediately .
  • Obtain acetaminophen concentration to determine need for continued treatment .
• If the patient presents less than 8 hours after ingestion and the time of acute acetaminophen ingestion is known and the acetaminophen concentration is known:
  • Use the Rumack-Matthew nomogram (Figure 1) to determine whether or not to initiate treatment with Nephrotect (Acetylcysteine) .

2.2 Nomogram for Estimating Potential for Hepatotoxicity from Acute Acetaminophen Ingestion and Need for Nephrotect Treatment

If the timing of the acute acetaminophen ingestion is known and the results of the acetaminophen assay are available within 8 hours:

• Refer to the Rumack-Matthew nomogram to determine whether or not to initiate treatment with Nephrotect (Acetylcysteine).
• Initiation of Nephrotect (Acetylcysteine) depends on the acetaminophen concentration and also the clinical presentation of the patient.

The nomogram may underestimate the hepatotoxicity risk in patients with chronic alcoholism, malnutrition, or CYP2E1 enzyme inducing drugs (e.g., isoniazid), and consideration should be given to treating these patients even if the acetaminophen concentrations are in the nontoxic range.

Loading Dose

For patients whose acetaminophen concentrations are at or above the "possible" toxicity line (dotted line in nomogram):

• Administer a loading dose of Nephrotect (Acetylcysteine) .

For patients with an acute overdose due to an extended-release acetaminophen, if the acetaminophen concentration at 4 hours post ingestion is below the possible toxicity line then obtain a second sample for acetaminophen concentration 8 to 10 hours after the acute ingestion. If the second value is at or above the "possible" toxicity line (dotted line in nomogram):

• Administer a loading dose of Nephrotect (Acetylcysteine) .

For patients whose values are below the "possible" toxicity line, but time of ingestion was unknown or sample was obtained less than 4 hours after ingestion:

• Administer a loading dose of Nephrotect (Acetylcysteine) .

For patients whose values are below the "possible" toxicity line and time of ingestion is known and the sample was obtained more than 4 hours after ingestion, do not administer Nephrotect (Acetylcysteine) because there is minimal risk of hepatotoxicity.

	Figure 1: Rumack-Matthew Nomogram for Estimating Potential for Hepatotoxicity from Acetaminophen Poisoning – Plasma or Serum Acetaminophen Concentration versus Time (hours) Post-acetaminophen Ingestion (Adapted from Rumack and Matthew, Pediatrics 1975; 55:871−876.)

Figure 1

Maintenance Dose

Determine need for continued treatment with Nephrotect (Acetylcysteine) after the loading dose. Choose ONE of the following based on the acetaminophen concentration:

The acetaminophen concentration is above the possible toxicity line according to the nomogram :

• Continue Nephrotect (Acetylcysteine) treatment with the maintenance dose for 17 doses .
• Monitor hepatic and renal function and electrolytes throughout treatment.

The acetaminophen concentration could not be obtained:

• Continue Nephrotect (Acetylcysteine) treatment with the maintenance dose for 17 doses .
• Monitor hepatic and renal function and electrolytes throughout treatment.

For patients whose acetaminophen concentration is below the "possible" toxicity line and time of ingestion is known and the sample was obtained more than 4 hours after ingestion:

• Discontinue Nephrotect (Acetylcysteine).

The acetaminophen concentration was in the non-toxic range, but time of ingestion was unknown or less than 4 hours:

• Obtain a second sample for acetaminophen concentration and consider the patient's clinical status to decide whether or not to continue Nephrotect (Acetylcysteine) treatment.
• If there is any uncertainty as to patient's risk of developing hepatotoxicity, it is recommended to administer a complete treatment course under medical observation with appropriate monitoring.

Continued Therapy After Completion of Loading and Maintenance Doses

In cases of suspected massive overdose, or with concomitant ingestion of other substances, or in patients with preexisting liver disease; the absorption and/or the half-life of acetaminophen may be prolonged. In such cases, consideration should be given to the need for continued treatment with Nephrotect (Acetylcysteine) beyond a total of 17 maintenance doses.

Acetaminophen levels and ALT/AST and INR should be checked after the last maintenance dose. If acetaminophen levels are still detectable, or if the ALT/AST are still increasing or the INR remains elevated; the maintenance doses should be continued and the treating physician should contact a US regional poison center at 1-800-222-1222, or alternatively, a "special health professional assistance line for acetaminophen overdose" at 1-800-525-6115 for assistance with dosing recommendations.

2.3 Recommended Dosage and Preparation and Administration Instructions in Adults and Pediatrics for Acute Acetaminophen Ingestion

• Nephrotect is for oral administration only; not for nebulization or intratracheal instillation.
• After appropriate preparation and dilution, Nephrotect (Acetylcysteine) is interchangeable with 20% Nephrotect (Acetylcysteine) solution, when given at the same Nephrotect (Acetylcysteine) dosage.
• Adults and Pediatrics: The recommended loading dose of Nephrotect (Acetylcysteine) is 140 mg/kg. Administer a first maintenance dose of 70 mg/kg 4 hours after the loading dose. Repeat 70 mg/kg maintenance dose every 4 hours for a total of 17 maintenance doses.

Preparation and Administration Instructions

• Dissolve the appropriate number of 2.5 gram and/or 500 mg Nephrotect (Acetylcysteine) effervescent tablets in the volume of water indicated in dosing tables and text below, based upon patient weight.
• Once the tablets are dissolved, administer the oral solution immediately.
• Solutions should be freshly prepared for each dose and utilized within 2 hours.
• If the patient vomits an oral dose of Nephrotect (Acetylcysteine) within 1 hour of administration, repeat that dose.
• If the patient is persistently unable to retain the orally administered Nephrotect (Acetylcysteine), Nephrotect (Acetylcysteine) may be administered by nasoduodenal tube. An intravenous formulation of Nephrotect (Acetylcysteine) may also be considered.

Patients Weighing 20 kg and Greater

Tables 1 and 2 provide the weight-based loading and maintenance doses, respectively, of Nephrotect (Acetylcysteine) for patients weighing 20 kg and greater. For patients weighing 20 to 59 kg dissolve Nephrotect (Acetylcysteine) tablets in 150 mL of water. For patients weighing 60 kg and greater dissolve Nephrotect (Acetylcysteine) tablets in 300 mL of water.

*No specific studies have been conducted to evaluate the necessity of dose adjustments in patients weighing over 100 kg. Limited information is available regarding the dosing requirements of patients that weigh more than 100 kg.
Dissolve Nephrotect (Acetylcysteine) Tablets in 300 mL of Water
Body weight (Kg)	Actual Nephrotect (Acetylcysteine) Dose to be Administered (grams)	Number of Nephrotect (Acetylcysteine) Tablets to Dissolve in Water
		2.5 gram tablets	500 mg tablets
100 or greater	15	6	0
90 to 99	14	5	3
80 to 89	13	5	1
70 to 79	11	4	2
60 to 69	10	4	0
Dissolve Nephrotect (Acetylcysteine) Tablets in 150 mL of Water
50 to 59	8	3	1
40 to 49	7	2	4
30 to 39	6	2	2
20 to 29	4	1	3

Dissolve Nephrotect (Acetylcysteine) Tablets in 300 mL of Water
Body weight (Kg)	Actual Nephrotect (Acetylcysteine) Dose to be Administered (grams)	Number of Nephrotect (Acetylcysteine) Tablets to Dissolve in Water
		2.5 gram tablets	500 mg tablets
100 or greaterNo specific studies have been conducted to evaluate the necessity of dose adjustments in patients weighing over 100 kg. Limited information is available regarding the dosing requirements of patients that weigh more than 100 kg.	7.5	3	0
90 to 99	7	2	4
80 to 89	6.5	2	3
70 to 79	5.5	2	1
60 to 69	5	2	0
Dissolve Nephrotect (Acetylcysteine) Tablets in 150 mL of Water
50 to 59	4	1	3
40 to 49	3.5	1	2
30 to 39	3	1	1
20 to 29	2	0	4

Patients Weighing 1 to 19 kg

Dissolve two 2.5 gram Nephrotect (Acetylcysteine) effervescent tablets in 100 mL of water to create a 50 mg/mL solution. Calculate the loading and maintenance doses using the patient's kilogram weight:

Loading dose: Calculate the dose by multiplying the patient's kilogram weight by 140 mg/kg and dividing by the concentration of the solution (50 mg/mL). The result is the dose in mL for administration using an oral syringe.

Maintenance dose: Calculate the dose by multiplying the patient's kilogram weight by 70 mg/kg and dividing by the concentration of the solution (50 mg/mL). The result is the dose in mL for administration using an oral syringe.

2.4 Recommendations for Repeated Supratherapeutic Acetaminophen Ingestion

Repeated supratherapeutic acetaminophen ingestion (RSI) is an ingestion of acetaminophen at dosages higher than those recommended for extended periods of time. The risk of hepatotoxicity and the recommendations for treatment of acute acetaminophen ingestion (i.e., the Rumack-Matthew nomogram) do not apply to patients with RSI. Therefore, obtain the following information to guide Nephrotect (Acetylcysteine) treatment for RSI.

• Acetaminophen serum or plasma concentrations. A reported history of the quantity of acetaminophen ingested is often inaccurate and is not a reliable guide to therapy.
• Laboratory tests to monitor hepatic and renal function and electrolyte and fluid balance: AST, ALT, bilirubin, INR, creatinine, BUN, blood glucose, and electrolytes.

For specific Nephrotect (Acetylcysteine) dosage and administration information in patients with RSI, consider contacting your regional poison center at 1-800-222-1222, or alternatively, a special health professional assistance line for acetaminophen overdose at 1-800-525-6115.

3 DOSAGE FORMS AND STRENGTHS

Nephrotect (Acetylcysteine) effervescent tablets are supplied as white, round, flat tablets with a lemon mint flavor in the following dosage strengths:

• 500 mg tablets debossed with "I" on one side.
• 2.5 gram tablets debossed with "O" on one side.

Nephrotect (Acetylcysteine) tablets contain the inactive ingredient sodium bicarbonate which may be clinically relevant in some patients .

Effervescent tablets: 500 mg and 2.5 grams (3)

4 CONTRAINDICATIONS

None.

None (4)

5 WARNINGS AND PRECAUTIONS

• Hypersensitivity Reactions, Including Urticaria: Discontinue Nephrotect unless deemed essential to patient management and the reactions can be otherwise controlled. (5.1)
• Risk of Upper Gastrointestinal Hemorrhage: Consider the risk/benefit for patients at risk of hemorrhage (e.g., those with esophageal varices, peptic ulcers, etc.) versus the risk of developing hepatic toxicity, and treat with Nephrotect (Acetylcysteine) accordingly.(5.2)

5.1 Hypersensitivity Reactions

Hypersensitivity reactions, including generalized urticaria have been observed in patients receiving oral Nephrotect (Acetylcysteine) for acetaminophen overdose. If hypersensitivity reactions occur, Nephrotect (Acetylcysteine) should be discontinued unless it is deemed essential for patient management and the reactions can be otherwise controlled.

5.2 Risk of Upper Gastrointestinal Hemorrhage

Occasionally severe and persistent vomiting occurs as a symptom of acute acetaminophen overdose. Treatment with Nephrotect (Acetylcysteine) may aggravate the vomiting and increase the risk of upper gastrointestinal hemorrhage in at risk patients (e.g., those with esophageal varices, peptic ulcers, etc.). Consider the risk/benefit for patients at risk of hemorrhage versus the risk of developing hepatic toxicity, and treat with Nephrotect (Acetylcysteine) as needed.

6 ADVERSE REACTIONS

The following adverse reactions are described, or described in greater detail, in other sections of the labeling:

• Hypersensitivity Reactions
• Risk for Upper Gastrointestinal Hemorrhage

The most common adverse reactions have been identified from clinical studies or postmarketing reports of Nephrotect (Acetylcysteine). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The most common adverse reactions were nausea, vomiting, other gastrointestinal symptoms, and rash with or without fever.

Most common adverse reactions are nausea and vomiting, other gastrointestinal symptoms, and rash with or without fever. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Arbor Pharmaceuticals LLC at 1- 866-516-4950 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Limited published case reports and case series on Nephrotect use during pregnancy are insufficient to inform a drug-associated risk of birth defects and miscarriage. However, there are clinical considerations . In animal reproduction studies, no teratogenic effects were observed with oral administration of Nephrotect (Acetylcysteine) to pregnant rats and rabbits during organogenesis at doses up to 0.6 times the maximum recommended human dose (based on body surface area) of about 560 mg/kg (total dose on first day of treatment) .

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Acetaminophen and Nephrotect (Acetylcysteine) cross the placenta. Delaying treatment in pregnant women with acetaminophen overdose and potentially toxic acetaminophen plasma levels may increase the risk of maternal and fetal morbidity and mortality.

Data

Animal Data

No teratogenic effects were observed in embryo-fetal development studies in rats at oral doses up to 2000 mg/kg/day (0.6 times the maximum recommended human dose based on body surface area) or in rabbits at oral doses up to 1000 mg/kg/day (0.6 times the maximum recommended human dose based on body surface area) administered during organogenesis.

8.2 Lactation

Risk Summary

There is no information regarding the presence of Nephrotect (Acetylcysteine) in human milk, or the effects of Nephrotect (Acetylcysteine) on the breastfed infant or on milk production. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for Nephrotect (Acetylcysteine) and any potential adverse effects on the breastfed infant from Nephrotect (Acetylcysteine) or from the underlying maternal condition.

8.4 Pediatric Use

Pediatric approval, including dosing, is not based on adequate and well-controlled clinical studies. Pediatric dosing recommendations are based on clinical experience .

8.5 Geriatric Use

Clinical studies of Nephrotect (Acetylcysteine) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience with Nephrotect (Acetylcysteine) has not identified differences in the 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.

8.6 Patients Sensitive to High Sodium Intake

Nephrotect (Acetylcysteine) tablets contain sodium. Consider the total sodium content from dietary and non-dietary sources in patients who may be sensitive to excess sodium intake, such as those with congestive heart failure, hypertension, or renal impairment.

At the recommended dosage an average sized adult (60 kg) may receive a total of 7 grams of sodium (304.3 mEq) on the first day of treatment, 5.3 grams of sodium (230.4 mEq) on the second day of treatment, and 4.4 grams of sodium (191.3 mEq) on the third day of treatment.

If sodium intake is a concern, please refer to Table 3 for the amount of sodium in each tablet and to Tables 1 and 2 for the recommended dosage in adults and pediatrics based on body weight in order to calculate the amount of sodium administered to an individual patient .

11 DESCRIPTION

Nephrotect (Acetylcysteine) is an antidote for the treatment of acetaminophen overdose. It is the N-acetyl derivative of the naturally-occurring amino acid, cysteine. Nephrotect (Acetylcysteine) is a white crystalline powder that is freely soluble in water, alcohol, practically insoluble in chloroform and in ether with the molecular formula C₅H₉NO₃S, a molecular weight of 163.2, and chemical name of N-acetyl-L-cysteine. Nephrotect (Acetylcysteine) has the following structural formula:

Nephrotect (Acetylcysteine) (acetylcysteine) effervescent tablets for oral solution contain 500 mg or 2.5 grams of Nephrotect (Acetylcysteine). The following are inactive ingredients: sodium bicarbonate, maltodextrin, lemon flavor, sucralose, peppermint flavor, and edetate disodium.

The amount of sodium in each tablet of Nephrotect (Acetylcysteine) is shown in Table 3.

Tablet Strength	Sodium Bicarbonate (mg)inactive ingredient	Sodium (mg)	Sodium (mEq)
500 mg	320 mg	88 mg	3.8 mEq
2.5 grams	1600 mg	438 mg	19 mEq

Chemical Structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Nephrotect has been shown to reduce the extent of liver injury following acetaminophen overdose. Acetaminophen doses of 150 mg/kg or greater have been associated with hepatotoxicity. Nephrotect (Acetylcysteine) probably protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite of acetaminophen.

12.3 Pharmacokinetics

Absorption

After administration of a single oral dose of 11 grams of Nephrotect (Acetylcysteine) (dissolved in 300 mL of water) to 29 healthy adult subjects, the mean C_max (CV%) was 26.5 (29) mcg/mL and mean (CV) AUC_inf was 186 (29) hr∙mcg/mL. The median (range) time to reach C_max (T_max) was 2 (1 to 3.5) hours.

Distribution

The steady-state volume of distribution (V_d) following administration of an intravenous dose of Nephrotect (Acetylcysteine) was 0.47 liter/kg. The protein binding for Nephrotect (Acetylcysteine) ranges from 66% to 87 %.

Elimination

Metabolism

Nephrotect (Acetylcysteine) (i.e., N-acetylcysteine) undergoes extensive first pass metabolism and is postulated to form cysteine and disulfides (N,N-diacetylcysteine and N-acetylcysteine). Cysteine is further metabolized to form glutathione and other metabolites.

Excretion

After a single oral dose of [³⁵S]-acetylcysteine 100 mg, between 13 to 38% of the total radioactivity administered was recovered in urine within 24 hours. In a separate study, renal clearance was estimated to be approximately 30% of total body clearance.

In healthy subjects given a single oral dose of 11 grams of Nephrotect (Acetylcysteine), the mean (CV%) terminal plasma half-life (T_1/2) was 18.1 (22%) hours.

Specific Populations

Hepatic Impairment

Following a 600 mg intravenous dose of Nephrotect (Acetylcysteine) to subjects with mild (Child Pugh Class A, n=1), moderate (Child-Pugh Class B, n=4) or severe (Child-Pugh Class C; n=4) hepatic impairment and 6 healthy matched controls, mean T_1/2 increased by 80%. Also, the mean CL decreased by 30% and the systemic Nephrotect (Acetylcysteine) exposure (mean AUC) increased 1.6-fold in subjects with hepatic impairment compared to subjects with normal hepatic function. These changes are not considered to be clinically meaningful.

Renal Impairment

Hemodialysis may remove some of total Nephrotect (Acetylcysteine).

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Carcinogenicity studies in laboratory animals have not been performed with Nephrotect (Acetylcysteine).

Mutagenesis

Nephrotect (Acetylcysteine) was negative in the Ames test.

Impairment of Fertility

In a fertility study of Nephrotect (Acetylcysteine) in rats, intravenous administration of 1000 mg/kg/day (0.3 times the recommended human oral dose based on body surface area) caused a profound reduction of fertility in females, which was correlated with morphological changes in oocytes and severe impairment of implantation (18 of 20 mated females had no implantations). The reversibility of this effect was not evaluated. No effects on fertility were observed in female rats at intravenous doses up to 300 mg/kg/day (0.1 times the recommended human oral dose based on body surface area), or in male rats at intravenous doses up to 1000 mg/kg/day. Mating was unaffected in this study.

In a reproduction study of Nephrotect (Acetylcysteine), male rats were treated orally for 15 weeks prior to mating and during the mating period. A slight non-dose related reduction in fertility was observed at oral doses of 500 and 1000 mg/kg/day (0.1 and 0.3 times the recommended human dose, respectively, based on body surface area).

16 HOW SUPPLIED/STORAGE AND HANDLING

Nephrotect (Acetylcysteine) effervescent tablets are supplied as white, round, flat tablets with a lemon mint smell packaged in 2-count peelable foil blister packs in the following dosage strengths:

• 500 mg tablets debossed with "I" on one side; Each carton containing 2-count blister packs (24338-700-02)
  • NDC 24338-700-10: 10 pack carton containing 20 tablets
• 2.5 gram tablets debossed with "O" on one side; Each carton containing 2-count blister packs (24338-725-02)
  • NDC 24338-725-10: 10 pack carton containing 20 tablets

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) Protect from moisture. Store tablets in original blister package until use.

Dilutions of Nephrotect (Acetylcysteine) should be used freshly prepared and utilized within two hours.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Hypersensitivity Reactions

Advise patients that hypersensitivity reactions, including generalized urticaria may occur and to report any signs or symptoms to their healthcare provider immediately .

Manufactured for:

arbor

PHARMACEUTICALS, LLC

Atlanta, GA 30328

Made in Switzerland by Alpex Pharma SA.

CET-PI-02

Rev. 04/2017

Patient Information Nephrotect (Acetylcysteine)® (SEE-tuh-lev) (acetylcysteine) effervescent tablets for oral solution
What is Nephrotect (Acetylcysteine)? Nephrotect (Acetylcysteine) is a prescription medicine used to prevent or lessen liver damage in people who have taken too much acetaminophen (overdose).
Before taking Nephrotect (Acetylcysteine), tell your healthcare provider about all of your medical conditions, including if you: have or have had bleeding in your esophagus (esophageal varices). have or have had stomach ulcers. have high blood pressure, kidney or heart problems, or have been told to lower the amount of salt (sodium) in your diet. are pregnant or plan to become pregnant. It is not known if Nephrotect (Acetylcysteine) will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if Nephrotect (Acetylcysteine) passes into your breast milk and may harm your baby. You and your healthcare provider should decide if you will take Nephrotect (Acetylcysteine) or breastfeed. You should not do both. Tell your healthcare provider about all the medicines you take including prescription and over-the-counter medicines, vitamins and herbal supplements.
How should I take Nephrotect (Acetylcysteine)? Take Nephrotect (Acetylcysteine) exactly as your healthcare provider tells you to. Your healthcare provider will tell you how much Nephrotect (Acetylcysteine) to take and when to take it. Do not stop taking Nephrotect (Acetylcysteine) unless your healthcare provider tells you to. Your healthcare provider may change your dose if needed. Nephrotect (Acetylcysteine) tablets should be dissolved in water before taking. Do not take Nephrotect (Acetylcysteine) tablets until they are dissolved in water. Nephrotect (Acetylcysteine) should only be taken by mouth and after being dissolved in water.
What are the possible side effects of Nephrotect (Acetylcysteine)? Nephrotect (Acetylcysteine) may cause serious side effects, including: allergic reactions. Stop taking Nephrotect (Acetylcysteine) and tell your healthcare provider right away if you have any signs and symptoms of an allergic reaction including: rash, hives, swelling of your face, eyes, lips, tongue or throat, trouble swallowing or breathing risk of bleeding in your esophagus and stomach The most common side effects of Nephrotect (Acetylcysteine) include: nausea, vomiting, stomach problems, rash (with or without a fever) These are not all of the possible side effects of Nephrotect (Acetylcysteine). Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Nephrotect (Acetylcysteine)? Store Nephrotect (Acetylcysteine) at room temperature between 68°F to 77°F (20°C to 25°C). Keep Nephrotect (Acetylcysteine) and all medicines out of reach of children.
General information about the safe and effective use of Nephrotect (Acetylcysteine). Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Nephrotect (Acetylcysteine) for a condition for which it was not prescribed. Do not give Nephrotect (Acetylcysteine) to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for more information about Nephrotect (Acetylcysteine) that is written for health professionals.
What are the ingredients in Nephrotect (Acetylcysteine)? Active ingredient: Nephrotect (Acetylcysteine) Inactive ingredients: sodium bicarbonate, maltodextrin, lemon flavor, sucralose, peppermint flavor, and edetate disodium Manufactured for: arbor PHARMACEUTICALS, LLC Atlanta, GA 30328 Made in Switzerland For more information, call 1-866-516-4950
This Patient Information has been approved by the U.S. Food and Drug Administration	Issued: January 2016

Arginine:

• Nephrotect (Arginine) reviews

Nutritive Wound - Skin Cream

For Minor Cuts and Wounds

- Eases Discomfort

- Soothing Cream

CONTAINS:

Nephrotect (Arginine) Aminobenzoate 2.5% Patent # 5734080

In a cream base with Safflower Oil, Apricot Kernel Oil, Mixed Tocopherols, Glycerin, Coconut Oil, Borage Oil, Tea Tree Oil, Camphor, Thymine, Lecithin, Grapefruit Extract, Lemon Oil and Aloe Vera.

DIRECTIONS:

Apply topically as needed to superficial wounds and abrasions.

INDICATIONS FOR USE:

FelineAid can be used on minor cuts, abrasions and irritations as well as superficial wounds and skin lesions on cats.

CAUTIONS:

Avoid contact with eyes. If contact occurs, flush with copious amounts of water. If condition persists or worsens discontinue use.

Shake Well

Store at room temperature.

For Veterinary Use Only

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• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
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• Nephrotect (Glycine) reviews

INDICATIONS AND USAGE

1.5% Nephrotect (Glycine) Irrigation, USP is indicated for use as irrigating fluid during transurethral prostatic resection and other transurethral surgical procedures.

CONTRAINDICATIONS

NOT FOR INJECTION BY USUAL PARENTERAL ROUTES.

Do not use in patients with anuria.

WARNINGS

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, Nephrotect (Glycine) irrigating solution must be regarded as a systemic drug. Absorption of large amounts of fluids containing Nephrotect (Glycine) may significantly alter cardiopulmonary and renal dynamics.

Do not heat container over 66°C (150°F).

PRECAUTIONS

Cardiovascular status, especially of the patient with cardiac disease, should be carefully observed before and during transurethral resection of the prostate when using Nephrotect (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 Nephrotect (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 Nephrotect (Glycine) Irrigation, USP have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility.

Nursing Mothers: Caution should be exercised when Nephrotect (Glycine) Irrigation, USP is administered to a nursing woman.

Pregnancy: Teratogenic Effects.

Pregnancy Category C. Animal reproduction studies have not been conducted with Nephrotect (Glycine) Irrigation, USP. It is also not known whether Nephrotect (Glycine) Irrigation, USP can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Nephrotect (Glycine) Irrigation, USP should be given to a pregnant woman only if clearly needed.

Pediatric Use: The safety and effectiveness of Nephrotect (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

Adverse reactions may result from intravascular absorption of Nephrotect (Glycine). Large intravenous doses of Nephrotect (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 Nephrotect (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.

OVERDOSAGE

In the event of overhydration or solute overload, re-evaluate the patient and institute appropriate corrective measures. See WARNINGS, PRECAUTIONS and ADVERSE REACTIONS.

DOSAGE AND ADMINISTRATION

1.5% Nephrotect (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.

HOW SUPPLIED

1.5% Nephrotect (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

IM-1453

iv bag ndc 0409-7974-08

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

Lysine Acetate:

• Boxed warning
• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Nephrotect (Lysine Acetate) reviews

BOXED WARNING

Pharmacy Bulk Package

Not For Direct Infusion

DESCRIPTION

Nephrotect (Lysine Acetate)^® 15% Amino Acids Injection in a Pharmacy Bulk Package is a sterile, clear, nonpyrogenic solution of essential and nonessential amino acids for intravenous infusion in parenteral nutrition following appropriate dilution.

Nephrotect (Lysine Acetate)^® 15% in a Pharmacy Bulk Package is not for direct infusion. It is a sterile dosage from which contains several single doses for use in a pharmacy admixture program in the preparation of intravenous parenteral fluids.

Each 100 mL contains:

Essential Amino Acids
Nephrotect (Lysine Acetate) (from Nephrotect (Lysine Acetate) Acetate, USP)……………………………………...1.18		g
Leucine, USP……………………………………………………………...1.04		g
Phenylalanine, USP……………………………………...1.04		g
Valine, USP……………………………………………………………...960		mg
Isoleucine, USP………………………………………...749		mg
Methionine, USP………………………………………...749		mg
Threonine, USP………………………………………...749		mg
Tryptophan, USP………………………………………...250		mg
Nonessential Amino Acids
Alanine, USP…………………………………………...2.17		g
Arginine, USP…………………………………………...1.47		g
Glycine, USP…………………………………………...1.04		g
Histidine, USP…………………………………………...894		mg
Proline, USP……………………………………………………………...894		mg
Glutamic Acid…………………………………………...749		mg
Serine, USP……………………………………………...592		mg
Aspartic Acid, USP……………………………………...434		mg
Tyrosine, USP…………………………………………...39		mg
Sodium Metabisulfite, NF added……………………………………………...30		mg
Water for Injection, USP……………………………………………………...		qs
Essential Amino Acids………………………………………………………...6.7		g
Nonessential Amino Acids…………………………………………………...8.3		g
Total Amino Acids…………………………………………………………...15.0		g
Total Nitrogen………………………………………………………………...2.37		g
Acetate*……………………………………………………...151		mEq/L
Osmolarity (calculated)……………………………………...1388		mOsmol/L
pH……………………………………………………………………………...5.6(5.2-6.0)
*Acetate from Nephrotect (Lysine Acetate) Acetate, USP and acetic acid used for pH adjustment.

The formulas for the individual amino acids are as follows:

Formulas for individual amino acids

CLINICAL PHARMACOLOGY

Nephrotect (Lysine Acetate)^® 15% Amino Acids Injection providesseventeen crystalline amino acids. This completely utilizable substrate promotesprotein synthesis and wound healing and reduces the rate of protein catabolism.

A.Total Parenteral Nutrition (Central Infusion)

When enteralfeeding is inadvisable, Nephrotect (Lysine Acetate)^® 15% given by central venousinfusion in combination with energy sources, vitamins, trace elements andelectrolytes, will completely satisfy the requirements for weight maintenanceor weight gain, depending upon the dose selected. The energy component inparenteral nutrition by central infusion may be derived solely from dextroseor may be provided by a combination of dextrose and intravenous fat emulsion. The addition of intravenous fat emulsion provides essential fatty acids andpermits a dietary balance of fat and carbohydrate, at the same time offeringthe option of reducing the dextrose load and/or increasing the total caloricinput. An adequate energy supply is essential for optimal utilization of aminoacids.

B. Total Parenteral Nutrition (Peripheral Infusion)

Nephrotect (Lysine Acetate)^® 15%can also be administered as part of a total parenteral nutrition program byperipheral vein when the enteral route is inadvisable and use of the centralvenous catheter is contraindicated.

Reduction of proteinloss can be achieved by use of diluted Nephrotect (Lysine Acetate)^® 15% in combinationwith dextrose or with dextrose and intravenous fat emulsion by peripheralinfusion. Complete peripheral intravenous nutrition can be achieved in patientswith low caloric requirements by a Nephrotect (Lysine Acetate)^®15%-dextrose-fatregimen.

INDICATIONS AND USAGE

Nephrotect (Lysine Acetate)^® 15% is indicated as an amino acid(nitrogen) source in parenteral nutrition regimens. This use is appropriatewhen the enteral route is inadvisable, inadequate or not possible, as when:

-Gastrointestinal absorption is impaired by obstruction, inflammatory diseaseor its complications, or antineoplastic therapy;

-Bowel rest is needed because of gastrointestinal surgery or its complicationssuch as ileus, fistulae or anastomotic leaks;

-Tube feeding methods alone cannot provide adequate nutrition.

CONTRAINDICATIONS

This solution should not be used in patients in hepatic coma,severe renal failure, metabolic disorders involving impaired nitrogen utilizationor hypersensitivity to one or more amino acids.

WARNINGS

Administration of amino acids solutions at excessive ratesor to patients with hepatic insufficiency may result in plasma amino acidimbalances, hyperammonemia, prerenal azotemia, stupor and coma. Conservativedoses of amino acids should be given to these patients, dictated by the nutritionalstatus of the patient. Should symptoms of hyperammonemia develop, amino acidadministration should be discontinued and the patient’s clinical statusre-evaluated.

Contains sodium metabisulfite, a sulfitethat may cause allergic-type reactions including anaphylactic symptoms andlife-threatening or less severe asthmatic episodes in certain susceptiblepeople. The overall prevalence of sulfite sensitivity in the general populationis unknown and probably low.

Sulfite sensitivity isseen more frequently in asthmatic than in nonasthmatic people.

WARNING: This product contains aluminum that maybe toxic. Aluminum may reach toxic levels with prolonged parenteral administrationif kidney function is impaired. Premature neonates are particularly at riskbecause their kidneys are immature, and they require large amounts of calciumand phosphate solutions, which contain aluminum.

Researchindicates that patients with impaired kidney function, including prematureneonates, who receive parenteral levels of aluminum at greater than 4 to 5mcg/kg/day accumulate aluminum at levels associated with central nervous systemand bone toxicity. Tissue loading may occur at even lower rates of administration.

PRECAUTIONS

A. GENERAL

It is essential to provide adequate calories concurrently if parenterally administered amino acids are to be retained by the body and utilized for protein synthesis.

The administration of Nephrotect (Lysine Acetate)^® 15% Amino Acids Injection as part of total parenteral nutrition (TPN) with large volumes of hyperosmotic fluids requires periodic monitoring of the patient for signs of hyperosmolarity, hyperglycemia, glycosuria and hypertriglyceridemia.

During parenteral nutrition with concentrated dextrose and amino acids solutions, essential fatty acid deficiency syndrome may develop but may not be clinically apparent. Early demonstration of this condition can only be accomplished by gas liquid chromatographic analysis of plasma lipids. The syndrome may be prevented or corrected by appropriate treatment with intravenous fat emulsions.

For complete nutritional support, TPN regimens must also include multiple vitamins and trace elements. Potentially incompatible ions such as calcium and phosphate may be added to alternate infusate bottles to avoid precipitation. Although the metabolizable acetate ion in Nephrotect (Lysine Acetate)^® 15% diminishes the risk of acidosis, the physician must be alert to the potential appearance of this disorder.

Initiation and termination of infusions of TPN fluids must be gradual to permit adjustment of endogenous insulin release.

Undiluted Nephrotect (Lysine Acetate)^® 15% should not be administered peripherally. When administered centrally, it should be diluted with appropriate diluents, e.g., dextrose, electrolytes and other nutrient components, to at least half strength. See DOSAGE AND ADMINISTRATION.

Caution against volume overload should be exercised.

Drug product contains no more than 25 mcg/L of aluminum.

B. Laboratory Tests

Infusion of Nephrotect (Lysine Acetate)^® 15% without concomitant infusion of an adequate number of non-protein calories may result in elevated BUN. Monitoring of BUN is required and the balance between Nephrotect (Lysine Acetate)^® 15% and the calorie source may require adjustment. Frequent clinical evaluations and laboratory determinations are required to prevent the complications which may occur during the administration of solutions used in TPN. Laboratory tests should include blood glucose, serum electrolytes, liver and kidney function, serum osmolarity, blood ammonia, serum protein, pH, hematocrit, WBC and urinary glucose. When Nephrotect (Lysine Acetate)^® 15% is combined with electrolytes, care should be used in administering this solution to patients with congestive heart failure, renal failure, edema, adrenal hyperactivity, acid-base imbalance and those receiving diuretics or antihypertensive therapy. Total volume infused should be closely monitored. Serum electrolytes should be monitored daily in these patients.

C. Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with Nephrotect (Lysine Acetate)^® 15% have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility.

D. Pregnancy Category C

Animal reproduction studies have not been conducted with Nephrotect (Lysine Acetate)^® 15%. It is also not known whether Nephrotect (Lysine Acetate)^® 15% can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Nephrotect (Lysine Acetate)^® 15% should be given to a pregnant woman only if clearly needed.

E. Nursing Mothers

Caution should be exercised when Nephrotect (Lysine Acetate)^® 15% is administered to a nursing woman.

F. Pediatric Use

Safety and effectiveness of Nephrotect (Lysine Acetate)^® 15% Amino Acids Injection in pediatric patients have not been established by adequate and well-controlled studies. However, the use of amino acids injections in pediatric patients as an adjunct in the offsetting of nitrogen loss or in the treatment of negative nitrogen balance is referenced in the medical literature.

G. Special Precautions for Central Infusion

TPN delivered by indwelling catheter through a central or large peripheral vein is a special technique requiring a team effort by physician, nurse and pharmacist. The responsibility for administering this therapy should be confined to those trained in the procedures and alert to signs of complications. Complications known to occur from the placement of central venous catheter are pneumothorax, hemothorax, hydrothorax, artery puncture and transection, injury to the brachial plexus, malposition of the catheter, formation of arteriovenous fistula, phlebitis, thrombosis, and air/catheter emboli. The risk of sepsis is present during intravenous therapy, especially when using central venous catheters for prolonged periods. It is imperative that the preparation of admixtures and the placement and care of the catheters be accomplished under controlled aseptic conditions.

H. Admixtures

Admixtures should be prepared under a laminar flow hood using aseptic technique.

Admixtures should be stored under refrigeration and must be administered within 24 hours after removal from refrigerator.

Filters of less than 1.2 micron pore size must not be used with admixtures containing fat emulsion.

I. Do not administer unless solution is clear and the seal is intact.

IT IS ESSENTIAL THAT A CAREFULLY PREPARED PROTOCOL, BASED ON CURRENT MEDICAL PRACTICES, BE FOLLOWED, PREFERABLY BY AN EXPERIENCED TEAM.

ADVERSE REACTIONS

OVERDOSAGE

In the event of overhydration or solute overload, re-evaluatethe patient and institute appropriate corrective measures. See WARNINGS andPRECAUTIONS.

DOSAGE AND ADMINISTRATION

The appropriate daily dose of amino acids to be used withdextrose or with dextrose and intravenous fat emulsion will depend upon themetabolic status and clinical response of the patient as therapy proceeds. Doses which achieve nitrogen equilibrium or positive balance are the mostdesirable. The dosage on the first day should be approximately half the anticipatedoptimal dosage and should be increased gradually to minimize glycosuria; similarly,withdrawal should be accomplished gradually to avoid rebound hypoglycemia.

Fatemulsion coadministration should be considered when prolonged (more than 5days) parenteral nutrition is required in order to prevent essential fattyacid deficiency (EFAD). Serum lipids should be monitored for evidence of EFADin patients maintained on fat free TPN.

The amount administeredis dosed on the basis of amino acids/kg of body weight/day. In general, twoto three g/kg of body weight for neonates and infants with adequate caloriesare sufficient to satisfy protein needs and promote positive nitrogen balance. In pediatric patients, the final solution should not exceed twice normal serumosmolarity (718 mOsmol/L).

DIRECTIONSFOR PROPER USE OF PHARMACY BULK PACKAGE

Nephrotect (Lysine Acetate)^® 15%in a Pharmacy Bulk Package is not intended for direct infusion. The containerclosure may be penetrated only once using a suitable sterile transfer deviceor dispensing set which allows measured dispensing of the contents. The PharmacyBulk Package is to be used only in a suitable work area such as a laminarflow hood (or an equivalent clean air compounding area). Once the closureis penetrated, the contents should be dispensed as soon as possible; the transferof contents must be completed within 4 hours of closure entry. The bottlemay be stored at room temperature (25°C) after the closure has been entered. Date and time of container entry should be noted in the area designated onthe container label.

When using Nephrotect (Lysine Acetate)^® 15%in patients with a need for fluid volume restriction, it can be diluted asfollows:

	Volume	Amount	FinalConcentration
Nephrotect (Lysine Acetate)® 15%	500 mL	75 g	7.5%
Dextrose 70%	250 mL	175 g	17.5%
Intralipid® 20%	250 mL	50 g	5.0%

This will provide 1395 kilocalories (kcal) per 1000 mLof admixture with a ratio of 118 non-protein calories per gram of nitrogenand an osmolarity of 1561 mOsmol/L.

In patients wherethe need for fluid restriction is not so marked, either of the following regimensmay be used dependent upon the energy needs of the patient.

	Volume	Amount	FinalConcentration
Nephrotect (Lysine Acetate)® 15%	500 mL	75 g	3.75%
Dextrose 50%	1000 mL	500 g	25%
Intralipid® 20%	500 mL	100 g	5%

This will provide 1500 kcal per 1000 mL of admixture witha ratio of 228 non-protein calories per gram of nitrogen and an osmolarityof 1633 mOsmol/L.

	Volume	Amount	FinalConcentration
Nephrotect (Lysine Acetate)® 15%	500 mL	75 g	3.75%
Dextrose 30%	1000 mL	300 g	15%
Intralipid® 10%	500 mL	50 g	2.5%

This will provide 935 kcal per 1000 mL of admixture witha ratio of 158 non-protein calories per gram of nitrogen and an osmolarityof 1128.5 mOsmol/L.

A. Total Parenteral Nutrition (CentralInfusion)

In unstressed adult patients with no unusualnitrogen losses, a minimum dosage of 0.1 gram nitrogen (4.2 mL of Nephrotect (Lysine Acetate)^® 15%)plus 4.4 grams (15 calories) of dextrose per kilogram of body weight per dayare required to achieve nitrogen balance and weight stability. Intravenousfat emulsion may be used as a partial substitute for dextrose. This regimenprovides a ratio of 150 non-protein calories per gram of nitrogen.

Forpatients stressed by surgery, trauma or sepsis, and those with unusual nitrogenlosses, the dosage required for maintenance may be as high as 0.3 to 0.4 gramsof nitrogen (13 to 17 mL Nephrotect (Lysine Acetate)^® 15%) per kilogram of bodyweight per day, with proportionate increases in non-protein calories. Periodicassessment of nitrogen balance of the individual patient is the best indicatorof proper dosage. Volume overload and glycosuria may be encountered at highdosage, and nitrogen balance may not be achieved in extremely hypermetabolicpatients under these constraints. Concomitant insulin administration may berequired to minimize glycosuria. Daily laboratory monitoring is essential.

Useof an infusion pump is advisable to maintain a steady infusion rate duringcentral venous infusion.

B. Peripheral Nutrition

Inpatients for whom central venous catheterization is not advisable, proteincatabolism can be reduced by peripheral use of diluted Nephrotect (Lysine Acetate)^® 15%plus non-protein calorie sources. Dilution of 250 mL Nephrotect (Lysine Acetate)^® 15%in 750 mL of 10% dextrose will reduce the osmolarity to a level (724 mOsmol/L)which is more favorable to the maintenance of the integrity of the walls ofthe veins. Intravenous fat emulsion can be infused separately or simultaneously;if infused simultaneously the fat emulsion will provide a dilution effectupon the osmolarity while increasing the energy supply.

Parenteraldrug products should be inspected visually for particulate matter and discolorationprior to administration, whenever solution and container permit.

Toreduce the risk of bacterial contamination, all intravenous administrationsets should be replaced at least every 24 hours. Usage of admixtures mustbe initiated within 24 hours after mixing. If storage is necessary duringthis 24 hour period, admixtures must be refrigerated and completely used within24 hours of beginning administration.

HOW SUPPLIED

Nephrotect (Lysine Acetate)^® 15% Amino Acids Injection is suppliedas a Pharmacy Bulk Package in 500 mL containers.

500mL NDC 0409-0468-05

STORAGE

Store inthe closed carton; do not expose solution to light until ready for use. Exposureof pharmaceutical products to heat should be minimized. Avoid excessive heat. It is recommended that the product be stored at 20 to 25°C (68 to 77°F). Brief exposure to temperatures above25°C during transport and storage will not adversely affect the product. Solution that has been frozen must not be used.

©Hospira 2005	EN-1010

Hospira, Inc., Lake Forest, IL 60045 USA

RL-1450

Tryptophan:

• Nephrotect (Tryptophan) reviews

In Canada, Nephrotect (Tryptophan) is sold as a prescription drug to treat mood disorders (such as bipolar disorder, depression ). It is usually used with other medicines. It works to make the mood more stable and reduce extremes in behavior by restoring the balance of certain natural substances (serotonin, melatonin ) in the brain. Nephrotect (Tryptophan) is a natural substance (amino acid) found in high-protein foods and milk. In the US, Nephrotect (Tryptophan) is sold as a dietary supplement. It has been used to support mood, relaxation, and restful sleep. If you are taking other medications that may affect serotonin (such as many antidepressants ), do not take Nephrotect (Tryptophan) without talking with your doctor first. A very serious (possibly fatal) drug interaction may occur. Your doctor should closely monitor you. See also Side Effects section. Some supplement products have been found to contain possibly harmful impurities/additives. Check with your pharmacist for more details about the brand you use. The US FDA has not reviewed this product for safety or effectiveness. Consult your doctor or pharmacist for more details.