We appreciate the comments from Andrade and Lucena and agree that definitive implication of an individual drug, terbinafine or rabeprazole, as the causative agent in this case of acute fulminant hepatitis is difficult. Terbinafine is known to result in idiosyncratic hepatic damage. Furthermore, terbinafine has been on the market for more than twice as long as rabeprazole, and it has been used in oral form to treat more than 18 million people.1 Although we were unable to determine the number of patients treated with rabeprazole, we suspect it is far fewer. (However, we suspect that far more individuals have been treated with all benzimidazole proton-pump inhibitors than with terbinafine.) Unfortunately, this knowledge and extensive experience with terbinafine may draw attention away from other possible but less well-known agents and result in underestimation of causality in cases of adverse reactions by clinicians and diagnostic scales such as the CIOMS scale.
Berger C, Johnstone D, Fleckman P. Acute Fulminant Hepatitis After Treatment With Rabeprazole and Terbinafine: Is Rabeprazole the Culprit?—Reply. Arch Intern Med. 2002;162(3):360–361. doi:
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