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Acute Colchicine Intoxication During Clarithromycin Administration

Chief Resident, Internal Medicine, Cochin Hospital, Paris, France

Olivier Pajot, MD

Resident, Internal Medicine, Cochin Hospital

Laurence Chauvelot-Moachon, MD

Assistant, Pharmacovigilance Centre, Cochin-Saint Vincent de Paul Hospital, Paris

Eve M Nazal, MD

Resident, Internal Medicine, Cochin Hospital

Charikleia Kélaïdi, MD

Resident, Internal Medicine, Cochin Hospital

Philippe Blanche, MD

Assistant, Internal Medicine, Cochin Hospital

Reprints: Florence Rollot MD, Internal Medicine, Cochin Hospital, Paris 75014, France, fax 33 1 58 41 20 80, florence.rollot{at}cch.ap-hop-paris.fr

OBJECTIVE: To report a case of colchicine intoxication occurring with institution of clarithromycin.

CASE SUMMARY: 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.

DISCUSSION: Continuous colchicine administration is used in treatment of microcrystalline arthritis, Behçet'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.

Key Words: clarithromycin, colchicine, P-glycoprotein

Published Online, October 19, 2004. www.theannals.com, DOI 10.1345/aph.1E197

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