NAC dosing by oral (PO) or intravenous (IV) route
Measured Factor Detail
NAC is an antidote for acetaminophen overdose that prevents hepatic injury after an ingestion of a hepatotoxic quantity of acetaminophen. NAC can be given by oral route with Mucomyst or Cetylev or by intravenous route with Acetadote. On the other hand, patients at risk of developing hepatotoxicity after acetaminophen overdose are identified using the Rumack-Matthew nomogram. The Rumack-Matthew nomogram and dosage of Acetadote are available at http://acetadote.com/acetadote-prescribing-information-11-2016.pdf . The Rumack-Matthew nomogram and dosage of Cetylev are available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207916s000lbl.pdf .
Measured Factor High Impact
- A blood test is used to determine plasma or serum acetaminophen concentration at least 4 hours after ingestion in order to determine the need for continued treatment with NAC.
- Critical High: Dosing of NAC is dependent on patient's weight and plasma/serum concentration of acetaminophen.
- Normal: No acetaminophen overdose based on the plasma/serum concentration of acetaminophen and the Rumack-Matthew nomogram.
- Normal Adult Male: No acetaminophen overdose based on the plasma/serum concentration of acetaminophen and the Rumack-Matthew nomogram.
- Normal Adult Female: No acetaminophen overdose based on the plasma/serum concentration of acetaminophen and the Rumack-Matthew nomogram.
- Normal Pediatric: No acetaminophen overdose based on the plasma/serum concentration of acetaminophen and the Rumack-Matthew nomogram.
- Normal Geriatric Male: No acetaminophen overdose based on the plasma/serum concentration of acetaminophen and the Rumack-Matthew nomogram.
- Normal Geriatric Female: No acetaminophen overdose based on the plasma/serum concentration of acetaminophen and the Rumack-Matthew nomogram.
NAC is most effective during the first 16 hours after acute ingestion of an acetaminophen overdose. The longer the patients are withheld from NAC treatment, the less effective NAC treatment becomes. Patients treated within 16 hours after ingestion had less hepatic toxicity than those treated between 16 and 24 hours after ingestion. Moreover, the acetaminophen blood level should be obtained 4 hours or more after ingestion of an acetaminophen overdose, because acetaminophen levels obtained before 4 hours may not represent its peak plasma levels.
Study Validation 1
This study described the outcomes of 2540 patients with acetaminophen ingestions treated with a loading dose of 140 mg of oral N-acetylcysteine per kilogram of body weight, followed four hours later by 70 mg per kilogram given every four hours for an additional 17 doses. Hepatotoxicity developed in 6.1% of patients when N-acetylcysteine was started within 10 hours of acetaminophen ingestion, as compared with in 26.4% of patients when therapy was started 10 to 24 hours after ingestion and in 41% of patients who were treated 16 to 24 hours after ingestion. There were 11 deaths among the 2540 patients, with nine cases associated with elevated aminotransferase before N-acetylcysteine was started. The best time window for treatment providing protection from hepatotoxicity was eight hours, regardless of the initial plasma acetaminophen concentration. However, treatment should still be indicated as late as 24 hours after ingestion.
Study Validation 2
A total of 100 patients with paracetamol (acetaminophen) overdose were treated with intravenous N-acetylcysteine, and 40 of them who were treated within eight hours after ingestion had complete protection against liver damage. Only 1 out of 62 patients treated within 10 hours developed severe liver damage. Additionally, a retrospective analysis of 57 patients treated with supportive care alone showed incidence of hepatotoxicity in 33 patients (58%). The study concluded that the best time window for treatment providing complete protection from severe liver damage was eight hours. Treatment after 15 hours was completely ineffective. Intravenous N-acetylcysteine was more effective than cysteamine and methionine.
Study Validation 3
This retrospective study provided descriptive data on the safety and efficacy of intravenous N-acetylcysteine (IV-NAC) in the treatment of acetaminophen toxicity using the Hunter Area Toxicology Service (HATS) database. Of the 399 patients were treated with IV-NAC, 37 had an adverse drug reaction to IV-NAC, of which 7 were anaphylactoid. There were 5 deaths in hospital, including two attributed to acetaminophen and none due to IV-NAC. Of the 64 patients who were treated with IV-NAC within 8 hours, 2 developed hepatotoxicity, as compared with 32 out of 128 patients receiving IV-NAC after 8 hours fron ingestion (p = 0.0002). IV-NAC treatment within 8 hours after acetaminophen ingestion resulted in 26 patients with hospitalization stay longer than 48 hours, as compared with IV-NAC after 8 hours fron ingestion resulting in 70 patients with hospitalization stay longer than 48 hours (p < 0.0001). The study concluded that when IV-NAC was administered within 8 hours after acetaminophen ingestion, in-hospital death was infrequent and hepatotoxicity was significantly less.
Study Additional 1
This retrospective case series study evaluated the safety and efficacy of a shorter N-acetylcysteine (NAC) regimen in the treatment of acute acetaminophen overdose. A total of 75 patients with an acute acetaminophen overdose, serum acetaminophen concentration in toxic range, received oral treatment with NAC 140 mg/kg, followed by maintenance doses of 70 mg/kg every 4 hours until the serum acetaminophen level was no longer detectable, rather than the standard 72-hour treatment regimen. Twenty-five (33.3%) patients treated for a period of less than 24 hours, 25 (33.3%) were treated for 24 to 36 hours, and 25 (33.3%) were treated for 37 to 64 hours. No patient treated for less than 24 hours had evidence of hepatotoxicity. Hepatotoxicity developed in 2 (8%) patients treated for 24 to 36 hours and in 4 (16%) patients treated for 37 to 64 hours. The study concluded that a shorter course of oral NAC therapy in patients who do not show evidence of hepatotoxicity within 36 hours of an acute acetaminophen overdose was safe and effective.