PRINCIPAL DISPLAY PANEL - 200 mg/mL Vial Carton

NDC 42494-436-25
Rx Only

Acetylcysteine Solution, USP

20% (200 mg/mL)

For Inhalation (Mucolytic Agent) or Oral Administration (Acetaminophen Antidote)

NOT FOR INJECTION

PRESERVATIVE FREE

25 x 4 mL Vials

INDICATIONS AND USAGE

Acetylcysteine, administered orally, is indicated as an antidote to prevent or lessen hepatic injury which may occur following the ingestion of a potentially hepatotoxic quantity of acetaminophen.

It is essential to initiate treatment as soon as possible after the overdose and, in any case, within 24 hours of ingestion.

CONTRAINDICATIONS

There are no contraindications to oral administration of acetylcysteine in the treatment of acetaminophen overdose.

ADVERSE REACTIONS

Oral administration of acetylcysteine, especially in the large doses needed to treat acetaminophen overdose, may result in nausea, vomiting and other gastrointestinal symptoms. Rash with or without mild fever has been observed rarely.

DESCRIPTION

Acetylcysteine solution is for inhalation (mucolytic agent) or oral administration (acetaminophen antidote), available as a sterile, unpreserved solutions (not for injection). The solutions contain 20% (Acetylcysteine Solution 20%) or 10% (Acetylcysteine Solution 10%) acetylcysteine, with disodium edetate in water for injection. Sodium hydroxide and/or hydrochloric acid is added to adjust to pH (range 6.0 - 7.5). Acetylcysteine is the N-acetyl derivative of the naturally-occurring amino acid, L-cysteine. The compound is a white crystalline powder with the molecular formula C5H9NO3S, a molecular weight of 163.2, and chemical name of N-acetyl-L-cysteine. Acetylcysteine has the following structural formula:

This product contains the following inactive ingredients: edetate disodium, sodium hydroxide and water for injection.

Rx only

Manufactured for:
Cameron Pharmaceuticals
Louisville, Kentucky 40245, USA
Made in China

Revised April 2025

SG250500

CLINICAL PHARMACOLOGY

(Antidotal) Acetaminophen is rapidly absorbed from the upper gastrointestinal tract with peak plasma levels occurring between 30 and 60 minutes after therapeutic doses and usually within 4 hours following an overdose. The parent compound, which is nontoxic, is extensively metabolized in the liver to form principally the sulfate and glucuronide conjugates which are also nontoxic and are rapidly excreted in the urine. A small fraction of an ingested dose is metabolized in the liver by the cytochrome P-450 mixed function oxidase enzyme system to form a reactive, potentially toxic, intermediate metabolite which preferentially conjugates with hepatic glutathione to form the nontoxic cysteine and mercapturic acid derivatives which are then excreted by the kidney. Therapeutic doses of acetaminophen do not saturate the glucuronide and sulfate conjugation pathways and do not result in the formation of sufficient reactive metabolite to deplete glutathione stores. However, following ingestion of a large overdose (150 mg/kg or greater) the glucuronide and sulfate conjugation pathways are saturated resulting in a larger fraction of the drug being metabolized via the P-450 pathway. The increased formation of reactive metabolite may deplete the hepatic stores of glutathione with subsequent binding of the metabolite to protein molecules within the hepatocyte resulting in cellular necrosis.

Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose. Its effectiveness depends on early oral administration, with benefit seen principally in patients treated within 16 hours of the overdose. 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.

REFERENCES

 Bonanomi L, Gazzaniga A. Toxicological, pharmacokinetic and metabolic studies on acetylcysteine. Eur J Respir Dis 1981; 61 (suppl III): 45-51.

2.

 Am Rev Respir Dis 1960; 82:627-639.

WARNINGS

Generalized urticaria has been observed rarely in patients receiving oral acetylcysteine for acetaminophen overdose. If this occurs or other allergic symptoms appear, treatment with acetylcysteine should be discontinued unless it is deemed essential and the allergic symptoms can be otherwise controlled.

If encephalopathy due to hepatic failure becomes evident, acetylcysteine treatment should be discontinued to avoid further administration of nitrogenous substances. There are no data indicating that acetylcysteine influences hepatic failure, but this remains a theoretical possibility.

DOSAGE AND ADMINISTRATION

General

Regardless of the quantity of acetaminophen reported to have been ingested, administer acetylcysteine solution immediately if 24 hours or less have elapsed from the reported time of ingestion of an overdose of acetaminophen. Do not await results of assays for acetaminophen level before initiating treatment with acetylcysteine solution. The following procedures are recommended:

 The stomach should be emptied promptly by lavage or by inducing emesis with syrup of ipecac. Syrup of ipecac should be given in a dose of 15 mL for children up to age 12 and 30 mL for adolescents and adults followed immediately by drinking copious amounts of water. The dose should be repeated if emesis does not occur in 20 minutes.

 In the case of a mixed drug overdose activated charcoal may be indicated. However, if activated charcoal has been administered, lavage before administering acetylcysteine treatment. Activated charcoal adsorbs acetylcysteine in vivo and may do so in patients and thereby may reduce its effectiveness.

 Draw blood for predetoxification acetaminophen plasma assay and baseline SGOT, SGPT, bilirubin, prothrombin time, creatinine, BUN, blood sugar and electrolytes.

 Administer the loading dose of acetylcysteine, 140 mg per kg of body weight. (Prepare acetylcysteine for oral administration as described in the Dosage Guide and Preparation table).

 Determine subsequent action based on predetoxification plasma acetaminophen information. Choose**ONE** of the following four courses of therapy.

A.

 Predetoxification plasma acetaminophen level is clearly in the toxic range (See**Acetaminophen Assays - Interpretation and Methodology** below):  

Administer a first maintenance dose (70 mg/kg acetylcysteine) 4 hours after the loading dose. The maintenance dose is then repeated at 4-hour intervals for a total of 17 doses.
Monitor hepatic and renal function and electrolytes throughout the detoxification process.

B.

 Predetoxification acetaminophen level could not be obtained:  

Proceed as in A.

C.

 Predetoxification acetaminophen level is clearly in the non-toxic range (beneath the dashed line on the nomogram) and you know that acetaminophen overdose occurred at least 4 hours before the predetoxification acetaminophen plasma assays:  

Discontinue administration of acetylcysteine.

D.

Predetoxification acetaminophen level was in the non-toxic range, but time of ingestion was unknown or less than 4 hours.  

Because the level of acetaminophen at the time of predetoxification assay may not be a peak value (peak may not be achieved before 4 hours post-ingestion), obtain a second plasma level in order to decide whether or not the full 17-dose detoxification treatment is necessary.

 If the patient vomits any oral dose within 1 hour of administration, repeat that dose.

 In the occasional instances where the patient is persistently unable to retain the orally administered acetylcysteine, the antidote may be administered by duodenal intubation.

 Repeat SGOT, SGPT, bilirubin, prothrombin time, creatinine, BUN, blood sugar and electrolytes daily if the acetaminophen plasma level is in the potentially toxic range as discussed below.

Preparation of Acetylcysteine for Oral Administration

Oral administration requires dilution of the 20% solution with diet cola or other diet soft drinks, to a final concentration of 5% (see Dosage Guide and Preparation table). If administered via gastric tube or Miller-Abbott tube, water may be used as the diluent. The dilutions should be freshly prepared and utilized within one hour. Remaining undiluted solutions in opened vials can be stored in the refrigerator up to 96 hours.ACETYLCYSTEINE IS NOT APPROVED FOR PARENTERAL INJECTION.

PRECAUTIONS

Occasionally severe and persistent vomiting occurs as a symptom of acute acetaminophen overdose. Treatment with oral acetylcysteine may aggravate the vomiting. Patients at risk of gastric hemorrhage (eg, esophageal varices, peptic ulcers, etc.) should be evaluated concerning the risk of upper gastrointestinal hemorrhage versus the risk of developing hepatic toxicity, and treatment with acetylcysteine given accordingly.

Dilution of the acetylcysteine (seePreparation of Acetylcysteine Solution for Oral Administration) minimizes the propensity of oral acetylcysteine to aggravate vomiting.

HOW SUPPLIED

Acetylcysteine solution is supplied as a clear, colorless liquid in a clear glass vial with an elastomeric stopper and an aluminum seal with a plastic flip-off dust cover containing 4 to 10 mL. The 20% solution may be diluted to a lesser concentration with either Sodium Chloride for Injection, Sodium Chloride for Inhalation, Sterile Water for Injection, or Sterile Water for Inhalation. The 10% solution may be used undiluted.

Acetylcysteine solution is sterile and can be used for inhalation (mucolytic agent) or oral administration (acetaminophen antidote).

Acetylcysteine solution is not for parenteral injection. It is available as:

Acetylcysteine solution 10% (100 mg acetylcysteine per mL). Sterile, not for injection.

NDC 42494-435-25	Cartons of twenty-five 4 mL vials
NDC 42494-439-03	Cartons of three 10 mL vials, 1 plastic dropper

Acetylcysteine solution 20% (200 mg acetylcysteine per mL). Sterile, not for injection.

NDC 42494-436-25	Cartons of twenty-five 4 mL vials
NDC 42494-440-03	Cartons of three 10 mL vials, 1 plastic dropper

STORAGE

Store unopened vials at 20 ° - 25 °C (68 ° - 77 °F); excursions permitted to 15 °- 30 °C (59 ° – 86 °F) (see USP Controlled Room Temperature).

Acetylcysteine solution does not contain an antimicrobial agent, and care must be taken to minimize contamination of the sterile solution. Dilutions of acetylcysteine should be used freshly prepared and utilized within one hour. If only a portion of the solution in a vial is used, store the remaining undiluted portion in a refrigerator and use within 96 hours. A change in color may occur after opening. This does change the efficacy of the drug.