Colchicine Interactions
Acidifying Agents
Alkalinizing Agents
- Clarithromycin
- Conivaptan
- Cyanocobalamin, Vitamin B12
- Cyclosporine
- Diazoxide
- Erythromycin
- Ethanol
- Pyrazinamide, PZA
- Sulfinpyrazone
Sympathomimetics
Colchicine Interactions
Colchicine is an alkaloid that is inhibited by acidifying agents, and its action is potentiated by alkalinizing agents. Examples of acidifying agents are acetohydroxamic acid, ammonium chloride, arginine, methenamine; sodium acid phosphate, methionine, potassium acid phosphate; sodium acid phosphate, potassium phosphate; sodium phosphate, sodium benzoate; sodium phenylacetate, atropine; benzoic acid; hyoscyamine; methenamine; methylene blue; phenylsalicylate, and hyoscyamine, methenamine; methylene blue; phenyl salicylate; sodium biphosphate. Examples of alkalinizing agents are tromethamine, sodium lactate, sodium bicarbonate, sodium acetate, potassium citrate, citric acid; sodium citrate, citric acid; potassium citrate; sodium citrate; and citric acid; potassium citrate. The colchicine dose may need adjustment.
Colchicine may increase the sensitivity to CNS depressants like ethanol. In animals, colchicine depresses the respiratory center. Too much colchicine can cause respiratory arrest. Ethanol ingestion also increases the risk of adverse gastrointestinal effects developing in patients receiving colchicine, and it also can increase serum urate concentrations, diminishing the antigout effects of the drug. Advise patients to avoid alcohol.
The response to sympathomimetics may be enhanced by colchicine. In animals, colchicine constricts blood vessels and causes hypertension by central vasomotor stimulation.
A single case report is noted of cyclosporine nephrotoxicity occurring after the addition of colchicine. Cyclosporine concentrations increased and renal function worsened 2 days after the addition of colchicine. The mechanism appears to be reduced cyclosporine metabolism via p-glycoprotein and CYP3A4 inhibition by colchicine; colchicine increases cyclosporine concentrations. Cyclosporine toxicity (i.e., renal and/or hepatic dysfunction, cholestasis, paresthesias, myopathy) may occur. Although cyclosporine can cause hyperuricemia, it would be prudent to avoid the use of colchicine in patients receiving cyclosporine. In addition, the risk for colchicine toxicity is higher in patients with renal dysfunction.
Both erythromycin and clarithromycin appear to inhibit the metabolism of colchicine, possibly through inhibition of CYP3A4. The addition of either erythromycin or clarithromycin to colchicine therapy has lead to colchicine toxicity manifest as fever, GI symptoms, myalgia, leukopenia. A patient receiving colchicine for 1 year developed colchicine toxicity 2 weeks after the addition of erythromycin. The addition of clarithromycin to the regimen of a patient with end-stage renal disease on continuous ambulatory peritoneal dialysis and receiving colchicine proved fatal; pancytopenia and multiple organ failure was reported as the cause of death. A retrospective study reported that the combination of clarithromycin and colchicine can result in a fatal interaction, especially in patients with renal impairment. The study also reported that in patients who received combination therapy, risk factors independently associated with death included extended overlap of therapy, baseline renal impairment, and the development of pancytopenia. Erythromycin and clarithromycin should be used cautiously, if at all, in patients receiving colchicine chronically. Other macrolides such as azithromycin or dirithromycin do not inhibit CYP3A4 and should be considered as potential alternatives in patients taking colchicine.
Several drugs, including colchicine, have been reported to reduce the absorption of cyanocobalamin, vitamin B12. Colchicine has been shown to induce reversible malabsorption of vitamin B12, apparently by altering the function of ileal mucosa. Although further study of these interactions is necessary, patients receiving these agents concurrently should be monitored for the desired therapeutic response to vitamin B12.
Blood dyscrasias (anemia, leukopenia, agranulocytosis, thrombocytopenia, and aplastic anemia) have rarely been reported with the use of sulfinpyrazone or colchicine alone. One published report associated sulfinpyrazone and colchicine co-therapy with leukemia following long-term treatment of patients with gout. The details of the reported cases (n=2) cannot clearly establish a cause-and-effect relationship. Careful monitoring of patients receiving this combination is recommended during chronic use.
Because pyrazinamide, PZA can increase serum uric acid levels and precipitate gouty attacks, the dosages of antigout agents, including allopurinol, colchicine, probenecid, and sulfinpyrazone, may need to be adjusted.
Diazoxide can cause hyperuricemia. Dosages of concomitantly administered antigout medications, including colchicine, may require adjustment.
Conivaptan is a potent inhibitor of CYP3A4 and may increase plasma concentrations of drugs that are primarily metabolized by CYP3A4. Colchicine is a substrate for CYP3A4. Conivaptan should be used with caution with CYP3A4 substrates, especially those substrates that have a narrow therapeutic range or for which significant increases in serum concentrations may be associated with toxicity. According to the manufacturer, concomitant use of conivaptan with drugs that are primarily metabolized by CYP3A4 should be closely monitored, or the combination should be avoided. If a clinical decision is made to discontinue concomitant drugs at recommended doses, allow an appropriate time interval following the conivaptan administration before resuming these drugs.
[ Last revised: 3/5/2006 2:19:00 PM ]
References
. Lin HY, Rocher LL, McQuillan MA et al. Cyclosporine-induced hyperuricemia and gout. N Engl J Med 1989;321:287 - 292.
. Putterman C, Ben-Chetrit E, Caraco Y et al. Colchicine intoxication: Clinical pharmacology, risk factors, features, and management. Sem Arth Rheum 1991;21:143 - 55.
. Kuncl RW, Duncan G, Watson D et al. Colchicine myopathy and neuropathy. N Engl J Med 1987;316:1562 - 8.
. Caraco Y, Putterman C, Rahamimov R, et al. Acute colchicine intoxication--possible role of erythromycin administration. J Rheumatol 1992;19:494 - 6.
. Dogukan A, Oymak ES, Taskapan H, et al. Acute fatal colchicine intoxication in a patient on continuous ambulatory peritoneal dialysis (CAPD). Possible role of clarithromycin administration. Clin Nephrol 2001;55:181 - 2.
. Hansten PD, Horn JR. Cytochrome P450 Enzymes and Drug Interactions, Table of Cytochrome P450 Substrates, Inhibitors, Inducers and P-glycoprotein and footnotes. In: The Top 100 Drug Interactions - A guide to Patient Management. 2005 Edition. Edmonds, WA: H&H Publications; 2005:157 - 170.
. Neoral® (cyclosporine) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2002 Aug.
. Sandimmune® (cyclosporine) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2002 Mar.
. Hyperstat® (diazoxide) injection package insert. Kenilworth, NJ: Schering Corporation; 1985 Feb.
. Pyrazinamide Tablets USP 500 mg package insert. Marietta, GA: VersaPharm Incorporated; 2001 Apr.
. Minetti EE, Minetti L. Multiple organ failure in a kidney transplant patient receiving both colchicine and cyclosporine. J Nephrol. 2003;16:421 - 5.
. Fam AG. Gout in the elderly. Clinical presentation and treatment. Drugs Aging. 1998;13:229 - 43.
. Nascobal® (cyanocobalamin, vitamin B-12) package insert. Union City, CA: Nastech Pharmaceutical Company Inc.; 2005 Feb.
. Colchicine Injection, USP package insert. Bedford, OH: Bedford Laboratories; 1999 Apr.
. Witwer MW, Schmid FR, Tesar JT. Acute myelomonocytic leukaemia and multiple myeloma after sulphinpyrazone and colchicine treatment of gout. BMJ 1976;2:89.
. Hung IF, Wu AK, Cheng VC, et al. Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study. Clin Infect Dis 2005;41:291 - 300.
. Vaprisol® (conivaptan hydrochloride injection). Deerfield, IL: Astellas Pharma US, Inc.;2005 Dec.
. Colchicine Tablets, USP package insert. Corona, CA: Watson Laboratories, Inc.; 2001 Jun.
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