Summary

Itraconazole significantly increases amlodipine blood levels by inhibiting the CYP3A4 enzyme responsible for amlodipine metabolism. This interaction can lead to enhanced hypotensive effects and increased risk of amlodipine-related side effects including severe hypotension and peripheral edema.

Introduction

Amlodipine is a long-acting calcium channel blocker commonly prescribed for hypertension and angina, belonging to the dihydropyridine class of medications. Itraconazole is a triazole antifungal medication used to treat various systemic and superficial fungal infections. Both medications are frequently prescribed, making awareness of their interaction clinically important for healthcare providers and patients.

Mechanism of Interaction

The interaction occurs through itraconazole's potent inhibition of the cytochrome P450 3A4 (CYP3A4) enzyme system. Amlodipine is primarily metabolized by CYP3A4 in the liver and intestines. When itraconazole blocks this metabolic pathway, amlodipine clearance is significantly reduced, leading to increased plasma concentrations and prolonged half-life. Studies have shown that itraconazole can increase amlodipine AUC (area under the curve) by up to 90% and maximum plasma concentration by approximately 60%.

Risks and Symptoms

The primary clinical risks include severe hypotension, which may lead to dizziness, fainting, or cardiovascular compromise, particularly in elderly patients or those with existing cardiovascular conditions. Patients may experience enhanced peripheral edema, flushing, and headaches due to increased calcium channel blockade. The interaction is considered clinically significant and may persist for several days after discontinuing itraconazole due to its long half-life and irreversible enzyme binding.

Management and Precautions

Close monitoring of blood pressure and cardiovascular status is essential when these medications are used concurrently. Consider reducing the amlodipine dose by 50% when initiating itraconazole therapy, with careful titration based on patient response. Monitor for signs of hypotension, edema, and other amlodipine-related adverse effects. Alternative antifungal agents with less CYP3A4 inhibition potential, such as fluconazole or terbinafine, may be considered when clinically appropriate. Patients should be counseled about potential symptoms and advised to report dizziness, swelling, or other concerning symptoms promptly.

Amlodipine interactions with food and lifestyle

Grapefruit and grapefruit juice should be avoided or consumed with caution while taking amlodipine, as they can increase blood levels of the medication and potentially lead to excessive blood pressure lowering and increased side effects. Alcohol consumption should be limited as it may enhance the blood pressure-lowering effects of amlodipine, potentially causing dizziness, lightheadedness, or fainting. Patients should be cautious when standing up quickly or engaging in activities requiring alertness, especially when starting treatment or adjusting doses.

Itraconazole interactions with food and lifestyle

Itraconazole should be taken with food to enhance absorption and bioavailability. The capsule formulation requires an acidic environment for optimal absorption, so it should be taken with a full meal or acidic beverage. Avoid taking itraconazole with antacids, H2 blockers, or proton pump inhibitors as these reduce stomach acid and significantly decrease drug absorption. Grapefruit juice should be avoided as it can increase itraconazole levels and risk of side effects. Alcohol should be used with caution as both itraconazole and alcohol can affect liver function.