Summary

Diltiazem significantly increases colchicine blood levels by inhibiting P-glycoprotein and CYP3A4 enzymes, leading to potentially serious colchicine toxicity. This interaction requires careful dose adjustment 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. Diltiazem is a calcium channel blocker commonly prescribed for hypertension, angina, and certain heart rhythm disorders. It belongs to the non-dihydropyridine class of calcium channel blockers and affects both cardiac and vascular smooth muscle.

Mechanism of Interaction

The interaction between colchicine and diltiazem occurs through multiple pathways. Diltiazem is a moderate inhibitor of both CYP3A4 enzyme and P-glycoprotein transporter, both of which are crucial for colchicine metabolism and elimination. When diltiazem inhibits CYP3A4, it reduces colchicine's hepatic metabolism, while P-glycoprotein inhibition decreases colchicine's renal and biliary elimination. This dual inhibition results in significantly increased colchicine plasma concentrations and prolonged elimination half-life.

Risks and Symptoms

The primary risk of this interaction is colchicine toxicity, which can be life-threatening. Symptoms may include severe gastrointestinal effects (nausea, vomiting, diarrhea), bone marrow suppression leading to cytopenias, muscle weakness, peripheral neuropathy, and multi-organ failure in severe cases. Patients with renal or hepatic impairment are at particularly high risk. The interaction is clinically significant and can occur even with standard colchicine doses when combined with diltiazem.

Management and Precautions

When concurrent use is necessary, colchicine dose reduction is essential. For gout flares, reduce colchicine dose by 50% and monitor closely for toxicity symptoms. For gout prophylaxis, consider reducing the dose to 0.3mg daily or every other day. Regular monitoring should include complete blood count, liver function tests, and renal function. Patients should be educated about early signs of colchicine toxicity and advised to seek immediate medical attention if symptoms occur. Alternative treatments should be considered when possible, such as using different calcium channel blockers with less CYP3A4 inhibition or alternative gout medications.

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.

Diltiazem interactions with food and lifestyle

Grapefruit and grapefruit juice should be avoided while taking diltiazem 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 the blood pressure-lowering effects of diltiazem and increase the risk of dizziness, fainting, and falls. Patients should also be cautious when standing up quickly or engaging in activities requiring alertness, as diltiazem can cause dizziness and lightheadedness, especially when starting treatment or increasing the dose.