Acute colchicine intoxication during clarithromycin administration.
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.
Rollot
Florence
F
Internal Medicine, Cochin Hospital, Paris, France.
Pajot
Olivier
O
Chauvelot-Moachon
Laurence
L
Nazal
Eve M
EM
Kélaïdi
Charikleia
C
Blanche
Philippe
P
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
D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D006074:Gout Suppressants; D000658:Amoxicillin; D017291:Clarithromycin; D009853:Omeprazole; D003078:Colchicine