title: Colchicine-induced rhabdomyolysis in a heart/lung transplant patient with concurrent use of cyclosporin, pravastatin, and azithromycin.
abstract: We report a case of colchicine-induced rhabdomyolysis in a heart/lung-transplanted man treated with cyclosporin. A treatment was to resolve an acute gouty arthritis and was started with 3 mg of colchicine the first day, then 2 mg the second and the third day, and finally 1 mg/d during 6 days. Eight days later, the patient developed multiple organ failure and rhabdomyolysis. The concentration of colchicine analyzed was greater than the standard 153 hours after his last intake. Pharmacokinetic interactions are responsible of this toxicity. Cyclosporin, pravastatin, and azithromycin are known to inhibit P-glycoprotein, which will enhance the intracellular colchicine level by acting in its bioavailability and moderating hepatic and renal excretion. Moreover, long-term treatment by cyclosporin generates chronic renal failure that will, in the same time, decrease colchicine elimination. Even short-term administration of therapeutic colchicine dose may cause colchicine-related toxicity, especially in the setting of a renal failure and/or polymedicinal treatment.
authors.affiliation: Clinical Pharmacology Department and EA 4275 Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, Hospital of the University of Nantes, Nantes, France. regis.bouquie@chu-nantes.fr
authors.forename: Régis
authors.initials: R
authors.lastname: Bouquié
authors.forename: Guillaume
authors.initials: G
authors.lastname: Deslandes
authors.forename: Christian
authors.initials: C
authors.lastname: Renaud
authors.forename: Eric
authors.initials: E
authors.lastname: Dailly
authors.forename: Alain
authors.initials: A
authors.lastname: Haloun
authors.forename: Pascale
authors.initials: P
authors.lastname: Jolliet
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D017963:Azithromycin / Q000627:therapeutic use; D003078:Colchicine / Q000009:adverse effects*; D016572:Cyclosporine / Q000627:therapeutic use; D003550:Cystic Fibrosis / Q000601:surgery; D004347:Drug Interactions; D006073:Gout / Q000188:drug therapy / Q000453:epidemiology; D006074:Gout Suppressants / Q000009:adverse effects*; D016041:Heart-Lung Transplantation / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000453:epidemiology; D008297:Male; D009102:Multiple Organ Failure; D017035:Pravastatin / Q000627:therapeutic use; D012206:Rhabdomyolysis / Q000139:chemically induced*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000900:Anti-Bacterial Agents; D000924:Anticholesteremic Agents; D006074:Gout Suppressants; D007166:Immunosuppressive Agents; D017963:Azithromycin; D016572:Cyclosporine; D017035:Pravastatin; D003078:Colchicine