Acetadote Warnings, Precautions, Pregnancy, Nursing, Abuse - Acetylcysteine

Acetadote Warnings, Precautions, Pregnancy, Nursing, Abuse - Acetylcysteine

WARNINGS

Serious anaphylactoid reactions, including death in a patient with asthma, have been reported in patients administered acetylcysteine intravenously.

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. Anaphylactoid reactions (defined as the occurrence of an acute hypersensitivity reaction during acetylcysteine administration including rash, hypotension, wheezing, and/or shortness of breath) have been observed in patients receiving I.V. acetylcysteine for acetaminophen overdose and occurred soon after initiation of the infusion (see ADVERSE REACTIONS section). If a reaction to acetylcysteine involves more than simply flushing and erythema of the skin, it should be treated as an anaphylactoid reaction. This usually entails administering antihistaminic drugs as well as epinephrine in severe cases. In addition, the acetylcysteine infusion may be Interrupted until treatment of the anaphylactoid symptoms has been initiated and then carefully restarted. If the anaphylactoid reaction returns upon reinitiation of treatment or increases in severity, intravenous acetylcysteine should be discontinued and alternative patient management should be considered. For additional information, contact the American Association of Poison Control Centers (1-800-222-1222).

Acetadote should be used with caution in patients with asthma, or where there is a history of bronchospasm. 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 5% dextrose should be reduced as needed (see DOSAGE AND ADMINISTRATION). If volume is not adjusted fluid overload can occur, potentially resulting in hyponatremia, seizure, and death.

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of acetylcysteine.

Acetylcysteine was not genotoxic in the Ames test or the in vivo mouse micronucleus test. It was, however, positive in the in vitro mouse lymphoma cell (L5178Y/TK+/-) forward mutation test.

Treatment of male rats with acetylcysteine at an oral dose of 250 mg/kg/day for 15 weeks (compared to the recommended total human intravenous dose of 300 mg/kg) did not affect the fertility or general reproductive performance.

Teratology studies were performed in rats at oral doses up to 2000 mg/kg/day and in rabbits at oral doses up to 1000 mg/kg/day (compared to the recommended total human intravenous dose of 300 mg/kg) and 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 response, this drug should be used during pregnancy only if clearly needed.

In four pregnant women with acetaminophen toxicity, oral or I.V. acetylcysteine was administered I at the time of delivery. Acetylcysteine crossed the placenta and was measurable in newborn circulation and cord blood of three viable infants following delivery and in cardiac blood of a fourth infant at autopsy (22 weeks gestational age who died 3 hours after birth). No adverse sequelae developed in the three viable infants. All mothers recovered and none of the infants had evidence of acetaminophen poisoning.

I t 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.

No adverse effects were noted during I.V. infusion with acetylcysteine at a mean rate of 8.4 mg/kg/h for 24 hours to 10 preterm newboms ranging in gestational age from 25 to 31 weeks and in weight from 500 to 1380 grams in one study (Study 1) or in 6 newboms ranging in gestational age from 26 to 30 weeks and in weight from 520 to 1335 grams infused with acetylcysteine at 0.1 t o 1.3 mg/kg/h for 6 days (Study 2). Elimination of acetylcysteine was slower in these infants than n adults; mean elimination half-life was 11 hours (Study 1). There are no adequate and well- controlled studies in pediatric patients.

The clinical studies do not provide a sufficient number of geriatric subjects to determine whether the elderly respond differently.