DOSAGE AND ADMINISTRATION
ACETYLCYSTEINE AS A MUCOLYTIC AGENT
Acetylcysteine Solution, USP (n-acetyl-l-cysteine) is available in rubber stoppered glass vials containing
10 mL or 30 mL. The 20% solution may be diluted to a lesser concentration with
either Sodium Chloride Injection, Sodium Chloride for Inhalation, Sterile Water
for Injection, or Sterile Water for Inhalation. The 10% solution may be used
Acetylcysteine does not contain an antimicrobial agent, and care must be taken
to minimize contamination of the sterile solution. If only a portion of the
solution in a vial is used, store the remainder in a refrigerator and use for
inhalation only within 96 hours.
Nebulization - Face Mask, Mouthpiece, Tracheostomy: When nebulized
into a face mask, mouthpiece, or tracheostomy, 1 to 10 mL of the 20% solution
or 2 to 20 mL of the 10% solution may be given every 2 to 6 hours; the recommended
dose for most patients is 3 to 5 mL of the 20% solution or 6 to 10 mL of the
10% solution three to four times a day.
Nebulization - Tent, Croupette: In special circumstances it may be necessary
to nebulize into a tent or Croupette, and this method of use must be individualized
to take into account the available equipment and the patient's particular needs.
This form of administration requires very large volumes of the solution, occasionally
as much as 300 mL during a single treatment period.
If a tent or Croupette must be used, the recommended dose is the volume of
acetylcysteine (using 10 or 20%) that will maintain a very heavy mist in the
tent or Croupette for the desired period. Administration for intermittent or
continuous prolonged periods, including overnight, may be desirable.
Direct Instillation: When used by direct instillation, 1 to 2 mL of
a 10% to 20% solution may be given as often as every hour.
When used for the routine nursing care of patients with tracheostomy, 1 to
2 mL of a 10% to 20% solution may be given every 1 to 4 hours by instillation
into the tracheostomy.
Acetylcysteine may be introduced directly into a particular segment of the
bronchopulmonary tree by inserting (under local anesthesia and direct vision)
a small plastic catheter into the trachea. Two to 5 mL of the 20% solution may
then be instilled by means of a syringe connected to the catheter.
Acetylcysteine may also be given through a percutaneous intratracheal catheter.
One to 2 mL of the 20% or 2 to 4 mL of the 10% solution every 1 to 4 hours may
then be given by a syringe attached to the catheter.
Diagnostic Bronchograms: For diagnostic bronchial studies, 2 or 3 administrations
of 1 to 2 mL of the 20% solution or 2 to 4 mL of the 10% solution should be
given by nebulization or by instillation intratracheally, prior to the procedure.
Administration of Aerosol
Materials: Acetylcysteine solution (n-acetyl-l-cysteine) may be administered using conventional
nebulizers made of plastic or glass. Certain materials used in nebulization
equipment react with acetylcysteine. The most reactive of these are certain
metals (notably iron and copper) and rubber. Where materials may come into contact
with acetylcysteine solution (n-acetyl-l-cysteine) , parts made of the following acceptable materials
should be used: glass, plastic, aluminum, anodized aluminum, chromed metal,
tantalum, sterling silver, or stainless steel. Silver may become tarnished after
exposure, but this is not harmful to the drug action or to the patient.
Nebulizing Gases: Compressed tank gas (air) or an air compressor should
be used to provide pressure for nebulizing the solution. Oxygen may also be
used but should be used with usual precautions in patients with severe respiratory
disease and CO2 retention.
Apparatus: Acetylcysteine solution (n-acetyl-l-cysteine) is usually administered as fine nebulae
and the nebulizer used should be capable of providing optimal quantities of
a suitable range of particle sizes.
Commercially available nebulizers will produce nebulae of acetylcysteine satisfactory
for retention in the respiratory tract. Most of the nebulizers tested will supply
a high proportion of the drug solution as particles of less than 10 microns
in diameter. Mitchell2 has shown that particles less than 10 microns should
be retained in the respiratory tract satisfactorily.
Various intermittent positive pressure breathing devices nebulized acetylcysteine
with a satisfactory efficiency including: No:40 Da Vilbiss (The Da Vilbiss Co.,
Somerset, PA) and the Bennett Twin-Jet Nebulizer (Puritan Bennett Corp., Oak
at 13th, Kansas City, MO).
The nebulized solution may be inhaled directly from the nebulizer. Nebulizers may also be attached to plastic face masks or plastic mouthpieces. Suitable nebulizers may also be fitted for use with the various intermittent positive pressure breathing (IPPB) machines. The nebulizing equipment should be cleaned immediately after use because the residues may clog the smaller orifices or corrode metal parts.
Hand bulbs are not recommended for routine use for nebulizing acetylcysteine because their output is generally too small. Also, some hand-operated nebulizers deliver particles that are larger than optimum for inhalation therapy.
Acetylcysteine solution (n-acetyl-l-cysteine) should not be placed directly into the chamber of
a heated (hot pot) nebulizer. A heated nebulizer may be part of the nebulization
assembly to provide a warm saturated atmosphere if the acetylcysteine aerosol
is introduced by means of a separate unheated nebulizer. Usual precautions for
administration of warm saturated nebulae should be observed.
The nebulized solution may be breathed directly from the nebulizer. Nebulizers
may also be attached to plastic face masks, plastic face tents, plastic mouthpieces,
conventional plastic oxygen tents, or head tents. Suitable nebulizers may also
be fitted for use with the various intermittent positive pressure breathing
The nebulizing equipment should be cleaned immediately after use, otherwise
the residues may occlude the fine orifices or corrode metal parts.
Prolonged Nebulization: When three-fourths of the initial volume of
acetylcysteine solution (n-acetyl-l-cysteine) has been nebulized, a quantity of Sterile Water for
Injection, USP (approximately equal to the volume of solution remaining) should
be added to the nebulizer. This obviates any concentration of the agent in the
residual solvent remaining after prolonged nebulization.
Compatibility: The physical and chemical compatibility of acetylcysteine
solutions with certain other drugs that might be concomitantly administered
by nebulization, direct instillation, or topical application, has been studied.
Acetylcysteine should not be mixed with certain antibiotics. For example, the
antibiotics tetracycline hydrochloride, oxytetracycline hydrochloride and erythromycin
lactobionate were found to be incompatible when mixed in the same solution.
These agents may be administered from separate solutions if administration of
these agents is desirable.
The supplying of these data should not be interpreted as a recommendation for
combining acetylcysteine with other drugs. The table is not presented as positive
assurance that no incompatibility will be present, since these data are based
only on short-term compatibility studies done in the Mead Johnson Research Center.mManufacturers
may change their formulations, and this could alter compatibilities. These data
are intended to serve only as a guide for predicting compounding problems.
If it is deemed advisable to prepare an admixture, it should be administered
as soon as possible after preparation. Do not store unused mixtures.
ACETYLCYSTEINE AS AN ANTIDOTE FOR ACETAMINOPHEN OVERDOSAGE
Regardless of the quantity of acetaminophen reported to have been ingested, administer acetylcysteine 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 (n-acetyl-l-cysteine) . 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 quantities 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
vitro and may do so in patients and thereby may reduce its effectiveness.
Draw blood for predetoxificaton acetaminophen plasma assay and for baseline
SGOT, SGPT, bilirubin, prothrombin time, creatinine, BUN, blood sugar and
Administer the loading dose of acetylcysteine, 140 mg per kg of body weight.
(Prepare acetylcysteine for oral administration as described in the specific
Dosage Guide and Preparation table.)
Determine the subsequent action based on predetoxification plasma acetaminophen
information. Choose ONE of the following four courses of therapy.
Predetoxification plasma acetaminophen level is clearly in toxic range
(See Acetaminophen Assays - Interpolation 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.
Predetoxification acetominophen level could not be obtained:
Proceed as in A.
Predetoxification acetominophen level is clearly in the nontoxic range
(beneath the dashed line on the nomogram) and you know that acetominophen
overdose occurred at least 4 hours before the predetoxification acetaminophen
Discontinue administration of acetylcysteine.
Predetoxification acetominophen level was in the nontoxic range, but
time of ingestion was unknown or less than 4 hours.
Because the level of acetaminophen at the time of the 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 wether
or not the full 17-dose detoxification treatment is necessary.
If the patient vomits any oral dose within 1 hour of administration, repeat
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 Solution (n-acetyl-l-cysteine) 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 SOLUTION (n-acetyl-l-cysteine) IS NOT APPROVED
FOR PARENTERAL INJECTION.
Acetaminophen Assays - Interpretation and Methodology: 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
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 below to determine if plasma concentration is in the potentially
toxic range. Values above the solid line connecting 200 mcg/mL at 4 hours
with 50 mcg/mL at 12 hours are associated with a possibility of hepatic toxicity
if an antidote is not administered. (Do not wait for assay results to begin
If the predetoxification plasma level is above the broken line, continue
with maintenance doses of acetylcysteine. It is better to err on the safe
side and thus the broken line is placed 25% below the solid line which defines
If the predetoxification plasma level is below the broken line described
above, there is minimal risk of hepatic toxicity and acetylcysteine treatment
can be discontinued.
Acetaminophen Assay Methodology: Assay procedures most suitable for
determining acetaminophen concentrations utilize high pressure liquid chromatography
(HPLC) or gas liquid chromatography (GLC). The assay should measure only parent
acetaminophen and not conjugated. The assay procedures listed below fulfill
Selected Techniques (noninclusive):
1. Blair D and Rumack BH, Clin Chem 1977, 23(4):743-745 (April).
2. Howie D, Andriaenssens PI and Prescott LF, J Pharm Pharmacol 1977, 29(4):235-237
3. Prescott LF, J Pharm Pharmacol 1971, 23(10):807-808 (October).
4. Glynn JP and Kendal SE, Lancet 1975,1 (May 17):1147-1148.
Supportive Treatment of Acetaminophen Overdosage:
Maintain fluid and electrolyte balance based on clinical evaluation of
state of hydration and serum electrolytes.
Treat as necessary for hypoglycemia.
Administer vitamin K1 if prothrombin time ratio exceeds 1.5
or fresh frozen plasma if the prothrombin time ratio exceeds 3.0.
Diuretics and forced diuresis should be avoided.
Dosage Guide and Preparation
Doses in relation to body weight are:
Loading Dose of Acetylcysteine* Solution
| Body Weight
|| grams Acetylcysteine
|| mL of 20% Acetylcysteine Solution
|| mL of Diluent
|| Total mL of 5% Solution
| 90- 99
| 80- 89
| 70- 79
| 60- 69
| 50- 59
| 40- 49
| 30- 39
|| 66- 86
| 20- 29
|| 44- 64
| Maintenance Dose*
| 90- 99
| 80- 89
| 70- 79
| 60- 69
| 50- 59
| 40- 49
| 30- 39
|| 66- 86
| 20- 29
|| 44- 64
| *If patient weighs less than 20 kg (usually patients younger
than 6 years), calculate the dose of acetylcysteine. Each mL of 20% acetylcysteine
solution contains 200 mg of acetylcysteine. The loading dose is 140 mg per
kilogram of body weight. The maintenance dose is 70 mg/kg. Three (3) mL
of diluent are added to each mL of 20% acetylcysteine solution. Do not decrease
the proportion of diluent.
Estimating Potential for Hepatotoxicity
The following nomogram has been developed to estimate the probability that plasma levels in relation to intervals post-ingestion will result in hepatotoxicity.
Plasma or Serum Acetaminophen Concentration vs. Time Post-Acetaminophen
Adapted from Rumack and Mathews, Pediatrics 1975; 55:871-876.
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
Acetycysteine is sterile, not for injection and can be used for inhalation
(mucolytic agent) or oral administration (acetaminophen antidote). It is available
10% Acetylcysteine Solution, USP (n-acetyl-l-cysteine) (100 mg acetylcysteine per mL).
NDC 0054-3027-02....................................10 mL vials; carton
NDC 0054-3025-02....................................30 mL vials; carton
20% Acetylcysteine Solution, USP (n-acetyl-l-cysteine) (200 mg acetylcysteine per mL).
NDC 0054-3028-02.....................................10 mL vials; carton
NDC 0054-3026-02.....................................30 mL vials; carton
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.
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: