Drug Interactions between colchicine and vimseltinib

Consumer information for this interaction is not currently available.

CONTRAINDICATED: Coadministration with inhibitors of P-glycoprotein (P-gp) may significantly increase the serum concentrations of colchicine in patients with renal or hepatic impairment. The mechanism involves enhanced absorption as well as reduced excretion of colchicine due to inhibition of the P-gp efflux transporter in the intestine, renal proximal tubule, and liver. Clinical manifestations associated with the interaction have included neuromyopathy, rhabdomyolysis, hepato- and nephrotoxicity, cardiotoxicity, bone marrow suppression, multiorgan failure, and fatality.

ADJUST DOSE: Coadministration with inhibitors of P-glycoprotein (P-gp) may significantly increase the serum concentrations of colchicine in patient with normal hepatic and renal function. 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). In addition, 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. A similar interaction is expected with other P-gp inhibitors.

MANAGEMENT: Please consult the product labeling for the specific brand of colchicine being used for complete dosing information.
For the Lodoco brand, the use of colchicine and P-gp inhibitors is considered contraindicated in all patients.
For the Colcrys brand, the use of colchicine and P-gp inhibitors in patients with renal or hepatic impairment is considered contraindicated. 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. For the prophylaxis of gout flares, if the original dose was 0.6 mg twice a day the adjusted dosage recommended is 0.3 mg once a day. If the original dose was 0.6 mg once a day the adjusted dosage recommended is 0.3 mg once every other day. For the treatment of 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 recommended daily dosage of colchicine is 0.6 mg/day (may be given as 0.3 mg twice a day).
For the brands Gloperba and Mitigare, the use of colchicine and dual P-gp and CYP450 3A4 inhibitors in patients with renal or hepatic impairment is considered contraindicated. In patients with normal renal and hepatic function, the use of colchicine and P-gp inhibitors should be generally avoided. If coadministration is required, the dose of colchicine should be adjusted by reducing the dose or reducing the dose frequency and the patient should be closely monitored for signs of colchicine toxicity.