Acetylcysteine (injection)

Acetylcysteine (injection)
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Deepika Beereddy, MBBS [2]

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Overview

Acetylcysteine (injection) is an antioxidant, respiratory system agent that is FDA approved for the treatment of acetaminophen overdose, adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions in such conditions as chronic bronchopulmonary disease (chronic emphysema, emphysema with bronchitis, chronic asthmatic bronchitis, tuberculosis, bronchiectasis and primary amyloidosis of the lung), acute bronchopulmonary disease (pneumonia, bronchitis, tracheobronchitis), pulmonary complications of cystic fibrosis, tracheostomy care, pulmonary complications associated with surgery, use during anesthesia, post-traumatic chest conditions, atelectasis due to mucous obstruction, diagnostic bronchial studies (bronchograms, bronchospirometry, and bronchial wedge catheterization). Common adverse reactions include rash, urticaria/facial flushing and pruritus, diarrhea, nausea, vomiting.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Acetaminophen overdose

Acetylcysteine Injection is an antidote for acetaminophen overdose indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen. Overdose incidences are divided into two types; Acute Ingestion or Repeated Supratherapeutic Ingestion (RSI). [see Dosage and Administration (2) and Acetaminophen Assays – Interpretation and Methodology -(Acute or Repeated Supratherapeutic Ingestion) (1.1, 1.2)].

On admission for suspected acetaminophen overdose, a serum blood sample should be drawn at least 4 hours after ingestion to determine the acetaminophen level and will serve as a basis for determining the need for treatment with acetylcysteine. If the patient presents after 4 hours post-ingestion, the serum acetaminophen sample should be determined immediately.

Acetylcysteine Injection should be administered within 8 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 4 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 8 hour time interval from acetaminophen ingestion, Acetylcysteine Injection should be administered immediately if 24 hours or less have elapsed from the reported time of ingestion of an overdose of acetaminophen, regardless of the quantity reported to have been ingested.

The aspartate aminotransferase (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 0 to 8 hours. Efficacy diminishes progressively after 8 hours and treatment initiation between 15 and 24 hours post-ingestion of acetaminophen yields limited efficacy. 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 acetaminophen in quantities of 150 mg/kg or greater may result in hepatic toxicity. However, the reported history of the quantity of a drug ingested as an overdose is often inaccurate and is not a reliable guide to therapy of the overdose. Therefore, 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 assay for acetaminophen cannot be obtained, it is necessary to assume that the overdose is potentially toxic.

Interpretation of Acetaminophen Assays

When results of the plasma acetaminophen assay are available, refer to the nomogram in Figure 1 to determine if plasma concentration is in the potentially toxic range. Values above the line connecting 200 mcg/mL at 4 hours with 50 mcg/mL at 12 hours (probable line) are associated with a probability of hepatic toxicity if an antidote is not administered. If the predetoxification plasma level is above the line connecting 150 mcg/mL at 4 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. If the predetoxification plasma level is below the line connecting 150 mcg/mL at 4 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- Matthew nomogram has been developed to estimate the probability that plasma levels in relation to intervals post-ingestion will result in hepatotoxicity.

The Rumack-Matthew nomogram may underestimate the risk for hepatotoxicity in some patients with risk factors such as chronic alcoholism, malnutrition, or CYP2E1 enzyme inducing drugs (e.g., isoniazid).

Figure 1. Michael J Hodgman, Alexander R Garrard, A Review of Acetaminophen Poisoning. Crit Care Clin. 28 (2012) 499-516. Stephen J. Wolf, Kennon Heard, et.al, Clinical Policy: Critical Issues in the Management of Patients Presenting to the Emergency Department with Acetaminophen Overdose. Ann Emerg Med. 2007:50:292-313.

1.2 Acetaminophen Assays Interpretation and Methodology – Repeated Supratherapeutic Ingestion

Repeated Supratherapeutic Ingestion (RSI) is defined as ingestion of acetaminophen at doses higher than those recommended for extended periods of time. The nomogram does not apply to patients with RSI. Treatment is based on the acetaminophen and elevated AST/ALT levels indicative of potential toxicity due to acetaminophen. For specific treatment information regarding the clinical management of repeated supratherapeutic acetaminophen overdose, please contact 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.

Figure 2. Acetylcysteine Injection Treatment Flow Chart

1Acetaminophen levels drawn less than 4 hours post-ingestion may be misleading.

2With an extended-release preparation, an acetaminophen level drawn less than 8 hours post-ingestion may be misleading. Draw a second level at 4 to 6 hours after the initial level. If either falls above the toxicity line, acetylcysteine treatment should be initiated.

3Acetylcysteine may be withheld until acetaminophen assay results are available as long as initiation of treatment is not delayed beyond 8 hours post-ingestion. If more than 8 hours post-ingestion, start acetylcysteine treatment immediately.

• Dosing Information

• The total dose of Acetylcysteine Injection is 300 mg/kg given as 3 separate doses and administered over a total of 21 hours. Please refer to the guidelines below for dose preparation based upon patient weight. The total volume administered should be adjusted for patients less than 40 kg and for those requiring fluid restriction (see Tables 1 and 2).

2.1 Administration Instructions (Three-Bag Method: Loading, Second and Third Dose)

Dosing for Patients who weigh 5 kg to 20 kg (Table 1):

Loading Dose: 150 mg/kg diluted in 3 mL/kg of diluent* administered over 1 hr

Second Dose: 50 mg/kg diluted in 7 mL/kg of diluent* administered over 4 hrs

Third Dose: 100 mg/kg diluted in 14 mL/kg of diluent* administered over 16 hrs

See also Section 2.2 Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction

Dosing for patients who weigh 21 kg to 40 kg (Table 2):

Loading Dose: 150 mg/kg diluted in 100 mL of diluent* administered over 1 hr

Second Dose: 50 mg/kg diluted in 250 mL of diluent* administered over 4 hrs

Third Dose: : 100 mg/kg diluted in 500 mL of diluent* administered over 16 hrs

See also Section 2.2 Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction.

Dosing for patients who weigh 41 kg to 100 kg (Table 3):

Loading Dose: 150 mg/kg diluted in 200 mL of diluent* administered over 1 hr

Second Dose: 50 mg/kg diluted in 500 mL of diluent* administered over 4 hrs

Third Dose: 100 mg/kg diluted in 1,000 mL of diluent administered over 16 hrs

Patients Weighing More Than 100 kg

No specific studies have been conducted to evaluate the use of or necessity of dosing adjustments in patients weighing over 100 kg. Limited information is available regarding the dosing requirements of patients that weigh more than 100 kg. The dose of Acetylcysteine Injection recommended in these patients should be a loading dose of 15,000 mg infused over a period of one hour followed by a first maintenance dose of 5,000 mg over 4 hours and a second maintenance dose of 10,000 mg over 16 hours (Table 3).

Continued Therapy beyond 21 Hours

While there is no clinical trial data to support infusions beyond 21 hours there is literature that supports continued infusion of acetylcysteine in some rare instances. 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 infusion of N-acetylcysteine beyond 21 hours. Acetaminophen levels and ALT/AST & INR should be checked before the end of the 21-hour infusion. If acetaminophen levels are still detectable, or in cases in which the ALT/AST are still increasing or the INR remains elevated, the infusion 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.

2.2 Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction

The total volume 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 clinically needed. If the volume of the infusion is not adjusted, fluid overload can occur, potentially resulting in hyponatremia, seizure and death. [see Dosage and Administration (2)]

As Acetylcysteine Injection is hyperosmolar (2600 mOsmol/L), caution is advised when the diluent volume is decreased as the hyperosmolarity of the solution is increased. See Table 4 below for examples.

Single dose vial, preservative-free, discard unused portion. If vial was previously opened, do not use for intravenous administration.

Stability studies indicate that the diluted solution is stable for 24 hours at controlled room temperature.

Note: The color of Acetylcysteine Injection 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.

2.3 Renal Impairment

No data are available to determine if a dose adjustment in patients with moderate or severe renal impairment is required.

2.4 Hepatic Impairment

Although there was a threefold increase in acetylcysteine plasma concentrations in patients with hepatic cirrhosis, no data are available to determine if a dose adjustment in these patients is required. The published medical literature does not indicate that the dose of acetylcysteine in patients with hepatic impairment should be reduced.

DOSAGE FORMS & STRENGTHS

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

Administration of anesthesia for procedure

• Dosing Information

• Dosage

Atelectasis, Due to mucous obstruction

• Dosing Information

• Dosage

Bronchopulmonary disease, acute

• Dosing Information

• Dosage

Complication of surgical procedure - Respiratory complication

Cystic fibrosis, Pulmonary complications; Adjunct

Diagnostic procedure on lower respiratory tract

Disease of respiratory system, chronic

Tracheostomy care

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Acetylcysteine (injection) in adult patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Acetylcysteine (injection) in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Acetaminophen overdose

• Dosing Information

• Dosage

Administration of anesthesia for procedure

Atelectasis, Due to mucous obstruction

Bronchopulmonary disease, acute

Complication of surgical procedure - Respiratory complication

Cystic fibrosis, Pulmonary complications; Adjunct

Diagnostic procedure on lower respiratory tract

Disease of respiratory system, chronic

Tracheostomy care

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Acetylcysteine (injection) in pediatric patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Acetylcysteine (injection) in pediatric patients.

Contraindications

• Condition1

Warnings

• Description

Precautions

• Description

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Acetylcysteine (injection) in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Acetylcysteine (injection) in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Drug Interactions

• Drug

• Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Acetylcysteine (injection) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Acetylcysteine (injection) during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Acetylcysteine (injection) with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Acetylcysteine (injection) with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Acetylcysteine (injection) with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Acetylcysteine (injection) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Acetylcysteine (injection) with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Acetylcysteine (injection) in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Acetylcysteine (injection) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Acetylcysteine (injection) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Acetylcysteine (injection) in patients who are immunocompromised.

Administration and Monitoring

Administration

The total dose of Acetylcysteine Injection is 300 mg/kg given as 3 separate doses and administered over a total of 21 hours. Please refer to the guidelines below for dose preparation based upon patient weight. The total volume administered should be adjusted for patients less than 40 kg and for those requiring fluid restriction (see Tables 1 and 2).

2.1 Administration Instructions (Three-Bag Method: Loading, Second and Third Dose)

Dosing for Patients who weigh 5 kg to 20 kg (Table 1):

Loading Dose: 150 mg/kg diluted in 3 mL/kg of diluent* administered over 1 hr

Second Dose: 50 mg/kg diluted in 7 mL/kg of diluent* administered over 4 hrs

Third Dose: 100 mg/kg diluted in 14 mL/kg of diluent* administered over 16 hrs

See also Section 2.2 Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction

Dosing for patients who weigh 21 kg to 40 kg (Table 2):

Loading Dose: 150 mg/kg diluted in 100 mL of diluent* administered over 1 hr

Second Dose: 50 mg/kg diluted in 250 mL of diluent* administered over 4 hrs

Third Dose: : 100 mg/kg diluted in 500 mL of diluent* administered over 16 hrs

See also Section 2.2 Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction.

Dosing for patients who weigh 41 kg to 100 kg (Table 3):

Loading Dose: 150 mg/kg diluted in 200 mL of diluent* administered over 1 hr

Second Dose: 50 mg/kg diluted in 500 mL of diluent* administered over 4 hrs

Third Dose: 100 mg/kg diluted in 1,000 mL of diluent administered over 16 hrs

Patients Weighing More Than 100 kg

No specific studies have been conducted to evaluate the use of or necessity of dosing adjustments in patients weighing over 100 kg. Limited information is available regarding the dosing requirements of patients that weigh more than 100 kg. The dose of Acetylcysteine Injection recommended in these patients should be a loading dose of 15,000 mg infused over a period of one hour followed by a first maintenance dose of 5,000 mg over 4 hours and a second maintenance dose of 10,000 mg over 16 hours (Table 3).

Continued Therapy beyond 21 Hours

While there is no clinical trial data to support infusions beyond 21 hours there is literature that supports continued infusion of acetylcysteine in some rare instances. 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 infusion of N-acetylcysteine beyond 21 hours. Acetaminophen levels and ALT/AST & INR should be checked before the end of the 21-hour infusion. If acetaminophen levels are still detectable, or in cases in which the ALT/AST are still increasing or the INR remains elevated, the infusion 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.

2.2 Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction

The total volume 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 clinically needed. If the volume of the infusion is not adjusted, fluid overload can occur, potentially resulting in hyponatremia, seizure and death. [see Dosage and Administration (2)]

As Acetylcysteine Injection is hyperosmolar (2600 mOsmol/L), caution is advised when the diluent volume is decreased as the hyperosmolarity of the solution is increased. See Table 4 below for examples.

Single dose vial, preservative-free, discard unused portion. If vial was previously opened, do not use for intravenous administration.

Stability studies indicate that the diluted solution is stable for 24 hours at controlled room temperature.

Note: The color of Acetylcysteine Injection 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.

2.3 Renal Impairment

No data are available to determine if a dose adjustment in patients with moderate or severe renal impairment is required.

2.4 Hepatic Impairment

Although there was a threefold increase in acetylcysteine plasma concentrations in patients with hepatic cirrhosis, no data are available to determine if a dose adjustment in these patients is required. The published medical literature does not indicate that the dose of acetylcysteine in patients with hepatic impairment should be reduced.

DOSAGE FORMS & STRENGTHS

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

Monitoring

There is limited information regarding Monitoring of Acetylcysteine (injection) in the drug label.

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Acetylcysteine (injection) in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Description

Management

• Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Acetylcysteine (injection) in the drug label.

Pharmacology

There is limited information regarding Acetylcysteine (injection) Pharmacology in the drug label.

Mechanism of Action

Structure

File:Acetylcysteine (injection)01.png

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Acetylcysteine (injection) in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Acetylcysteine (injection) in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Acetylcysteine (injection) in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Acetylcysteine (injection) in the drug label.

How Supplied

Storage

There is limited information regarding Acetylcysteine (injection) Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Acetylcysteine (injection) in the drug label.

Precautions with Alcohol

• Alcohol-Acetylcysteine (injection) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• ®

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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