Symptomatology
Patients usually present with vague symptoms that may include nausea, anorexia, fatigue, right upper-quadrant discomfort, jaundice, or dark urine. Patients with cholestatic liver disease may also present with pruritus.
Any of these along with laboratory evidence of liver injury should indicate further investigation into possible DILI. Impaired hepatic function such as increased prothrombin time and encephalopathy (signs of acute liver failure) indicate severe hepatic injury.
The Agents
Common causes of hepatocellular injury include: acetaminophen, fluoxetine, highly active antiretroviral therapies, kava kava (other herbal products), non-steroidal anti-inflammatory drugs, paroxetine, rifampin, risperidone, statins, trazodone, and troglitazone.
Common causes of cholestatic injury include: ampicillin-clavulanic acid, anabolic steroids, chlorpromazine, clopidogrel, estrogens, mirtazapine, terbinafine, and tricyclics.
Common causes of mixed-pattern injury include: amitriptyline, azathioprine, captopril, carbamazepine, enalapril, erythromycins, flutamide, phenytoin, sulfonamides, trazodone, and trimethoprim-sulfamethoxazole.
Most cases of non-fulminant hepatitis will improve upon cessation of offending or potentially offending agent(s). Assess hepatic injury immediately via continuously obtained biochemical tests.
Consult a hepatologist or gastroenterologist immediately if jaundice, impaired hepatic function or clinical signs of acute hepatic failure (e.g., encephalopathy) are evident.
Report all cases of potential DILI to the FDA’s adverse events reporting program, Medwatch, at www.fda.gov/ medwatch or by calling (800) 332-1088. For patients receiving potentially hepatotoxic agents, liver function test monitoring is recommended following a baseline assessment. Some agents require monthly rather than periodic monitoring. For a list of some agents that require hepatic monitoring and the recommended frequency, visit www.factsandcomparisons.com/assets/hospitalpharm/feb2002_HepSp.pdf.5 TH
Michele B. Kaufman is a freelance medical writer based in New York City.
References
- Nathwani RA, Kaplowitz N. Drug hepatotoxicity. Clin Liver Dis. 2006;10:207-217.
- Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med. 2006;354(7):731-739.
- Hepatic Toxicity Possibly Associated with Kava-Containing Products—United States, Germany, and Switzerland, 1999-2002. MMWR Weekly, Nov. 29, 2002/51(47):1065-1067. Available at: www.cdc.gov/MMWR/previews/mmwrhtml/mm5147a1.htm. Last accessed Nov. 5, 2007.
- Lasser KE, Allen PD, Woolhandler SJ, et al. Timing of new black box warnings and withdrawals for prescription medications. JAMA. 2002;287:17:2215-2220.
- Tice SA, Parr D. Medications that require hepatic monitoring. Hospital Pharmacy 2004;39(6):595-606.