Summary

Verapamil significantly increases colchicine blood levels by inhibiting P-glycoprotein transport, leading to potentially serious colchicine toxicity. This interaction requires careful dose reduction and monitoring when both medications are used together.

Introduction

Colchicine is an anti-inflammatory medication primarily used to treat and prevent gout attacks, as well as familial Mediterranean fever. It works by inhibiting microtubule formation and reducing neutrophil migration. Verapamil is a calcium channel blocker commonly prescribed for hypertension, angina, and certain heart rhythm disorders. It works by blocking calcium channels in the heart and blood vessels, reducing heart rate and blood pressure.

Mechanism of Interaction

The interaction between colchicine and verapamil occurs through inhibition of P-glycoprotein (P-gp), an important drug efflux transporter. Verapamil is a potent P-glycoprotein inhibitor that blocks the transport of colchicine out of cells, particularly in the intestines and kidneys. This inhibition leads to increased absorption and decreased elimination of colchicine, resulting in significantly elevated plasma concentrations. Additionally, verapamil may also inhibit CYP3A4 enzyme activity, which contributes to colchicine metabolism, further increasing colchicine exposure.

Risks and Symptoms

The primary risk of this interaction is colchicine toxicity, which can be life-threatening. Symptoms of colchicine toxicity include severe gastrointestinal effects (nausea, vomiting, diarrhea), bone marrow suppression leading to decreased blood cell counts, muscle weakness, kidney dysfunction, and in severe cases, multi-organ failure. Patients with kidney or liver impairment are at particularly high risk. The interaction can increase colchicine levels by 2-3 fold, significantly raising the risk of dose-dependent adverse effects. Fatal outcomes have been reported when colchicine is combined with P-glycoprotein inhibitors like verapamil.

Management and Precautions

When concurrent use is necessary, colchicine dose reduction is essential. For gout treatment, reduce colchicine dose by 50% or consider alternative dosing schedules. For gout prophylaxis, reduce the dose to 0.3 mg daily or every other day. Monitor patients closely for signs of colchicine toxicity, including gastrointestinal symptoms, muscle weakness, and blood count abnormalities. Regular laboratory monitoring should include complete blood count, liver function tests, and kidney function. Consider alternative medications when possible - other calcium channel blockers with less P-glycoprotein inhibition (such as amlodipine) may be safer options. Patients should be educated about toxicity symptoms and advised to seek immediate medical attention if they occur.

Colchicine interactions with food and lifestyle

Grapefruit juice should be avoided with colchicine as it can significantly increase colchicine blood levels and risk of toxicity. Alcohol consumption should be limited or avoided as it may increase the risk of gastrointestinal side effects and potentially worsen gout symptoms. High-purine foods (such as organ meats, certain seafood, and excessive amounts of red meat) should be limited as they can trigger gout flares, potentially counteracting colchicine's therapeutic effects.

Verapamil interactions with food and lifestyle

Grapefruit and grapefruit juice should be avoided while taking verapamil as they can significantly increase blood levels of the medication, potentially leading to dangerous drops in blood pressure and heart rate. Alcohol consumption should be limited or avoided as it can enhance verapamil's blood pressure-lowering effects and increase the risk of dizziness, fainting, and falls. High-fiber foods or fiber supplements may reduce verapamil absorption when taken at the same time, so it's recommended to separate their administration by at least 2 hours.