Pravastatin with Cyclosporine Interaction Details

Brand Names Associated with Pravastatin

Brand Names Associated with Cyclosporine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 11, 2023

Interaction Effect

Increased pravastatin exposure and an increased risk of myopathy or rhabdomyolysis

Interaction Summary

Studies comparing concurrent use of pravastatin and cycloSPORINE with pravastatin alone indicates that concurrent use results in significantly higher levels of pravastatin; however, 4 other studies found no association with rhabdomyolysis . Due to the potential increased risk of myopathy and rhabdomyolysis with pravastatin and cycloSPORINE combination therapy, initiate pravastatin at 10 mg once daily at bedtime and titrate cautiously to a maximum of 20 mg/day . Monitoring is recommended if concomitant use is required .

Severity

Major

Onset

Rapid

Evidence

Probable

How To Manage Interaction

Concomitant use of cycloSPORINE and pravastatin should be undertaken with caution. If concomitant use is required, therapy should be initiated with pravastatin 10 mg once daily at bedtime. Titration of pravastatin to higher doses should be done cautiously, with daily doses not exceeding 20 mg. Monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness). Monitor creatine kinase (CK) levels and discontinue use if CK levels show a marked increase, or if myopathy or rhabdomyolysis is diagnosed or suspected.

Mechanism Of Interaction

Inhibition of pravastatin metabolism

Literature Reports

A) In drug interaction studies, the concomitant administration of cycloSPORINE and pravastatin resulted in an increase in pravastatin AUC and Cmax. Patients received single doses of cycloSPORINE 5 mg/kg and pravastatin 40 mg. Comparing cycloSPORINE plus pravastatin versus pravastatin administration alone, there was a 282% and 327% increase in pravastatin AUC and Cmax, respectively .

B) The concurrent use of single-dose pravastatin and cycloSPORINE was studied in 10 cardiac transplant patients and 10 non-transplant, hypercholesteremic patients. The 2 groups were not age or sex matched. The patients in the transplant group were receiving enough cycloSPORINE to maintain a plasma level of 80 to 360 nanograms/milliliter, prednisone, and azathioprine. Both groups were given pravastatin 20 mg orally after an overnight fast, which was continued for at least an hour after pravastatin administration. In the transplant group, the pravastatin Cmax value was 7 times greater, the AUC values were significantly higher, and the half-life was 4 times longer than for the nontransplant group. Because both pravastatin and cycloSPORINE are metabolized by the liver, it is likely that cycloSPORINE inhibits pravastatin metabolism .

C) A follow-up study after 4 years of a pravastatin 10-mg/day regimen in 24 renal transplant patients also treated with cycloSPORINE found no association with rhabdomyolysis. There was no increase in serum CPK levels throughout the treatment, and, although AST and ALT levels were increased in 2 patients, discontinuation of treatment was not required. The authors speculate that since pravastatin is water soluble, it may not enter muscle cells to interfere with cholesterol synthesis there .

D) In another study, 31 renal transplant patients taking pravastatin 20 mg daily for a minimum of 12 months along with cycloSPORINE and prednisone to maintain immunosuppression showed no adverse effects associated with rhabdomyolysis or myopathy. Only 2 patients experienced any adverse effects: 1 patient with nausea and vomiting who left the study after 3 doses of pravastatin and another patient with increased ALT, gamma-glutamyltranspeptidase (GGT), and alkaline phosphatase who was later diagnosed with gall bladder carcinoma. The pravastatin dose was increased to 30 mg daily in 4 patients after 3 months of treatment, due to continued high cholesterol. The authors conclude that pravastatin is safe to use in patients undergoing cycloSPORINE immunosuppression as long as the doses are moderate, and liver and renal function are monitored carefully .

E) Twenty-one renal transplant patients treated with cycloSPORINE received pravastatin 20 mg daily or lovastatin 20 mg daily for 28 days. Pharmacokinetic comparisons of single-dose (day 1) versus multiple-dose (day 28) pravastatin therapy indicated that since the AUC and Cmax were comparable on both occasions, pravastatin does not accumulate in the presence of cycloSPORINE. However, the authors point out that these AUC values are approximately 5 to 7 times higher than previously reported results in patients not receiving cycloSPORINE. Mean CPK, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and myoglobin were only minimally changed at day 28 compared with baseline values. The authors concluded that since cycloSPORINE had little impact on pravastatin pharmacokinetics, pravastatin may be useful in the long-term treatment of renal transplant patients taking cycloSPORINE .

F) Thirty-one renal transplant patients receiving cyclosporine therapy and having hypercholesterolemia and hypertriglyceridemia were entered into a study to determine the efficacy and safety of pravastatin and simvastatin. Fifteen patients were given simvastatin 10 mg once daily for 9 months while 16 patients received pravastatin 20 mg once daily for 9 months. Neither drug altered cycloSPORINE trough concentrations during the study, and significant changes in the cycloSPORINE dose were not needed. Additionally, clinical signs of myopathy and alterations in serum CPK were not observed .

G) One hundred and ten heart transplant recipients who had been treated with simvastatin 10 mg daily (n=26), simvastatin 20 mg daily (n=18), or pravastatin 20 mg daily (n=66) and immunosuppressive therapy consisting of cycloSPORINE, azathioprine, and prednisone were retrospectively studied. Four patients, all receiving simvastatin 20 mg daily, developed rhabdomyolysis, with a mean serum creatine kinase (CK) level of 2505 units/L. Two patients on pravastatin therapy showed mild, asymptomatic CK elevations (525 and 600 units/L) which returned to baseline after withdrawal of pravastatin .

Pravastatin Overview

• Pravastatin 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. Pravastatin is also used to reduce the amount of fatty substances such as low-density lipoprotein (LDL) cholesterol ('bad cholesterol') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol ('good cholesterol') in the blood. Pravastatin 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 pravastatin has been shown to 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.