Lovastatin with Cyclosporine Interaction Details

Brand Names Associated with Lovastatin

Brand Names Associated with Cyclosporine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 15, 2023

Interaction Effect

Increased lovastatin plasma levels and an increased risk of myopathy or rhabdomyolysis

Interaction Summary

Concomitant use of lovastatin and cycloSPORINE should be avoided as it has resulted in a 3- to 5-fold increase in the AUC of lovastatin in a study in stable kidney transplant patients. There have been reports of reversible myopathy (rhabdomyolysis) in small studies and case reports , while 2 small 6-month studies found that low-dose lovastatin (20 mg daily) combined with cycloSPORINE did not produce myopathy in stable renal transplant patients . Alternatively, consider switching to a statin such as fluvastatin, pravastatin, or rosuvastatin. Follow the individual product labeling dosage adjustment recommendation carefully and monitor creatine kinase and signs and symptoms of myalgia or rhabdomyolysis. Withhold or discontinue statin therapy when myopathy or rhabdomyolysis is suspected.

Severity

Major

Onset

Delayed

Evidence

Established

How To Manage Interaction

Concomitant use of lovastatin and cycloSPORINE should be avoided, as it has resulted in a 3- to 5-fold increase in the AUC of lovastatin in a study in stable kidney transplant patients. Alternatively, consider switching to a statin such as fluvastatin, pravastatin, or rosuvastatin. Follow the individual product labeling dosage adjustment recommendation carefully and monitor creatine kinase and signs and symptoms of myalgia or rhabdomyolysis. Withhold or discontinue statin therapy when myopathy or rhabdomyolysis is suspected.

Mechanism Of Interaction

Inhibition of CYP3A4-mediated lovastatin metabolism by cycloSPORINE

Literature Reports

A) In a study of cyclosporine-treated post kidney transplant patients with stable graft function, coadministration of lovastatin 10 mg daily for 10 days resulted in a 3- to 5-fold increase in the AUC of lovastatin .

B) Myositis and elevated creatine phosphokinase have been reported in less than 0.5% of patients receiving lovastatin alone. In patients receiving immunosuppressive therapy, including cycloSPORINE, myopathy occurred in up to 30% of patients within one year after lovastatin was added to therapy .

C) Rhabdomyolysis and acute renal failure were reported in a 48-year-old cardiac transplant patient who was later treated for hypercholesterolemia and hypertriglyceridemia . His drug regimen included cycloSPORINE 3 mg per kg per day, azathioprine 100 mg daily, prednisone 15 mg three times daily, gemfibrozil 300 mg three times daily, and lovastatin 40 mg daily. After 36 hours of combined therapy, the patient experienced muscular aches, weakness, and general malaise. Swollen, hyalinized, eosinophilic muscle fibers without inflammatory infiltrate were seen on muscle biopsy, and renal biopsy revealed widened necrotic tubules filled with eosinophilic, granular material identified as myoglobin. This condition was diagnosed as acute tubular necrosis with myoglobinuria. The hypolipidemic drugs were discontinued and hemodialysis was necessary. The patient recovered fully after four weeks.

D) Plasma levels of lovastatin were compared in five groups: 1) six heart transplant recipients receiving cycloSPORINE, prednisolone, and azathioprine, 2) five kidney transplant recipients receiving cycloSPORINE, prednisolone, and azathioprine, 3) five kidney recipients receiving azathioprine and prednisolone, 4) five patients with psoriasis receiving cycloSPORINE monotherapy, and 5) eight hypercholesterolemic control patients. All patients received lovastatin 10 mg once daily for ten days. By grouping all of the patients who were receiving cycloSPORINE, lovastatin increased the area under the concentration-time curve (AUC) from 0-8 hours to 152 ng/hr/mL, compared to 30 ng/hr/mL for patients not receiving cycloSPORINE. This study demonstrated that patients who receive cycloSPORINE as a single drug have similar lovastatin plasma levels as patients receiving triple drug regimens .

E) In a six-month clinical trial of 12 hyperlipidemic kidney graft recipients treated with cycloSPORINE, the addition of a daily dose of 20 mg lovastatin did not produce any evidence of myopathy. Creatine phosphokinase (CPK), liver enzymes, and cycloSPORINE levels remained stable throughout the treatment period, and there was no evidence of myopathy. No patients withdrew due to adverse side effects. The authors point out that in studies in which lovastatin treatment resulted in myopathy, the dose was higher than the 20 mg daily dose used in this trial; however, they do advise vigilance when using lovastatin concomitantly with cycloSPORINE .

F) Another study of hyperlipidemic renal transplant patients found that the addition of lovastatin 20 mg daily to their existing cycloSPORINE regimen did not produce changes in liver or muscle enzymes. The 12 patients, who were on a cycloSPORINE mean daily dose of 2.5 +/- 1.2 mg per kg, began a 6-month treatment period with lovastatin 20 mg daily after completing an initial 3-month diet/washout. Halfway through the treatment period, five patients were increased to lovastatin 30 mg daily due to inadequate response. Overall, some patients reported transient muscle pain, but CK and myoglobin laboratory results remained in the normal range throughout the study, as did the renal and hepatic function tests for all patients. Quantitative electromyography performed before and after the study was normal. The authors speculate that adverse events may have been avoided because of the low doses of both cycloSPORINE and lovastatin. Further, they point out that increasing the five inadequate responders' lovastatin dose to 30 mg daily did not produce further lipid-lowering benefit .

G) In two case studies, lovastatin and cycloSPORINE combination therapy was associated with the development of rhabdomyolysis in cardiac transplant patients. A 46-year old cardiac transplant patient developed muscle pain, elevated CK (peak at 23,832 units/L), and myoglobinuric acute renal failure after taking both cycloSPORINE (150 mg twice daily) and lovastatin 40 mg twice daily for 14 months. Two weeks before the development of muscle pain, the patient had been hospitalized for Legionella pneumonia, and had received erythromycin both in the hospital and after discharge. Lovastatin was temporarily discontinued, cycloSPORINE dosage reduced, and erythromycin discontinued. After the patient recovered, he was rechallenged with lovastatin 80 mg daily, and his CK levels were normal. In a second case, a 36-year old transplant patient was hospitalized with muscle aches and a CK of 8920 units/L nine months after lovastatin 80 mg daily was added to his regimen of cycloSPORINE 120 mg twice daily. The lovastatin metabolite level at that time was ten times the expected value. The patient recovered after the two drugs were discontinued. The authors speculate that both patients had liver impairment caused by elevated levels of cycloSPORINE which resulted in high lovastatin levels and rhabdomyolysis .

Lovastatin Overview

• Lovastatin is used together with diet, weight-loss, and exercise to reduce the risk of heart attack and stroke and to decrease the chance that heart surgery will be needed in people who have heart disease or who are at risk of developing heart disease. Lovastatin is also used to decrease the amount of cholesterol (a fat-like substance) and other fatty substances in the blood. Lovastatin is in a class of medications called HMG CoA reductase inhibitors (statins). It works by slowing the production of cholesterol in the body to decrease the amount of cholesterol that may build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.

• Accumulation of cholesterol and fats along the walls of your arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to your heart, brain, and other parts of your body. Lowering your blood level of cholesterol and fats with lovastatin may help prevent heart disease, angina (chest pain), strokes, and heart attacks.

Cyclosporine Overview

• Cyclosporine and cyclosporine (modified) are used with other medications to prevent transplant rejection (attack of the transplanted organ by the immune system of the person who received the organ) in people who have received kidney, liver, and heart transplants. Cyclosporine (modified) is also used alone or with methotrexate (Rheumatrex) to treat the symptoms of rheumatoid arthritis (arthritis caused by swelling of the lining of the joints) in patients whose symptoms were not relieved by methotrexate alone. Cyclosporine (modified) is also used to treat psoriasis (a skin disease in which red, scaly patches form on some areas of the body) in certain patients who have not been helped by other treatments. Cyclosporine and cyclosporine (modified) are in a class of medications called immunosuppressants. They work by decreasing the activity of the immune system.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.