P-166: Hepatocellular necrosis associated with labetalol

• Published in: American journal of hypertension 2005-05, Vol.18 (S4), p.67A-67A
• Main Authors: Long, Robert C., King, Deborah S., Wofford, Marion R., Harkins, Kimberly G., Stewart, Jimmy L.
• Format: Article
• Language: English
• Subjects: Adverse Effects; Antihypertensive Medications
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/j.amjhyper.2005.03.184

Hepatocellular injury secondary to antihypertensive therapy is a rare complication. It has been described with calcium channel blockers, angiotensin converting enzyme inhibitors, thiazide diuretics, hydralazine and beta blockers but is best characterized in association with methyldopa. There have been case reports of labetalol-induced hepatitis and the manufacturer's package insert was revised after a series of 11 cases published in 1991. This side effect of labetalol is not commonly listed in tables of drug-induced hepatotoxicity and can be overlooked because of its rarity. A 51-year-old female with severe uncontrolled hypertension, BP of 200/100, was referred to a tertiary care hypertension clinic and started on labetalol. She denied history of ethanol abuse or intravenous drug use. Past medical history was significant for methyldopa-induced hepatitis 17 years prior and a blood transfusion 22 years prior, secondary to blood loss from a gynecology procedure. All laboratory assessments were normal. Approximately 3 months after starting labetalol she presented with a 1–2 week history of nausea, abdominal pain, fatigue and dark urine. She was admitted to the hospital, her home antihypertensive medications were held and nicardipine was used for blood pressure control. On physical exam she was jaundiced with icteric sclera and a slightly tender liver that was palpable 2 cm below the costal margin. Labs revealed total bilirubin of 24, alanine transaminase 3813, aspartate transaminase 5228, prothrombin time 22.3 (INR 2.0). Extensive testing for autoimmune and infectious causes of hepatitis were negative. A liver biopsy showed acute hepatitis with bridging necrosis. During her hospitalization she developed fulminant hepatic failure, hepatic encephalopathy and hepatorenal syndrome. She required liver transplant and is now stable. This case emphasizes the importance of appreciating the potential of labetalol to cause hepatocellular necrosis severe enough to require a liver transplant. It is important to keep all medications in mind when a patient presents with elevated liver enzymes. We found no known reports of labetalol and methyldopa hepatotoxicity occurring in the same patient. It may be prudent to follow patients with a history of idiosyncratic hepatitis secondary to drug therapy more closely when initiating medications that have been associated with liver toxicity.