title: Acute colchicine intoxication during clarithromycin administration.
abstract: OBJECTIVE
  To report a case of colchicine intoxication occurring with institution of clarithromycin.
  
  
  METHODS
  A 76-year-old man with familial Mediterranean fever (FMF) had received colchicine 1.5 mg daily for 6 years. The patient underwent 7 days of clarithromycin, amoxicillin, and omeprazole treatment for Helicobacter pylori-associated gastritis. Fever, abdominal pain, and diarrhea occurred 3 days after treatment initiation. On day 8, dehydration, pancytopenia, metabolic acidosis, and increased lipase level necessitated hospitalization. Alopecia was observed 2 weeks later. The patient recovered fully after the colchicine dosage was reduced to 0.5 mg/day and rehydration was performed. The previous dosage was then reinstituted without adverse reaction. An objective causality assessment revealed that the adverse event was probable.
  
  
  CONCLUSIONS
  Continuous colchicine administration is used in treatment of microcrystalline arthritis, Behcet's disease, and FMF. Colchicine is primarily eliminated through biliary excretion. Renal elimination and cytochrome P450 metabolism play a less significant role. Colchicine is also a substrate of P-glycoprotein, a transporter involved in cellular efflux and elimination of numerous drugs. Three cases of intoxication have been reported when colchicine was combined with erythromycin, josamycin, or clarithromycin. Macrolides are inhibitors of P-glycoprotein and cytochrome P450-dependent enzymes and may decrease colchicine's biliary excretion through P-glycoprotein inhibition.
  
  
  CONCLUSIONS
  Coadministration of colchicine and macrolides may impair colchicine elimination, resulting in excess drug exposure and toxicity. To this end, colchicine should be used with extreme caution in patients receiving P-glycoprotein inhibitors, particularly if they are elderly and/or renally compromised.
authors.affiliation: Internal Medicine, Cochin Hospital, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Rollot
authors.forename: Olivier
authors.initials: O
authors.lastname: Pajot
authors.forename: Laurence
authors.initials: L
authors.lastname: Chauvelot-Moachon
authors.forename: Eve M
authors.initials: EM
authors.lastname: Nazal
authors.forename: Charikleia
authors.initials: C
authors.lastname: Kélaïdi
authors.forename: Philippe
authors.initials: P
authors.lastname: Blanche
mesh_terms: D000368:Aged; D000658:Amoxicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D017291:Clarithromycin / Q000009:adverse effects* / Q000627:therapeutic use; D003078:Colchicine / Q000009:adverse effects*; D004347:Drug Interactions; D010505:Familial Mediterranean Fever / Q000150:complications / Q000188:drug therapy; D005756:Gastritis / Q000150:complications / Q000188:drug therapy / Q000382:microbiology; D006074:Gout Suppressants / Q000009:adverse effects*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D006074:Gout Suppressants; D000658:Amoxicillin; D017291:Clarithromycin; D009853:Omeprazole; D003078:Colchicine