The total dose of Acetylcysteine Injection is 300 mg/kg given as 3 separate doses and administered over a total of 21 hours. Please refer to the guidelines below for dose preparation based upon patient weight. The total volume administered should be adjusted for patients less than 40 kg and for those requiring fluid restriction (see Tables 1 and 2).
2.1 Administration Instructions (Three-Bag Method: Loading, Second and Third Dose)
Dosing for Patients who weigh 5 kg to 20 kg (Table 1):
Loading Dose: 150 mg/kg diluted in 3 mL/kg of diluent* administered over 1 hr
Second Dose: 50 mg/kg diluted in 7 mL/kg of diluent* administered over 4 hrs
Third Dose: 100 mg/kg diluted in 14 mL/kg of diluent* administered over 16 hrs
Dosing for Patients who weigh 21 kg to 40 kg (Table 2):
Loading Dose: 150 mg/kg diluted in 100 mL of diluent* administered over 1 hr
Second Dose: 50 mg/kg diluted in 250 mL of diluent* administered over 4 hrs
Third Dose: 100 mg/kg diluted in 500 mL of diluent* administered over 16 hrs
Dosing for Patients who weigh 41 kg to 100 kg (Table 3):
Loading Dose: 150 mg/kg diluted in 200 mL of diluent* administered over 1 hr
Second Dose: 50 mg/kg diluted in 500 mL of diluent* administered over 4 hrs
Third Dose: 100 mg/kg diluted in 1000 mL of diluent* administered over 16 hrs
Patients Weighing More Than 100 kg
No specific studies have been conducted to evaluate the use of or necessity of dosing adjustments in patients weighing over 100 kg. Limited information is available regarding the dosing requirements of patients that weigh more than 100 kg. The dose of acetylcysteine recommended in these patients should be a loading dose of 15,000 mg infused over a period of one hour followed by a first maintenance dose of 5,000 mg over 4 hours and a second maintenance dose of 10,000 mg over 16 hours (See Table 3).
Continued Therapy beyond 21 Hours
While there is no clinical trial data to support infusions beyond 21 hours there is literature that supports continued infusion of acetylcysteine in some rare instances. In cases of suspected massive overdose, or with concomitant ingestion of other substances, or in patients with preexisting liver disease, the absorption and/or the half-life of acetaminophen may be prolonged, in such cases consideration should be given to the need for continued infusion of N-acetylcysteine beyond 21 hours. Acetaminophen levels and ALT/AST & INR should be checked before the end of the 21-hour infusion. If acetaminophen levels are still detectable, or in cases in which the ALT/AST are still increasing or the INR remains elevated, the infusion should be continued, and the treating physician should contact a US regional poison center at 1-800-222-1222, or alternatively, a “special health professional assistance line for acetaminophen overdose” at 1-800-525-6115 for assistance with dosing recommendations.
2.2 Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction
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 diluent should be reduced as clinically needed. If the volume of the infusion is not adjusted, fluid overload can occur, potentially resulting in hyponatremia, seizure and death. [see Dosage and Administration (2)].
As acetylcysteine is hyperosmolar (2600 mOsmol/L), caution is advised when the diluent volume is decreased as the hyperosmolarity of the solution is increased. See Table 4 below for examples.
Single dose vial, preservative-free, discard unused portion. If vial was previously opened, do not use for intravenous administration.
Stability studies indicate that the diluted solution is stable for 24 hours at controlled room temperature.
Note: The color of acetylcysteine may turn from essentially colorless to a slight pink or purple once the stopper is punctured. The color change does not affect the quality of the product.
2.3 Renal Impairment
No data are available to determine if a dose adjustment in patients with moderate or severe renal impairment is required.
2.4 Hepatic Impairment
Although there was a threefold increase in acetylcysteine plasma concentrations in patients with hepatic cirrhosis, no data are available to determine if a dose adjustment in these patients is required. The published medical literature does not indicate that the dose of acetylcysteine in patients with hepatic impairment should be reduced.
