Hepatitis naproxen

Hepatic function impairment Dose reduction may be needed with naproxen. Use caution in patients with impaired hepatic function or a history of liver disease. 

In another trial the pharmacokinetics of a single dose of naproxen was studied in 11 patients with liver disease (four severe hepatitis with cholestasis two extrahepatic cholestasis one chronic alcoholic cirrhosis two active chronic hepatitis, with and without symptoms one asymptomatic PBC and one asymptomatic hepatic cirrhosis). In two of the seven patients with cholestasis, a significant delay in absorption occurred. In most of the patients studied there was a significant decrease in elimination, increasing the half-life from around 14 hours to 20 hours [41]. 

Calvo MV, Dominguez A, Macias JG, et al. (1980) Naproxen disposition in hepatic and biliary disorders. Int J Clin Pharmacol Ther Toxicol 18 242-246. 

Abnormal liver function tests (SED-9, 152) (17) and hepatic injury have been associated with naproxen (18), but no definite cause-effect relation has been established. 

C. Pharmacokinetics. NSAIDs are generally well absorbed, and volumes of distribution (Vd) are relatively small (eg, 0.15 L/kg for ibuprofen). COX-2 inhibitors have larger volumes of distribution (86-91 L in adults for rofecoxib, 400 L for celecoxib). Most agents are highly protein bound, and most are eliminated through hepatic metabolism and renal excretion with variable half-lives (eg, 1.5-2.5 hours for ibuprofen and 12-17 hours for naproxen). (See also Table 11-59.)... 

Toxicity most commonly begins within 4 hours of ingestion with symptoms such as headache, tinnitus, drowsiness, abdominal pain, nausea, and vomiting. Severe toxicity is reported mainly in children. Severe toxicity occurs with ingestions of 400 mg/kg or more of naproxen with symptoms including seizures, apnea, hypertension, and renal and hepatic dysfunction. 

---