Summary

Pravastatin and cyclosporine have a clinically significant drug interaction where cyclosporine increases pravastatin blood levels, potentially leading to muscle toxicity. This interaction requires careful monitoring and possible dose adjustments to prevent serious adverse effects.

Introduction

Pravastatin is an HMG-CoA reductase inhibitor (statin) commonly prescribed to lower cholesterol and reduce cardiovascular risk. Cyclosporine is a potent immunosuppressive medication primarily used to prevent organ transplant rejection and treat certain autoimmune conditions. Both medications are frequently prescribed in clinical practice, making their potential interaction clinically relevant for healthcare providers and patients.

Mechanism of Interaction

The interaction between pravastatin and cyclosporine occurs through inhibition of hepatic uptake transporters, particularly OATP1B1 (organic anion transporting polypeptide 1B1). Cyclosporine inhibits these transporters, which are responsible for pravastatin uptake into hepatocytes. This inhibition leads to increased systemic exposure to pravastatin, with plasma concentrations potentially increasing 5-10 fold. Additionally, cyclosporine may interfere with pravastatin's biliary elimination, further contributing to elevated statin levels.

Risks and Symptoms

The primary risk of this interaction is increased pravastatin exposure leading to dose-dependent adverse effects, particularly muscle toxicity. Patients may experience myalgia (muscle pain), myopathy (muscle weakness), and in severe cases, rhabdomyolysis (muscle breakdown) which can cause kidney damage. The risk is dose-dependent and may be higher in elderly patients, those with kidney disease, or patients taking multiple medications. Elevated liver enzymes may also occur, though this is less common with pravastatin compared to other statins.

Management and Precautions

When pravastatin and cyclosporine must be used together, start with the lowest effective pravastatin dose (typically 10-20 mg daily) and avoid exceeding 20 mg daily. Monitor patients closely for signs of muscle toxicity including unexplained muscle pain, weakness, or dark urine. Baseline and periodic monitoring of creatine kinase (CK) levels and liver function tests is recommended. Educate patients about symptoms to report immediately. Consider alternative statins with less interaction potential if clinically appropriate, though all statins have some degree of interaction with cyclosporine. Regular follow-up appointments are essential for ongoing safety assessment.

Pravastatin interactions with food and lifestyle

Pravastatin should be taken with caution when consuming large amounts of grapefruit juice, though the interaction is less significant compared to other statins. While pravastatin is less affected by grapefruit juice than other statins like simvastatin or atorvastatin, patients should still limit excessive grapefruit juice consumption. Alcohol should be used with caution as both pravastatin and excessive alcohol can affect liver function, and combining them may increase the risk of liver problems. Patients should maintain consistent dietary habits and avoid excessive alcohol consumption while taking pravastatin.

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.