title: Rhabdomyolysis in a hepatitis C virus infected patient treated with telaprevir and simvastatin.
abstract: A 46-year old man with a chronic hepatitis C virus infection received triple therapy with ribavirin, pegylated interferon and telaprevir. The patient also received simvastatin. One month after starting the antiviral therapy, the patient was admitted to the hospital because he developed rhabdomyolysis. At admission simvastatin and all antiviral drugs were discontinued because toxicity due to a drug-drug interaction was suspected. The creatine kinase peaked at 62,246 IU/L and the patient was treated with intravenous normal saline. The patient's renal function remained unaffected. Fourteen days after hospitalization, creatine kinase level had returned to 230 IU/L and the patient was discharged. Telaprevir was considered the probable causative agent of an interaction with simvastatin according to the Drug Interaction Probability Scale. The interaction is due to inhibition of CYP3A4-mediated simvastatin clearance. Simvastatin plasma concentration increased 30 times in this patient and statin induced muscle toxicity is related to the concentration of the statin in blood. In conclusion, with this case we illustrate that telaprevir as well as statins are susceptible to clinical relevant drug-drug interactions.
authors.affiliation: Department of Pharmacy Nijmegen Institute of Health Sciences (NIHS), Radboud university medical center.
authors.forename: Clara T M M de
authors.initials: CT
authors.lastname: Kanter
authors.affiliation: Afiliacja Department of Pharmacy Nijmegen Institute of Health Sciences (NIHS), Radboud university medical center; Department of Clinical Pharmacy, Rijnstate Hospital, Arnhem, The Netherlands.
authors.forename: Matthijs van
authors.initials: Mv
authors.lastname: Luin
authors.affiliation: Laboratoire de Pharmacocinétique et de Toxicologie, Hôpital de La Timone, Marseille, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Solas
authors.affiliation: Department of Pharmacy Nijmegen Institute of Health Sciences (NIHS), Radboud university medical center.
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
authors.affiliation: Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, The Netherlands.
authors.forename: Jan Maarten
authors.initials: JM
authors.lastname: Vrolijk
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects*; D004347:Drug Interactions; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D012206:Rhabdomyolysis / Q000139:chemically induced*; D012254:Ribavirin / Q000627:therapeutic use; D019821:Simvastatin / Q000009:adverse effects*
chemical_list: D000998:Antiviral Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016898:Interferon-alpha; D009842:Oligopeptides; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; D019821:Simvastatin