title: Colchicine-induced toxicity in a heart transplant patient with chronic renal failure.
abstract: Introduction. Therapeutic doses of colchicine in patients with renal compromise and cyclosporine therapy may result in increased plasma concentrations of colchicine and colchicine toxicity. Case Report. A 60-year-old heart transplant patient with chronic renal failure and cyclosporine-induced immunosuppression was started on colchicine for suspected gout. Four days later, he developed multi-organ failure with rhabdomyolysis, liver damage, polyneuropathy, and cardiotoxicity. Colchicine intoxication was suspected and plasma levels were 7 ng/mL 36 hours after the sixth dose. Neutropenia with an absolute neutrophil count of 700 cells/mm3 was observed five days after colchicine discontinuation. Drug discontinuation, supportive care, antibiotic therapy for a concurrent infection, and G-CSF administration resulted in recovery and he was discharged from the hospital 3 weeks later. Discussion. Cyclosporine co-administration increases colchicine toxicity by a dual mechanism: cyclosporine inhibits P-glycoprotein resulting in increased intracellular colchicine concentrations and decreased hepatic and renal excretion of the drug and cyclosporine interacts with CYP3A4 to decreases the hepatic elimination of colchicine. On the other hand, colchicine may increase cyclosporine neurotoxicity by an addictive mechanism. Conclusions. Shortterm administration of therapeutic colchicine doses may cause life-threatening side effects in cyclosporine-treated patients with renal failure.
authors.affiliation: Clinical Toxicology, Hospital of Bergamo "Ospedali Riuniti", Bergamo, Italy
authors.forename: Giorgio
authors.initials: G
authors.lastname: Eleftheriou
authors.forename: Guiseppe
authors.initials: G
authors.lastname: Bacis
authors.forename: Roberto
authors.initials: R
authors.lastname: Fiocchi
authors.forename: Roberta
authors.initials: R
authors.lastname: Sebastiano
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000378:metabolism; D003078:Colchicine / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016572:Cyclosporine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D006073:Gout / Q000150:complications / Q000188:drug therapy; D006074:Gout Suppressants / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D008875:Middle Aged; D020258:Neurotoxicity Syndromes / Q000209:etiology; D009503:Neutropenia / Q000139:chemically induced
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006074:Gout Suppressants; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D003078:Colchicine