Drug Interaction Report

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.

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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You should preferably avoid consumption of grapefruit and grapefruit juice while taking encorafenib. Grapefruit and grapefruit juice can significantly increase the blood levels of encorafenib. This may increase the risk of serious side effects such as bleeding complications, eye and vision problems, liver problems, irregular heart rhythm, and development of new skin cancers. Talk to your doctor if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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