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Drug Interactions between danicopan and Probenecid and Colchicine

This report displays the potential drug interactions for the following 2 drugs:

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Major

colchicine danicopan

Applies to: Probenecid and Colchicine (colchicine / probenecid) and danicopan

Consumer information for this interaction is not currently available.

ADJUST DOSE: Coadministration with inhibitors of P-glycoprotein (P-gp) may significantly increase the serum concentrations of colchicine. The mechanism involves enhanced absorption as well as reduced excretion of colchicine due to inhibition of P-gp efflux transporter in the intestine, renal proximal tubule, and liver. In a study of 23 healthy volunteers, administration of a single 0.6 mg dose of colchicine in combination with a single 100 mg dose of the potent P-gp inhibitor cyclosporine resulted in an approximately 3.5-fold increase in colchicine peak plasma concentration (Cmax) and systemic exposure (AUC). Clinical manifestations associated with the interaction have included neuromyopathy, rhabdomyolysis, hepato- and nephrotoxicity, cardiotoxicity, bone marrow suppression, multiorgan failure, and fatality. In a retrospective study of renal transplant recipients at a French hospital, investigators reported that five out of ten patients who received cyclosporine in combination with colchicine experienced muscular symptoms, while none did in the control group that received only cyclosporine. Muscular histology, when performed, was consistent with previous reports of colchicine (i.e., vacuolar) myopathy. Mean duration of colchicine therapy was 12.2 months in the patients with muscular symptoms and 6.8 months in the patients without muscular symptoms. All five patients improved after colchicine withdrawal. No significant differences were found for age, gender ratio, transplant duration, serum creatinine levels, or cumulative steroid dose between case patients and controls. Data are not available for colchicine in combination with other P-gp inhibitors. However, a similar interaction is expected.

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 P-glycoprotein inhibitors such as cyclosporine, carvedilol, amiodarone, bepridil, quinidine, quinine, propafenone, ranolazine, spironolactone, tamoxifen, ulipristal, and some tyrosine kinase inhibitors. In patients with normal renal and hepatic function, the dosage of colchicine should be reduced when used with P-gp inhibitors or within 14 days of using them. Some authorities have specified dose adjustments for gout (treatment and prophylaxis) and familial Mediterranean fever. For the treatment of acute gout flares, the adjusted dosage recommended is 0.6 mg for one dose. 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 (may be given as 0.3 mg twice a day) when used in the presence of a P-gp inhibitor. 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.

References

  1. Arellano F, Krupp P "Muscular disorders associated with cyclosporin." Lancet 337 (1991): 915
  2. Kuncl RW, Duncan G, Watson D, et al. "Colchicine myopathy and neuropathy." N Engl J Med 316 (1987): 1562-8
  3. Rieger EH, Halasz NA, Wahlstrom HE "Colchicine neuromyopathy after renal transplantation." Transplantation 49 (1990): 1196-8
  4. Speeg KV, Maldonado AL, Liaci J, Muirhead D "Effect of cyclosporine on colchicine secretion by the kidney multidrug transporter studied in vivo." J Pharmacol Exp Ther 261 (1992): 50-5
  5. Yussim A, Barnathan N, Lustig S, Shaharabani E, Geier E, Shmuely D, Nakache R, Shapira Z "Gastrointestinal, hepatorenal, and neuromuscular toxicity caused by cyclosporine-colchicine interaction in renal transplantation." Transplant Proc 26 (1994): 2825-6
  6. Rumpf KW, Henning HV "Is myopathy in renal transplant patients induced by cyclosporin or colchicine?." Lancet 335 (1990): 800-1
  7. Menta R, Rossi E, Guariglia A, David S, Cambi V "Reversible acute cyclosporin nephrotoxicity induced by colchicine administration." Nephrol Dial Transplant 2 (1987): 380-1
  8. Jonsson J, Gelpi JR, Light JA, Aquino A, Maszaros S "Colchicine-induced myoneuropathy in a renal transplant patient." Transplantation 53 (1992): 1369-71
  9. Gruberg L, Har-Zahav Y, Agranat O, Freimark D "Acute myopathy induced by colchicine in a cyclosporine treated heart transplant recipient: possible role of the multidrug resistance transporter." Transplant Proc 31 (1999): 2157-8
  10. Caglar K, Safali M, Yavuz I, Odabasi Z, Yenicesu M, Vural A "Colchicine-induced myopathy with normal creatine phosphokinase level in a renal transplant patient." Nephron 92 (2002): 922-924
  11. Fujii Y, Arimura Y, Takahashi N, et al. "[A case of Behcet's disease associated with neuromyopathy induced by combination therapy with colchicine and cyclosporin]" Ryumachi 43 (2003): 44-50
  12. Minetti EE, Minetti L "Multiple organ failure in a kidney transplant patient receiving both colchicine and cyclosporine." J Nephrol 16 (2003): 421-5
  13. Vasudevan AR, Uthamalingam S, Kumar S, Tamarin F, Brensilver JM "Colchicine-induced rhabdomyolysis: the whole is greater than the sum of its parts!" Am J Med 115 (2003): 249
  14. Wilbur K, Makowsky M "Colchicine myotoxicity: case reports and literature review." Pharmacotherapy 24 (2004): 1784-92
  15. Englund G, Hallberg P, Artursson P, Michaelsson K, Melhus H "Association between the number of coadministered P-glycoprotein inhibitors and serum digoxin levels in patients on therapeutic drug monitoring." BMC Med 2 (2004): 8
  16. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  17. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  18. Francis L, Bonilla E, Soforo E, et al. "Fatal toxic myopathy attributed to propofol, methylprednisolone, and cyclosporine after prior exposure to colchicine and simvastatin." Clin Rheumatol 27 (2008): 129-31
  19. Eleftheriou G, Bacis G, Fiocchi R, Sebastiano R "Colchicine-induced toxicity in a heart transplant patient with chronic renal failure." Clin Toxicol (Phila) 46 (2008): 827-30
  20. "Colchicine: serious interactions." Prescrire Int 17 (2008): 151-3
  21. "Product Information. Colcrys (colchicine)." AR Scientific Inc (2009):
  22. Lee BI, Shin SJ, Yoon SN, Choi YJ, Yang CW, Bang BK "Acute myopathy induced by colchicine in a cyclosporine-treated renal transplant recipient--a case report and review of the literature." J Korean Med Sci 12 (1997): 160-1
  23. Ducloux D, Schuller V, Bresson-Vautrin C, Chalopin JM "Colchicine myopathy in renal transplant recipients on cyclosporin." Nephrol Dial Transplant 12 (1997): 2389-92
  24. Garrouste C, Philipponnet C, Kaysi S, Enache I, Tiple A, Heng AE "Severe colchicine intoxication in a renal transplant recipient on cyclosporine." Transplant Proc 44 (2012): 2851-2
  25. Volpe DA, Hamed SS, Zhang LK "Use of different parameters and equations for calculation of IC50 values in efflux assays: potential sources of variability in IC 50 determination." AAPS J 16 (2014): 172-80
  26. Nakamura T, Kakumoto M, Yamashita K, et al. "Factors influencing the prediction of steady state concentrations of digoxin." Biol Pharm Bull 24 (2001): 403-8
  27. Mounier G, Guy C, Beyens MN, Ratrema M, Massol A, Ollagnier M "Colchicine-induced pancytopenia during therapeutic dose administratioin. French parmacovigilance database survey and literature review." Drug Saf 29 (2006): 911-1010
  28. FDA. U.S. Food and Drug Administration "Postmarket drug safty information for patients and providers. Drugs. Colchicine (marketed as Colcrys) information. http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm174382.htm" (2015):
  29. FDA. U.S. Food and Drug Administration "Information for Healthcare Professionals: New safety information for Colchicine (marketed as Colcrys). http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm174315.htm" (2015):
View all 29 references

Drug and food interactions

Major

colchicine food

Applies to: Probenecid and Colchicine (colchicine / probenecid)

Drinking large amounts of grapefruit juice can increase your blood levels of colchicine to dangerous levels. You should avoid the consumption of grapefruit or grapefruit juice during treatment with colchicine. Let your doctor know if you experience abdominal pain, nausea, vomiting, diarrhea, fever, muscle pain, weakness, fatigue, and/or numbness or tingling in your hands and feet, as these may be early symptoms of colchicine toxicity.

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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