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15 December 1998 | Volume 129 Issue 12 | Page 1080
We read with interest Dr. Whitcomb's letter concerning, among other issues, hepatotoxicity associated with troglitazone [1]. According to experience in clinical trials to date, troglitazone-related hepatotoxicity is usually asymptomatic, mild, and reversible. However, clinical trial experience of drug toxicity often underestimates the prevalence and severity of adverse events observed during postmarketing use [2]. News of six deaths and one liver transplantation associated with troglitazone led to withdrawal of the product from the British market [3]. We describe another case of fatal hepatitis associated with troglitazone.
An 85-year-old man with type 2 diabetes presented with severe hepatic dysfunction. He had been treated with insulin for 10 years, and troglitazone therapy had been started by his local physician 5 months before presentation. The dosage was increased to 400 mg/d after 15 weeks of therapy. Abdominal pain, malaise, and jaundice subsequently developed, and the alanine aminotransferase level was 608 U/L. Troglitazone therapy was discontinued, and the patient was referred to our institution. At presentation, he was receiving 73 U of insulin daily. Other medications included metoprolol, 50 mg, and levothyroxine, 0.05 mg once daily.
Physical examination revealed jaundice. Laboratory investigations included an alanine aminotransferase level of 287 U/L (normal, 10 to 45 U/L), a total bilirubin level of 15.6 mg/dL (normal, 0.1 to 1.1 mg/dL), an albumin level of 2.5 g/dL (normal, 3.5 to 5 g/dL), a normal prothrombin time, and a glycosylated hemoglobin value of 5.2%. Serologic testing for hepatitis A, B, and C had negative results, and a hepatic ultrasonogram was normal.
A diagnosis of troglitazone-induced hepatitis seemed likely. The patient's symptoms progressed; confusion, agitation, ascites, and edema developed; and the patient was hospitalized. Liver biopsy showed submassive hepatic necrosis (Figure 1). Despite aggressive medical therapy, the patient's condition progressively deteriorated and he died 8 weeks after presentation. LETTER
Fatal Hepatotoxicity Associated with Troglitazone
TO THE EDITOR:
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Troglitazone, when given with insulin, improves glycemic control in patients with type 2 diabetes [4]. In rare cases, however, its use is associated with fatal hepatotoxicity. Our case emphasizes the importance of adherence to the current prescribing and monitoring guidelines recommended by the manufacturer and the U.S. Food and Drug Administration [5]. It remains uncertain whether adherence to these guidelines will prevent similar cases.
Author and Article Information
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References
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TopAuthor & Article InfoReferences |
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1. Whitcomb RW. Update in endocrinology [Letter]. Ann Intern Med. 1998; 128:871.
2. de Groen PC, Lubbe DF, Hirsch LJ, Daifotis A, Stephenson W, Freed-holm D, et al. Esophagitis associated with the use of alendronate. N Engl J Med. 1996; 335:1016-21.
3. Troglitazone suspended in UK after more adverse events. SCRIP. 1997; 2290:15.
4. Schwartz S, Raskin P, Fonseca V, Graveline JF. Effect of troglitazone in insulin-treated patients with type II diabetes mellitus. N Engl J Med. 1998; 338:861-6.
5. Physicians' Desk Reference. Montvale, NJ: Medical Economics Pr; 1998:2118-21.
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