Summary

Colchicine and indinavir have a significant drug interaction where indinavir can substantially increase colchicine blood levels, leading to potentially serious colchicine toxicity. This interaction requires careful monitoring and often dose adjustments or alternative treatments.

Introduction

Colchicine is an anti-inflammatory medication primarily used to treat and prevent gout attacks and familial Mediterranean fever. It works by inhibiting microtubule formation and reducing neutrophil migration. Indinavir is a protease inhibitor antiretroviral medication used in the treatment of HIV infection. It belongs to a class of drugs that block HIV protease enzyme, preventing viral replication.

Mechanism of Interaction

The interaction between colchicine and indinavir occurs through inhibition of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein transport systems. Indinavir is a potent inhibitor of both CYP3A4 enzyme and P-glycoprotein efflux pump, which are the primary pathways for colchicine metabolism and elimination. When indinavir blocks these pathways, colchicine clearance is significantly reduced, leading to increased plasma concentrations and prolonged half-life of colchicine.

Risks and Symptoms

The primary risk of this interaction is colchicine toxicity, which can manifest as severe gastrointestinal symptoms including nausea, vomiting, diarrhea, and abdominal pain. More serious complications can include bone marrow suppression, leading to neutropenia, thrombocytopenia, and anemia. Neuromuscular toxicity may also occur, presenting as muscle weakness or neuropathy. In severe cases, multi-organ failure and death have been reported. Patients with renal or hepatic impairment are at particularly high risk for severe toxicity.

Management and Precautions

When concurrent use is necessary, colchicine dosing must be significantly reduced. For gout flares, the maximum colchicine dose should not exceed 0.6 mg once daily for patients taking indinavir. For gout prophylaxis, doses should be reduced to 0.3 mg once daily or every other day. Patients should be closely monitored for signs of colchicine toxicity, including gastrointestinal symptoms and blood count abnormalities. Alternative gout treatments such as NSAIDs or corticosteroids should be considered when appropriate. Healthcare providers should verify current dosing recommendations and consider consultation with specialists when managing this interaction.

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.

Indinavir interactions with food and lifestyle

Indinavir should be taken on an empty stomach, at least 1 hour before or 2 hours after meals, for optimal absorption. However, if gastrointestinal upset occurs, it may be taken with a light meal that is low in fat, calories, and protein. High-fat meals can significantly reduce indinavir absorption and effectiveness. Patients should maintain adequate hydration by drinking at least 1.5 liters (approximately 6 glasses) of water daily to prevent kidney stone formation, a known side effect of indinavir. Grapefruit juice should be avoided as it may increase indinavir blood levels and potentially increase the risk of side effects. St. John's wort should be strictly avoided as it can significantly reduce indinavir blood levels and lead to treatment failure and potential development of drug resistance.