Acetylcysteine injection is an antidote for acetaminophen overdose indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen in adults and pediatric patients who weigh 5 kg or greater with an acute ingestion or from repeated supratherapeutic ingestion (RSI) (1). (1)
Pre-Treatment Assessment Following Acute Ingestion (2.1):
Prior to initiating treatment with Acetylcysteine injection, decide whether the three-bag or two-bag regimen will be used.
Obtain a plasma or serum sample to assay for acetaminophen concentration at least 4 hours after ingestion.
* If the time of acetaminophen ingestion is unknown:
o Administer a loading dose of Acetylcysteine injection immediately.
o Obtain an acetaminophen concentration to determine need for continued treatment.
* If the acetaminophen concentration cannot be obtained (or is unavailable or uninterpretable) within the 8-hour time interval after acetaminophen ingestion or there is clinical evidence of acetaminophen toxicity:
o Administer a loading dose of Acetylcysteine injection immediately and continue treatment for a total of two doses over 20 hours or three doses over 21 hours (2.5).
* If the patient presents more than 8 hours after ingestion and the time of acute acetaminophen ingestion is known:
o Administer a loading dose of Acetylcysteine injection immediately
o Obtain acetaminophen concentration to determine need for continued treatment
* If the patient presents less than 8 hours after ingestion and the time of acute acetaminophen ingestion is known and the acetaminophen concentration is known:
o Use the revised Rumack-Matthew nomogram (Figure 1) to determine whether or not to initiate treatment with Acetylcysteine injection (2.2) (2)
Nomogram for Estimating Potential for Hepatotoxicity from Acute Acetaminophen Ingestion (2.2):
See Full Prescribing Information for instructions on how to use the nomogram to determine the need for dosing. (2)
Preparation and Storage of Diluted Solution Prior to Administration (2.3):
* Calculate the dose (mg) based on the patient's weight in kg; multiple vials of Acetylcysteine injection may be required.
o Acetylcysteine injection is hyperosmolar (2,600 mOsmol/L), therefore Acetylcysteine injection must be diluted in the recommended volume of sterile water for injection, 0.45% sodium chloride injection, or 5% dextrose in water injection prior to intravenous administration. In general, 0.45% normal saline is the preferred diluent because it provides a more consistent osmolarity profile, reduces the amount of free water delivered to the patient, and better approximates physiologic fluids. (2)
See Full Prescribing Information for examples of osmolarity depending on the type of solution and Acetylcysteine injection concentration. (2)
General Considerations for Selecting the Three-Bag or Two-Bag Regimen (2.4):
* It is not known whether the two-bag regimen is comparable to the three-bag regimen in preventing hepatotoxicity.
* Patients 40 kg or less should receive the three-bag regimen.
* For patients weighing 41 kg or greater, the three-bag regimen may be preferred for those with early signs of severe liver injury or a large acetaminophen ingestion.
Recommended Dosage for Acute Acetaminophen ingestion (2.5):
* Acetylcysteine injection is for intravenous administration only.
* Total dosage of Acetylcysteine injection is 300 mg/kg given intravenously as either:
o 3 separate doses infused over a total of 21 hours
OR
o 2 separate doses infused over a total of 20 hours.
* See Full Prescribing Information for weight-based dosage and weight-based dilution (2.5)
See Full Prescribing Information for recommendations for continuing Acetylcysteine injection treatment after 21 hours (2.2)
Repeated Supratherapeutic Acetaminophen Ingestion (2.6):
* Obtain acetaminophen concentration and other laboratory tests to guide treatment; revised Rumack-Matthew nomogram does not apply. (2)