Drug interactions between clarithromycin and colchicine

ADJUST DOSE: Coadministration with inhibitors of CYP450 3A4 may significantly increase the serum concentrations of colchicine, which is primarily metabolized by the isoenzyme. Clinical toxicity including myopathy, pancytopenia, and multiple organ failure may occur. In one case report, a patient with familial Mediterranean fever and amyloidosis involving the kidney, liver, and gastrointestinal tract was admitted to the hospital with life-threatening colchicine toxicity after a two-week course of erythromycin, a moderate CYP450 3A4 inhibitor. During the year prior to admission, the patient had developed recurrent diarrhea and abdominal pain and demonstrated toxic levels of colchicine on two occasions. It is likely the patient had acute colchicine toxicity brought on by the addition of erythromycin and superimposed on chronic colchicine intoxication secondary to renal and hepatic impairment. The patient improved with supportive therapy and intensive hemodialysis and was discharged on day 70 of hospitalization. Another report describes two fatal cases of agranulocytosis due to presumed interaction between colchicine and clarithromycin, a potent CYP450 3A4 inhibitor. One patient had mild liver function test abnormalities, while the other patient had end-stage renal failure and was on continuous ambulatory peritoneal dialysis.

MANAGEMENT: Due to the risk of life-threatening and fatal toxicity, patients with renal or hepatic impairment should not be given colchicine in combination with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, nefazodone, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics. In patients with normal renal and hepatic function, the dosage of colchicine should be reduced when used with potent CYP450 3A4 inhibitors or within 14 days of using them. For the treatment of acute gout flares, the adjusted dosage recommended is 0.6 mg for one dose, followed by 0.3 mg one hour later. Administration should not be repeated for at least three days. For the treatment of familial Mediterranean fever, the maximum dosage of colchicine is 0.6 mg/day when used in the presence of potent CYP450 3A4 inhibitors. Patients should be advised to contact their physician if they experience symptoms of toxicity such as abdominal pain, nausea, vomiting, diarrhea, fatigue, myalgia, asthenia, hyporeflexia, paresthesia, and numbness.