Summary

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

Introduction

Rosuvastatin is a potent HMG-CoA reductase inhibitor (statin) commonly prescribed to lower cholesterol and reduce cardiovascular risk. It belongs to the class of lipid-lowering medications that work by blocking cholesterol synthesis in the liver. Cyclosporine is a calcineurin inhibitor immunosuppressant medication primarily used to prevent organ transplant rejection and treat certain autoimmune conditions. It works by suppressing T-cell activation and is considered a cornerstone therapy in transplant medicine and select rheumatologic disorders.

Mechanism of Interaction

The interaction between rosuvastatin and cyclosporine occurs through multiple pharmacokinetic pathways. Cyclosporine is a potent inhibitor of organic anion transporting polypeptides (OATP1B1 and OATP1B3), which are responsible for the hepatic uptake of rosuvastatin. When these transporters are inhibited, rosuvastatin clearance is significantly reduced, leading to substantially elevated plasma concentrations. Additionally, cyclosporine may inhibit P-glycoprotein and other efflux pumps, further contributing to increased rosuvastatin exposure. Studies have shown that cyclosporine can increase rosuvastatin AUC by 7-fold or more, representing one of the most significant pharmacokinetic drug interactions with statins.

Risks and Symptoms

The primary clinical risk of this interaction is severe muscle toxicity, ranging from myalgia and myopathy to potentially fatal rhabdomyolysis. The dramatically increased rosuvastatin levels can lead to muscle cell damage, elevated creatine kinase levels, and in severe cases, acute kidney injury secondary to myoglobin release. Patients may experience muscle pain, weakness, tenderness, and dark-colored urine. The risk is particularly elevated in patients with additional risk factors such as advanced age, renal impairment, hypothyroidism, or concurrent use of other medications that increase statin toxicity risk. This interaction is considered contraindicated or requires extreme caution with significant dose reduction.

Management and Precautions

Management of this interaction requires careful consideration of the risk-benefit ratio. If both medications are absolutely necessary, rosuvastatin should be initiated at the lowest possible dose (typically 5mg daily or less) with close monitoring for signs of muscle toxicity. Regular monitoring should include baseline and periodic creatine kinase levels, liver function tests, and clinical assessment for muscle symptoms. Patients should be educated about the signs and symptoms of muscle toxicity and instructed to report any muscle pain, weakness, or dark urine immediately. Alternative statin options with lower interaction potential, such as pravastatin or fluvastatin, should be strongly considered. In many cases, the combination may be contraindicated, and alternative lipid-lowering strategies should be explored. Healthcare providers should consult current prescribing information and consider specialist consultation when managing this complex interaction.

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.