Acetadote (acetylcysteine) Injection Package Insert, page of Item info. These highlights do not include all the info. needed to use Acetadote safely and effectively. See full prescribing info. for Acetadote. ACETADOTE (acetylcysteine) Injection Initial U.S. Approval: 2004 RECENT MAJOR CHANGES Adverse Reactions, Postmarketi ng Safety Study 12/2008 INDICATIONS AND USAGE Acetadote, administered intravenously ithin to 10 hours after ingestion of potentially hepatotoxic quantity of acetam inophen, is indicated to prevent or lessen hepatic injury --DOSAGE AND ADMINISTRATION - Patients 40 kg : Loading Dose: 150 mg/kg in 200 mL of diluent administered over 60 min Dose 2: 50 mg/kg in 500 mL of diluent administered over hr Dose 3: 100 mg/kg in 1000 mL of diluent administered over 16 hr Patients >20- <40 kg : Loading Dose: 150 mg/kg in 100 mL of diluent administered over 60 min Dose 2: 50 mg/kg in 250 mL of diluent administered over hr Dose 3: 100 mg/kg in 500 mL of diluent administered over 16 hr Patients 20 kg : Loading Dose: 150 mg/kg in mL/kg of bo dy weight of diluent administered over 60 min Dose 2: 50 mg/kg in mL/kg of body we ight of diluent administered over hr Dose 3: 100 mg/kg in 14 mL/kg of body weight of diluent administered over 16 hr -DOSAGE FORMS AND STRENGTHS Vials: 200 mg/mL, 30 mL (20% solution) --CONTRAINDICATIONS -- Patients with previous anaphylactoid reaction to acetylcysteine WARNINGS AND PRECAUTIONS ? Monitor as acute flushing and erythema of the skin may occur; usually associated with the loading dose; of ten resolves spontaneously despite continued infusion Monitor for serious anaphylactoid reac tions; infusion may be interrupted until treatment of anaphylactoid symp toms has been initiated Should be used with caution in patients with asthma, or where there is history of bronchospasm Total volume administered should be ad justed for patients less than 40kg and for those requiring fluid restriction --ADVERSE REACTIONS - Most common adverse reactions (incidence >2%) are rash, urticaria/facial flushing and pruritus To report SUSPECTED ADVERSE REACTIONS, contact Cumberland Pharmaceuticals Inc. at 1-877-484-2700 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch --DRUG INTERACTIONS - No drug-drug interaction studies have been conducted. USE IN SPECIFIC POPULATIONS Pregnancy: This drug should be used dur ing pregnancy only if clearly needed Nursing Mothers: Unknown if drug is excreted in human milk Pediatric Use: See dose adjustment for patients 40 kg See 17 for PATIENT COUNSELING info. Revised: 12/2008 FULL Item info.: CONTENTS* INDICATIONS AND USAGE 1.1 Acetaminophen Assays Interp retation and Methodology Acute Ingestion 1.2 Acetaminophen Assays In terpretation and Methodology Repeated Supratherapeutic Ingestion DOSAGE AND ADMINISTRATION 2.1 Administration Instructions (T hree-Bag Method: Loading, Second and Third dose) 2.2 Renal Impairment 2.3 Hepatic Impairment DOSAGE FORMS AND STRENGTHS CONTRAINDICATIONS WARNINGS AND PRECAUTIONS 5.1 Anaphylactoid Reactions 5.2 Monitoring Patients with Asthma 5.3 Volume Adjustment: Patients <40kg and Requiring Fluid Restriction ADVERSE REACTIONS 6.1 Clinical Studies Experience DRUG INTERACTIONS USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.3 Nursing mothers 8.4 Pediatric use 8.5 Geriatric use 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of action 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagene sis, Impairment of Fertility 13.3 Reproductive and Developmental Toxicology 14 CLINICAL STUDIES 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING info. *Sections or subsections omitted from th Full Prescribing info. are not listed. Acetadote (acetylcysteine) Injection Package Insert, page of FULL Item info. INDICATIONS AND USAGE Acetadote, administered intr avenously within to 10 hours after ingestion of potentially hepatotoxic quantity of acetaminophen, is indicated to pr event or lessen hepatic injury see Dosage and Administration and Acetaminophen Assays Interpretation and Methodology (1.1, 1.2) ]. On admission for suspected acetaminophen overdose, serum blood sample should be drawn at least hours after ingestion to determine the acetaminophen level and will serve as basis for determining the need for treatment with acetylcysteine. If the patient pr esents after hours post- ingestion, the serum acetaminophen sample should be determined immediately. Acetadote should be administered within hours from acetaminophen ingestion for maximal protection against hepatic injury for patients whose serum acetaminophen levels fall above the ?possible? toxicity line on the Rumack-Matthew nomogram (line connecting 150 mcg/mL at hours with 37.5 mcg/mL at 12 hours); see Acetaminophen Assays Interpretation and Methodology (1.1, 1.2) ]. If the time of ingestion is unknown, or the serum acetaminophen level is not available, cannot be interpreted, or is not available within the hour time interval from acet aminophen ingestio n, Acetadote should be administered immediately if 24 hours or less have elapsed from the reported time of ingestion of an overdose of acetaminophen, regardless of th quantity reported to have been ingested. The aspartate aminotransfera se (AST, SGOT), alanine aminotranferase (ALT, SGPT), bilirubin, prothrombin time, creatinine, blood urea nitrogen (BUN), blood glucose, and electrolytes also should be determined in order to monitor hepatic and renal function and electrolyte and fluid balance. NOTE: The critical ingestion-treatment interval for maximal protection against severe hepatic injury is between ? hours. Efficacy diminishes progressively after hours and treatment initiation between 15 and 24 hours post-ingestion of acetaminophen yields limited fficacy. However, it does not appear to worsen the condition of patients and it should not be withheld, since the reported time of ingestion may not be correct. 1.1 Acetaminophen Assays Interpretation and Methodology Acute Ingestion The acute ingestion of acetam inophen in quantities of 150 mg/kg or greater may result in hepatic toxicity. However, the reported history of the quantity of drug ingested as an overdose is often inaccurate and is not reliable guide to therapy of the overdose. Th erefore, plasma or serum acetaminophen concentrations, determined as early as possible, but no sooner than four hours following an acute overdose, are essential in assessing the potential risk of hepatotoxicity. If an assa for acetaminophen cannot be obtained, it is necessary to assume that the overdose is potentially toxic. Interpretation of cetaminophen Assays 1. When results of the plasma acetaminophen assay are available, refer to the nomogram in Figure to determine if plasma concentration is in the potentially toxic range. Values above the line connecting 200 mcg/mL at hours with 50 mcg/mL at 12 hours (probable line) are associated with probability of hepatic toxicity if an antidote is not administered. 2. If the predetoxification plasma level is above the line connecting 150 mcg/mL at hours with 37.5 mcg/mL at 12 hours (possible line), continue with maintenance doses of acetylcysteine. It is better to err on the safe side and thus this line, defining possible toxicity, is plotted 25% below the line defining probable toxicity. 3. If the predetoxification plasma level is below the line connecting 150 mcg/mL at hours with 37.5 mcg/mL at 12 hours (possible line), there is minimal risk of hepatic toxicity, and acetylcysteine treatment may be discontinued. Estimating Potential for Hepatotoxicity: The following depiction of the Rumack-Ma tthew nomogram has been developed to estimate the probability that plasma levels in relation to intervals post-ingestion will result in hepatotoxicity. Figure 1. Rumack-Matthew Nomogram: Plasma or Serum Acetaminophen Concentration vs. Time Post Acetaminophen Ingestion (Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics. 1975;55:871-876 and Rumack BH, Peterson RC, Kock GG, Amara IA. Acetaminophen overdose. 662 cases with evaluation of oral acetylcysteine treatment. Arch Intern Med. 1981;141:380- 385.)
