Acetylcysteine Solution

Name: Acetylcysteine Solution

How is this medicine (Acetylcysteine Solution) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

Liquid for breathing in:

  • For breathing in only as a liquid (solution) by a special machine (nebulizer) into the lungs.
  • If acetylcysteine solution is used with a face mask, your face may feel sticky after using. Wash your face with water.
  • Do not use if the solution is leaking or has particles.

Oral liquid:

  • Mix with diet soda and drink.
  • Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.
  • If you throw up within 1 hour of taking this medicine, take 1 more dose.

What do I do if I miss a dose?

  • Use a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not use 2 doses at the same time or extra doses.

Warnings

After proper administration of acetylcysteine, an increased volume of liquified bronchial secretions may occur. When cough is inadequate, the open airway must be maintained by mechanical suction if necessary. When there is a mechanical block due to foreign body or local accumulation, the airway should be cleared by endotracheal aspiration, with or without bronchoscopy. Asthmatics under treatment with acetylcysteine should be watched carefully. Most patients with bronchospasm are quickly relieved by the use of a bronchodilator given by nebulization. If bronchospasm progresses, this medication should be discontinued immediately.

Precautions

General

With the administration of acetylcysteine, the patient may initially notice a slight disagreeable odor that is soon noticeable. With a face mask there may be a stickiness on the face after nebulization. This is easily removed by washing with water.

Under certain conditions, a color change may occur in the solution of acetylcysteine in the opened bottle. The light purple color is the result of a chemical reaction which does not significantly affect the safety or mucolytic effectiveness of acetylcysteine.

Continued nebulization of an Acetylcysteine Solution with a dry gas will result in an increased concentration of the drug in the nebulizer because of evaporation of the solvent. Extreme concentration may impede nebulization and efficient delivery of the drug. Dilution of the nebulizing solution with appropriate amounts of Sterile Water for Injection, as a concentration occurs, will obviate this problem.

Drug Interactions

Drug stability and safety of acetylcysteine when mixed with other drugs in a nebulizer have not been established.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Carcinogenicity studies in laboratory animals have not been performed with acetylcysteine alone, nor with acetylcysteine in combination with isoproterenol.

Long-term oral studies of acetylcysteine alone in rats (12 months of treatment followed by 6 months of observation) at doses up to 1,000 mg/kg/day (5.2 times the human mucolytic dose) provided no evidence of oncogenic activity.

Mutagenesis

Published data1 indicate that acetylcysteine is not mutagenic in the Ames test, both with and without metabolic activation.

Impairment of Fertility

A reproductive toxicity test to assess potential impairment of fertility was performed with acetylcysteine (10%) combined with isoproterenol (0.05%) and administered as an aerosol into a chamber of 12.43 cubic meters. The combination was administered for 25, 30, or 35 minutes twice a day for 68 days before mating, to 200 male and 150 female rats; no adverse effects were noted in dams or pups. Females after mating were continued on treatment for the next 42 days.

Reproductive toxicity studies of acetylcysteine in the rat given oral doses of acetylcysteine up to 1,000 mg/kg (5.2 times the human mucolytic dose) have also been reported in the literature1. The only adverse effect observed was a slight non-dose-related reduction in fertility at dose levels of 500 or 1,000 mg/kg/day (2.6 or 5.2 times the human dose) in the Segment 1 study.

Pregnancy: Teratogenic Effects: Pregnancy Category B

In a teratology study of acetylcysteine in the rabbit, oral doses of 500 mg/kg/day (2.6 times the human mucolytic dose) were administered to pregnant does by intubation on days 6 through 16 of gestation. Acetylcysteine was found to be nonteratogenic under the conditions of study.

In the rabbit, two groups (one of 14 and one of 16 pregnant females) were exposed to an aerosol of 10% acetylcysteine and 0.05% isoproterenol hydrochloride for 30 or 35 minutes twice a day from the 6th through the 18th day of pregnancy. No teratogenic effects were observed among the offspring.

Teratology and a perinatal and postnatal toxicity study in rats were performed with a combination of acetylcysteine and isoproterenol administered by the inhalation route. In the rat, two groups of 25 pregnant females each were exposed to the aerosol for 30 and 35 minutes, respectively, twice a day from the 6th through the 15th day of gestation. No teratogenic effects were observed among the offspring.

In the pregnant rat (30 rats per group), twice-daily exposure to an aerosol of acetylcysteine and isoproterenol for 30 or 35 minutes from the 15th day of gestation through the 21st day postpartum was without adverse effect on dams or newborns.

Reproduction studies of acetylcysteine with isoproterenol have been performed in rats and of acetylcysteine alone in rabbits at doses up to 2.6 times the human dose. These have revealed no evidence of impaired fertility or harm to the fetus due to acetylcysteine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies may not always be predictive of human responses, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when acetylcysteine is administered to a nursing woman.

Adverse reactions

Adverse effects have included stomatitis, nausea, vomiting, fever, rhinorrhea, drowsiness, clamminess, chest tightness, and bronchoconstriction. Clinically overt acetylcysteine induced bronchospasm occurs infrequently and unpredictably even in patients with asthmatic bronchitis or bronchitis complicating bronchial asthma.

Acquired sensitization to acetylcysteine have been reported rarely. Reports of sensitization in patients have not been confirmed by patch testing. Sensitization has been confirmed in several inhalation therapists who reported a history of dermal eruptions after frequent and extended exposure to acetylcysteine.

Reports of irritation to the tracheal and bronchial tracts have been received and although hemoptysis has occurred in patients receiving acetylcysteine such findings are not uncommon in patients with bronchopulmonary disease and a causal relationship has not been established.

CA-2283 (Front)

CA-2283 (Back)

ACETYLCYSTEINE 
Acetylcysteine Solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0409-3307
Route of Administration ORAL, RESPIRATORY (INHALATION) DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ACETYLCYSTEINE (ACETYLCYSTEINE) ACETYLCYSTEINE 100 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
EDETATE DISODIUM 0.25 mg  in 1 mL
SODIUM HYDROXIDE  
HYDROCHLORIC ACID  
Packaging
# Item Code Package Description
1 NDC:0409-3307-03 3 VIAL in 1 CARTON
1 30 mL in 1 VIAL
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA073664 08/30/1994
ACETYLCYSTEINE 
Acetylcysteine Solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0409-3308
Route of Administration ORAL, RESPIRATORY (INHALATION) DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ACETYLCYSTEINE (ACETYLCYSTEINE) ACETYLCYSTEINE 200 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
EDETATE DISODIUM 0.5 mg  in 1 mL
SODIUM HYDROXIDE  
HYDROCHLORIC ACID  
Packaging
# Item Code Package Description
1 NDC:0409-3308-03 3 VIAL in 1 CARTON
1 30 mL in 1 VIAL
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA074037 08/30/1994
Labeler - Hospira, Inc. (141588017)
Revised: 08/2015   Hospira, Inc.

Description

Acetylcysteine is the nonproprietary name for the N-acetyl derivative of the naturally occurring amino acid, L-cysteine. Chemically, it is 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 structural formula of acetylcysteine is:


C5H9NO3 .............. M.W.=163.19

Acetylcysteine Solution (n-acetyl-l-cysteine) , USP is supplied as a sterile unpreserved solution (not for injection) in vials containing a 10% (100 mg/mL) or 20% (200 mg/mL) solution of acetylcysteine as the sodium salt. The inactive ingredients are edetate disodium, sodium hydroxide and Sterile Water for Injection, USP. The pH of the solution ranges from 6.0 to 7.5. It is administered by inhalation or direct instillation for mucolysis, or orally for acetaminophen overdosage.

How supplied

Acetylcysteine Solution, USP (n-acetyl-l-cysteine) , is available in rubber stopped glass vials containing 10 or 30 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.

Acetycysteine is sterile, not for injection and can be used for inhalation (mucolytic agent) or oral administration (acetaminophen antidote). It is available as follows:

10% Acetylcysteine Solution, USP (n-acetyl-l-cysteine) (100 mg acetylcysteine per mL).

NDC 0054-3027-02....................................10 mL vials; carton of 3
NDC 0054-3025-02....................................30 mL vials; carton of 3

20% Acetylcysteine Solution, USP (n-acetyl-l-cysteine) (200 mg acetylcysteine per mL).

NDC 0054-3028-02.....................................10 mL vials; carton of 3
NDC 0054-3026-02.....................................30 mL vials; carton of 3

Store unopened vials at controlled room temperature, 15° to 30°C (59° to 86°F).

Acetylcysteine Solution, USP (n-acetyl-l-cysteine) 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.

REFERENCES

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

2. Amer Rev Resp Dis 1960 82:627-639.

Mfd. by Ben Venue Laboratories, Inc., Bedford, Ohio 44146. Revised March 2007. Mfd. for Boehringer Ingelheim Roxane Laboratories. FDA Rev date: 8/28/2000

Clinical pharmacology

ACETYLCYSTEINE AS A MUCOLYTIC AGENT

The viscosity of pulmonary mucous secretions depends on the concentrations of mucoprotein and, to a lesser extent, deoxyribonucleic acid (DNA). The latter increases with increasing purulence owing to the presence of cellular debris. The mucolytic action of acetylcysteine is related to the sulfhydryl group in the molecule. This group probably "opens" disulfide linkages in mucous thereby lowering the viscosity. The mucolytic activity of acetylcysteine is unaltered by the presence of DNA, and increases with increasing pH. Significant mucolysis occurs between pH 7 and 9.

Acetylcysteine undergoes rapid deacetylation in vivo to yield cysteine or oxidation to yield diacetylcysteine. Occasionally, patients exposed to the inhalation of an acetylcysteine aerosol respond with the development of increased airways obstruction of varying and unpredictable severity. Those patients who are reactors cannot be identified a priori from a random patient population. Even when patients are known to have reacted previously to the inhalation of an acetylcysteine aerosol, they may not react during a subsequent treatment. The converse is also true; patients who have had inhalation treatments of acetylcysteine without incident may still react to a subsequent inhalation with increased airways obstruction. Most patients with bronchospasm are quickly relieved by the use of a bronchodilator given by nebulization. If bronchospasm progresses, the medication should be discontinued immediately.

ACETYLCYSTEINE AS AN ANTIDOTE FOR ACETAMINOPHEN OVERDOSAGE

(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.

Side effects

ACETYLCYSTEINE AS A MUCOLYTIC AGENT

Adverse effects have included stomatitis, nausea, vomiting, fever, rhinorrhea, drowsiness, clamminess, chest tightness and bronchoconstriction. Clinically overt acetylcysteine induced bronchospasm occurs infrequently and unpredictably even in patients with asthmatic bronchitis or bronchitis complicating bronchial asthma.

Acquired sensitization to acetylcysteine has been reported rarely. Reports of sensitization in patients have not been confirmed by patch testing. Sensitization has been confirmed in several inhalation therapists who reported a history of dermal eruptions after frequent and extended exposure to acetylcysteine.

Reports of irritation to the tracheal and bronchial tracts have been received and although hemoptysis has occurred in patients receiving acetylcysteine such findings are not uncommon in patients with bronchopulmonary disease and a causal relationship has not been established.

ACETYLCYSTEINE AS AN ANTIDOTE FOR ACETAMINOPHEN OVERDOSAGE

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.

Read the entire FDA prescribing information for Acetylcysteine Solution (N-acetyl-L-cysteine)

Read More »
(web3)