Acetylcysteine Injection

Name: Acetylcysteine Injection

Uses of Acetylcysteine Injection

  • It is used to treat acetaminophen overdose.
  • It may be given to you for other reasons. Talk with the doctor.

What are some other side effects of Acetylcysteine Injection?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Upset stomach or throwing up.
  • Flushing.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Dosage Forms and Strengths

Injection: 200 mg/mL (6 grams of acetylcysteine in 30 mL) in a single-dose vial.

Warnings and Precautions

Hypersensitivity Reactions

Serious acute hypersensitivity reactions during acetylcysteine administration including rash, hypotension, wheezing, and/or shortness of breath, have been observed in patients receiving intravenous acetylcysteine for acetaminophen overdose and occurred soon after initiation of the infusion [see Adverse Reactions (6.1)]. If a severe hypersensitivity reaction occurs, immediately stop the infusion of acetylcysteine and initiate appropriate treatment.

One patient with asthma developed bronchospasm and died after intravenous administration of acetylcysteine. Acetylcysteine should be used with caution in patients with asthma, or where there is a history of bronchospasm. Patients with asthma should be closely monitored during initiation of acetylcysteine therapy and throughout acetylcysteine therapy.

Acute flushing and erythema of the skin may occur in patients receiving acetylcysteine intravenously. These reactions usually occur 30 to 60 minutes after initiating the infusion and often resolve spontaneously despite continued infusion of acetylcysteine. If a reaction to acetylcysteine involves more than simply flushing and erythema of the skin, it should be treated as a hypersensitivity reaction.

Management of less severe hypersensitivity reactions should be based upon the severity of the reaction and include temporary interruption of the infusion and/or administration of antihistaminic drugs. The acetylcysteine infusion may be carefully restarted after treatment of the hypersensitivity symptoms has been initiated; however, if the hypersensitivity reaction returns upon re-initiation of treatment or increases in severity, acetylcysteine should be discontinued and alternative patient management should be considered.

Fluid Overload

The total volume of acetylcysteine administered should be adjusted for patients less than 40 kg and for those requiring fluid restriction. To avoid fluid overload, the volume of diluent should be reduced as needed [see Dosage and Administration (2)]. If volume is not adjusted fluid overload can occur, potentially resulting in hyponatremia, seizure and death.

Intravenous administration of acetylcysteine can cause fluid overload, potentially resulting in hyponatremia, seizure and death. To avoid fluid overload, use the recommended dilution shown in Tables 2, 3 and 4 [see Dosage and Administration (2.4)].

Acetylcysteine Injection Description

Acetylcysteine Injection is an intravenous antidote for the treatment of acetaminophen overdose. Acetylcysteine is the nonproprietary name for the N-acetyl derivative of the naturally occurring amino acid, L-cysteine (N-acetyl-L-cysteine). The compound is a white crystalline powder, which melts in the range of 104° to 110°C and has a very slight odor. The molecular formula of the compound is C5H9NO3S, and its molecular weight is 163.2. Acetylcysteine has the following structural formula:

Acetylcysteine Injection is supplied as a sterile solution in vials containing 20% w/v (200 mg/mL) acetylcysteine. The pH of the solution ranges from 6.0 to 7.5. Acetylcysteine Injection contains the following inactive ingredients: 0.5 mg/mL disodium edetate, sodium hydroxide (used for pH adjustment), and Sterile Water for Injection, USP.

Clinical Studies

Loading Dose/Infusion Rate Study

A randomized, open-label, multi-center clinical study was conducted in Australia in patients with acetaminophen poisoning to compare the rates of hypersensitivity reactions between two rates of infusion for the intravenous acetylcysteine loading dose. One hundred nine subjects were randomized to a 15-minute infusion rate and seventy-one subjects were randomized to a 60-minute infusion rate. The loading dose was 150 mg/kg followed by a maintenance dose of 50 mg/kg over 4 hours and then 100 mg/kg over 16 hours. Of the 180 patients, 27% were male and 73% were female. Ages ranged from 15 to 83 years, with the mean age being 30 years (±13.0).

A subgroup of 58 subjects (33 in the 15-minute infusion group; 25 in the 60-minute infusion group) was treated within 8 hours of acetaminophen ingestion. No hepatotoxicity occurred within this subgroup; however, with 95% confidence, the true hepatotoxicity rates could range from 0% to 9% for the 15-minute infusion group and from 0% to 12% for the 60-minute infusion group.

Observational Study

An open-label, observational database contained information on 1,749 patients who sought treatment for acetaminophen overdose over a 16-year period. Of the 1,749 patients, 65% were female, 34% were male and less than 1% was transgender. Ages ranged from 2 months to 96 years, with 72% of the patients falling in the 16- to 40-year-old age bracket. A total of 399 patients received acetylcysteine treatment. A post-hoc analysis identified 56 patients who (1) were at high or probable risk for hepatotoxicity (APAP greater than 150 mg/L at the four hours line according to the Australian nomogram) and (2) had a liver function test. Of the 53 patients who were treated with intravenous acetylcysteine (300 mg/ kg intravenous acetylcysteine administered over 20 to 21 hours) within 8 hours, two (4%) developed hepatotoxicity (AST or ALT greater than 1,000 U/L). Twenty-one of 48 (44%) patients treated with acetylcysteine after 15 hours developed hepatotoxicity. The actual number of hepatotoxicity outcomes may be higher than what is reported here. For patients with multiple admissions for acetaminophen overdose, only the first overdose treated with intravenous acetylcysteine was examined. Hepatotoxicity may have occurred in subsequent admissions.

Evaluable data were available from a total of 148 pediatric patients (less than 16 years of age) who were admitted for poisoning following ingestion of acetaminophen, of whom 23 were treated with intravenous acetylcysteine. There were no deaths of pediatric patients. None of the pediatric patients receiving intravenous acetylcysteine developed hepatotoxicity while two patients not receiving intravenous acetylcysteine developed hepatotoxicity. The number of pediatric patients is too small to provide a statistically significant finding of efficacy; however the results appear to be consistent to those observed for adults.

Description

Acetylcysteine injection is an intravenous antidote for the treatment of acetaminophen overdose. Acetylcysteine is the nonproprietary name for the N-acetyl derivative of the naturally occurring amino acid, L-cysteine (N-acetyl-L-cysteine). The compound is a white crystalline powder, which melts in the range of 104° to 110°C and has a very slight odor. The molecular formula of the compound is C5H9NO3S, and its molecular weight is 163.2. Acetylcysteine has the following structural formula:

Acetadote is supplied as a sterile solution in vials containing 20% w/v (200 mg/mL) acetylcysteine. The pH of the solution ranges from 6.0 to 7.5. Acetadote contains the following inactive ingredients: sodium hydroxide (used for pH adjustment), and Sterile Water for Injection, USP.

How supplied

Dosage Forms And Strengths

Each single dose vial contains 6g/30mL (200 mg/mL) of Acetadote (acetylcysteine) Injection. Acetadote is sterile and can be used for intravenous administration.

Storage And Handling

Acetadote (acetylcysteine) Injection is available as a 20% solution (200mg/mL) in 30 mL single dose glass vials. Each single dose vial contains 6g/30mL (200 mg/mL) of Acetadote Injection. Acetadote is sterile and can be used for intravenous administration. It is available as follows:

30 mL vials, carton of 4 (NDC 66220-207-30)

Do not use previously opened vials for intravenous administration.

Note: The color of Acetadote may turn from essentially colorless to a slight pink or purple once the stopper is punctured. The color change does not affect the quality of the product.

The stopper in the Acetadote vial is formulated with a synthetic base-polymer and does not contain Natural Rubber Latex, Dry Natural Rubber, or blends of Natural Rubber.

Storage

Store unopened vials at controlled room temperature, 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

*Sections or subsections omitted from the Full Prescribing Information are not listed.

Manufactured for: Cumberland Pharmaceuticals Inc., Nashville, TN 37203. Revised: June 2013

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