Summary

Pravastatin and cyclosporine have a clinically significant drug interaction where cyclosporine increases pravastatin blood levels, potentially leading to enhanced statin-related side effects including muscle toxicity. This interaction requires careful monitoring and possible dose adjustments when these medications are used together.

Introduction

Pravastatin is an HMG-CoA reductase inhibitor (statin) commonly prescribed to lower cholesterol levels and reduce cardiovascular risk. It works by blocking cholesterol synthesis in the liver and is generally considered one of the safer statins with fewer drug interactions. Cyclosporine is a potent immunosuppressive medication primarily used to prevent organ transplant rejection and treat certain autoimmune conditions. It belongs to the calcineurin inhibitor class and works by suppressing T-cell activation and immune responses.

Mechanism of Interaction

The interaction between pravastatin and cyclosporine occurs through multiple mechanisms. Cyclosporine inhibits organic anion transporting polypeptides (OATPs), particularly OATP1B1 and OATP1B3, which are responsible for the hepatic uptake of pravastatin. This inhibition reduces pravastatin clearance from the blood, leading to increased systemic exposure. Additionally, cyclosporine may interfere with pravastatin's biliary excretion and potentially affect other transport proteins involved in statin elimination, resulting in elevated pravastatin plasma concentrations that can be 5-10 times higher than normal.

Risks and Symptoms

The primary clinical risk of this interaction is an increased likelihood of statin-induced myopathy, including muscle pain, weakness, and in severe cases, rhabdomyolysis. Elevated pravastatin levels can also increase the risk of hepatotoxicity, though this is less common. Patients may experience muscle-related adverse effects at lower pravastatin doses than would typically cause problems. The risk is particularly concerning in patients with additional risk factors such as advanced age, renal impairment, hypothyroidism, or concurrent use of other medications that can cause muscle toxicity. Rhabdomyolysis, while rare, can lead to acute kidney injury and potentially life-threatening complications.

Management and Precautions

When pravastatin and cyclosporine must be used together, several management strategies should be implemented. Start with the lowest effective dose of pravastatin (typically 10-20 mg daily) and avoid exceeding 20 mg daily. Monitor patients closely for signs and symptoms of myopathy, including muscle pain, tenderness, or weakness. Baseline and periodic monitoring of creatine kinase (CK) levels and liver function tests is recommended. Educate patients about the signs of muscle toxicity and advise them to report any unexplained muscle symptoms immediately. Consider alternative statin options with lower interaction potential if clinically appropriate. Regular follow-up appointments should be scheduled to assess both efficacy and safety of the combination therapy.

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.