Summary

Rosuvastatin and cyclosporine have a clinically significant drug interaction that can lead to substantially increased rosuvastatin blood levels. This interaction increases the risk of statin-related muscle toxicity, including potentially serious conditions like rhabdomyolysis.

Introduction

Rosuvastatin is a potent HMG-CoA reductase inhibitor (statin) commonly prescribed to lower cholesterol and reduce cardiovascular risk. Cyclosporine is an 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 an important consideration for healthcare providers.

Mechanism of Interaction

The interaction between rosuvastatin and cyclosporine occurs primarily through inhibition of drug transporters. Cyclosporine inhibits OATP1B1 (organic anion transporting polypeptide 1B1), a hepatic uptake transporter responsible for rosuvastatin's uptake into liver cells. When this transporter is inhibited, rosuvastatin clearance is significantly reduced, leading to increased plasma concentrations. Studies have shown that cyclosporine can increase rosuvastatin exposure by up to 7-fold, making this one of the most significant pharmacokinetic interactions involving statins.

Risks and Symptoms

The primary clinical risk of this interaction is statin-induced muscle toxicity, ranging from mild myalgia to severe rhabdomyolysis. Elevated rosuvastatin levels increase the likelihood of muscle-related adverse effects, including muscle pain, weakness, and elevated creatine kinase levels. In severe cases, rhabdomyolysis can occur, potentially leading to acute kidney injury and other serious complications. Patients with additional risk factors such as advanced age, renal impairment, hypothyroidism, or concurrent use of other interacting medications may be at even higher risk for muscle toxicity.

Management and Precautions

When rosuvastatin and cyclosporine must be used together, careful dose adjustment and monitoring are essential. The recommended starting dose of rosuvastatin should not exceed 5 mg daily, with a maximum dose of 10 mg daily. Regular monitoring should include baseline and periodic creatine kinase levels, liver function tests, and assessment for muscle-related symptoms. Patients should be educated about signs and symptoms of muscle toxicity and advised to report muscle pain, weakness, or dark urine immediately. Alternative statin options with less interaction potential, such as pravastatin or fluvastatin, may be considered. Close collaboration between prescribing physicians is crucial to optimize both cardiovascular and immunosuppressive therapy while minimizing interaction risks.

Rosuvastatin interactions with food and lifestyle

Grapefruit and grapefruit juice should be avoided or consumed with caution while taking rosuvastatin, as they can increase blood levels of the medication and potentially increase the risk of side effects. Excessive alcohol consumption should be limited as it may increase the risk of liver problems when combined with rosuvastatin. Patients should maintain consistent dietary habits and inform their healthcare provider about any significant changes in diet or lifestyle.

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.