Usual factors associated with severe hepatotoxicity:
(1) very high serum level of acetaminophen
(2) no therapy or delayed therapy with N-acetylcysteine
Conditions associated with increased risk for severe hepatotoxicity in a patient presenting early and with a relatively low serum acetaminophen concentration:
(1) chronic alcohol abuse
(2) pre-existing liver disease (viral hepatitis, alcoholic hepatitis, other)
(3) intake of enzyme-enhancing (inducing) drugs
(3a) carbamazepine
(3b) phenobarbital
(3c) primidone
(3d) rifampicin
(3e) isoniazid
(3f) omeprazole
(3g) oral contraceptives
(3h) St. John's Wort
(4) conditions associated with endogenous glutathione depletion
(4a) malnutrition
(4b) eating disorders (anorexia, bulimia)
(4c) AIDS
(4d) malabsorption (cystic fibrosis, other)
(4e) acute illness with prolonged vomiting or dehydration
(4f) starvation, fasting or inability to eat
where:
• Phenytoin does not increase the risk according to Rumack (2002).
Staggered doses of acetaminophen taken over a short period of time may make serum levels uninterpretable and so the patient should be treated as high risk..
Patients with one or more risk factors should be treated more aggressively with N-acetylcysteine. A lower serum threshold is used to decide whether or not to give the antidote.
