Summary

Diltiazem significantly increases cyclosporine blood levels by inhibiting its metabolism, potentially leading to cyclosporine toxicity. This interaction requires careful monitoring and possible dose adjustments when these medications are used together.

Introduction

Cyclosporine is a potent immunosuppressive medication primarily used to prevent organ transplant rejection and treat certain autoimmune conditions like rheumatoid arthritis and psoriasis. It belongs to the calcineurin inhibitor class of drugs. Diltiazem is a calcium channel blocker commonly prescribed for treating high blood pressure, angina, and certain heart rhythm disorders. It works by relaxing blood vessels and reducing the heart's workload.

Mechanism of Interaction

Diltiazem inhibits the cytochrome P450 3A4 (CYP3A4) enzyme system, which is the primary pathway for cyclosporine metabolism in the liver. When diltiazem blocks this enzyme, cyclosporine clearance is significantly reduced, leading to increased cyclosporine blood concentrations. This pharmacokinetic interaction can result in cyclosporine levels that are 2-3 times higher than expected, potentially reaching toxic levels.

Risks and Symptoms

The primary risk of this interaction is cyclosporine toxicity, which can manifest as nephrotoxicity (kidney damage), hepatotoxicity (liver damage), neurotoxicity (tremors, seizures, confusion), hypertension, and increased susceptibility to infections and malignancies due to over-immunosuppression. Patients may experience symptoms such as decreased kidney function, elevated liver enzymes, tremors, headaches, and increased blood pressure. The interaction is considered clinically significant and requires immediate attention.

Management and Precautions

When cyclosporine and diltiazem must be used together, close monitoring is essential. Cyclosporine blood levels should be checked more frequently, typically within 3-5 days of starting diltiazem and then weekly until stable. A cyclosporine dose reduction of 25-50% may be necessary when initiating diltiazem therapy. Kidney function (serum creatinine, BUN), liver function tests, and blood pressure should be monitored regularly. Consider alternative antihypertensive agents like ACE inhibitors or ARBs if possible. If diltiazem is discontinued, cyclosporine levels may drop significantly, requiring dose increases and continued monitoring.

Cyclosporine interactions with food and lifestyle

Cyclosporine has several important food and lifestyle interactions that patients should be aware of: **Grapefruit and Grapefruit Juice:** Avoid grapefruit and grapefruit juice while taking cyclosporine. Grapefruit contains compounds that inhibit CYP3A4 enzymes, which can significantly increase cyclosporine blood levels and potentially lead to toxicity. This interaction is well-documented and patients are specifically warned to avoid grapefruit products. **High-Fat Meals:** Taking cyclosporine with high-fat meals can increase the absorption of the medication, potentially leading to higher blood levels. While this doesn't require complete avoidance, patients should maintain consistent dietary habits and take cyclosporine at the same time each day relative to meals. **St. John's Wort:** This herbal supplement should be avoided as it can significantly decrease cyclosporine blood levels by inducing CYP3A4 enzymes, potentially leading to organ rejection in transplant patients or treatment failure. **Alcohol:** While moderate alcohol consumption may not be completely contraindicated, patients should discuss alcohol use with their healthcare provider as cyclosporine can affect liver function, and alcohol may compound these effects. **Sun Exposure:** Patients taking cyclosporine have an increased risk of skin cancer and should limit sun exposure, use sunscreen with high SPF, and wear protective clothing when outdoors.

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.