Colchicine Clarithromycin

Oral colchicine causes dose-dependent GI adverse effects (nausea, vomiting, and diarrhea) in 50% to 80% of patients before relief of the attack. Non-GI adverse effects include neutropenia and axonal neuromyopathy, which may be worsened in patients taking other myopathic drugs (e.g., statins) or in those with renal insufficiency. Colchicine should not be used concurrently with macrolide antibiotics (especially clarithromycin) because reduced biliary excretion may lead to increased plasma colchicine levels and agranulocytosis. 

COLCHICINE MACROLIDES Case reports of colchicine toxicity when macrolides were added Uncertain macrolides possibly inhibit hepatic metabolism of colchicine. Clarithromycin and erythromycin both inhibit intestinal P-gp, which may t bioavailability of colchicine Monitor FBC and renal function closely... 

Fatal colchicine intoxication occurred in a 67-year-old man who had taken clarithromycin 500 mg bd for 4 days (57). 

Clarithromycin may have inhibited colchicine metabolism and caused a rise in colchicine concentration. 

Dogukan A, Oymak FS, Taskapan H, Guven M, Tokgoz B, Utas C. Acute fatal colchicine intoxication in a patient on continuous ambulatory peritoneal dialysis (CAPD). Possible role of clarithromycin administration. Clin Nephrol 2001 55(2) 181-2. 

Two further cases of fatal agranulocytosis, presumed to result from use of colchicine with clarithromycin, have been reported, and 2 other cases describe colchicine toxicity during clarithromycin use in patients with renal impairment. ... 

Erythromycin and clarithromycin may inhibit the hepatic metabolism of colchicine via the cytochrome P450 isoenzyme CYP3A4, and/or might increase its bioavailability via effects on P-glycoprotein. - These effects would be more marked in patients with renal impairment. 

Caraco Y, Puttemian C, Rahamimov R, Ben-Chetrit E Acute colchicine intoxication-possible role of erythromycin administration J Rheumatol (1992) 19,494-6 2 Rollot F, Pajot O, Chauvelot-Moachon L, Nazal EM, Kelaidi C, Blanche P Acute colchicine intoxication durii clarithromycin administration Ann Pharmacother (2004) 38,... 

Hung IFN, Wu AKL, C3iei VCC, Tang BSF, To KW, Yeui CK, Woo PCY, Lau SKP, Cheung BMY, Yuen KY. Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency a reboq)ective stixfy. Clin Infect Dis (2005) 41,291—300. 

Akdag I, Ersoy A, Kahvecic hi S, GuUulu M, Dilek K. Acute colchicine intoxication during clarithromycin administration in patients with chronic renal ihire.JM hn9/(2006) 19,515— 17. 

Several case reports describe acute life-threatening colchicine toxicity caused by the addition of erythromycin or clarithromycin, and one retrospective study found that 9 of 88 patients who had received the combination of colchicine and clarithromycin died. 

Drug-drug iuteractions Colchicine is metabolized by CYP3A4 and transported by P glycoprotein. It can therefore accumulate and have toxic effects during concomitant therapy with inhibitors of CYP3A4 and P glycoprotein, such as clarithromycin, disulfiram, and ciclosporin. Three such cases have been described [93, 94, 95 ]. 

McKinnell J, Tayek JA. Short term treatment with clarithromycin resulting in colchicine-induced rhabdomyolysis. J Clin Rheumatol 2009 15(6) 303-5. 

Drug-drug interactions Colchicine Rhabdomyolysis occurred in a 48-year-old African-American man with hypertension and chronic gout, who was taking colchicine 0.6 mg/day and who took clarithromycin 500 mg bd for 3 days for a community-acquired pneumonia [130" ]. The serum aminotransferases rose and the serum creatine kinase activity was 22 996 U/1 the urine contained myoglobin. Withdrawal of colchicine and clarithromycin resulted in clinical and biochemical resolution. 

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