ACETYLCYSTEINE

5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions, Including Hypotension, Wheezing, Shortness of Breath and Bronchospasm: Observe patients during and after the infusion; immediately discontinue infusion if a serious reaction occurs and initiate appropriate treatment. Acetylcysteine infusion may be carefully restarted after treatment of hypersensitivity has been initiated ( 5.1 ). Fluid Overload: Total volume administered should be reduced for patients weighing less than 40 kg and for those requiring fluid restriction ( 5.2 ). 5.1 Hypersensitivity Reactions Serious acute hypersensitivity reactions during acetylcysteine administration including rash, hypotension, wheezing, and/or shortness of breath, have been observed in patients receiving intravenous acetylcysteine for acetaminophen overdose and occurred soon after initiation of the infusion [see Adverse Reactions ( 6.1 )] . If a severe hypersensitivity reaction occurs, immediately stop the infusion of acetylcysteine and initiate appropriate treatment. One patient with asthma developed bronchospasm and died after intravenous administration of acetylcysteine. Acetylcysteine should be used with caution in patients with asthma, or where there is a history of bronchospasm. Patients with asthma should be closely monitored during initiation of acetylcysteine therapy and throughout acetylcysteine therapy. 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. If a reaction to acetylcysteine involves more than simply flushing and erythema of the skin, it should be treated as a hypersensitivity reaction. Management of less severe hypersensitivity reactions should be based upon the severity of the reaction and include temporary interruption of the infusion and/or administration of antihistaminic drugs. The acetylcysteine infusion may be carefully restarted after treatment of the hypersensitivity symptoms has been initiated; however, if the hypersensitivity reaction returns upon re-initiation of treatment or increases in severity, acetylcysteine should be discontinued and alternative patient management should be considered. 5.2 Fluid Overload The total volume of acetylcysteine 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 needed [see Dosage and Administration ( 2 )] . If volume is not adjusted fluid overload can occur, potentially resulting in hyponatremia, seizure and death. Intravenous administration of acetylcysteine can cause fluid overload, potentially resulting in hyponatremia, seizure and death. To avoid fluid overload, use the recommended dilution shown in Tables 2 , 3 and 4 [see Dosage and Administration ( 2.4 )].