Clevudine myopathy in patients with chronic hepatitis B

Abstract

Clevudine (L-FMAU) is a thymidine l-nucleoside analogue that was recently introduced for the treatment of chronic hepatitis B virus infection. Previous studies showed that clevudine has potent and sustained antiviral activity without causing viral resistance. No severe adverse event occurred during clinical trials. We describe two cases of drug-induced myopathy during long-term treatment of chronic hepatitis B with clevudine.

A comparison of 48-week treatment efficacy between clevudine and entecavir in treatment-naïve patients with chronic hepatitis B

“…Considering that the mutation of rtM204 shows cross-resistance against other L-nucleoside, such as lamivudine, emtricitabine, and tebivudine, the addition of nucleotide analogs including adeforvir and tenofovir may be preferred for patients with clevudineresistant CHB. In a period following the announcement of Pharmasset Inc., several cases of myopathy were reported to be associated with long-term therapy with clevudine, which was characterized by depletion of mitochondrial DNA [15,[21][22][23]. However, KFDA approved continued marketing based on that the risk of infrequent and reversible adverse event was not prior to the advantage of continuing clevudine (http://www.kfda.go.kr).…”

Clevudine-induced viral response, associated with continued reduction of HBsAg titer, was durable after the withdrawal of therapy

“…Recently, several cases of myopathy, which was characterized by the depletion of mitochondrial DNA, were reported to be associated with long-term therapy with clevudine [21,22]. Although most cases resolved after discontinuation of the drug, the development and approval of clevudine have been halted in the United States, Europe, and many other regions throughout the world.…”

Toxic Myopathies

“…As the authors suggest, this in vitro assay may be an efficient model in which to test potential mitochondrial toxicity of other similarly structured drugs during their development. a new pyrimidine nucleoside analog drug for hepatitis B, also causes characteristic mtDNA depletion, profuse COXnegative fibers [128,129], and myonecrosis [130,131]. The mechanism of myotoxicity is therefore likely to be identical to that of zidovudine.…”