Pravastatin with Fenofibrate Interaction Details

Brand Names Associated with Pravastatin

Brand Names Associated with Fenofibrate

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

Interaction Effect

An increased risk of myopathy or rhabdomyolysis

Interaction Summary

The use of fibrate monotherapy may occasionally be associated with myositis, myopathy, or rhabdomyolysis. In numerous case reports where marked pharmacokinetic interactions were absent, the concomitant use of fibric acid derivatives and HMG-CoA reductase inhibitors has been associated with rhabdomyolysis, markedly elevated creatine kinase (CK) levels, and myoglobinuria, leading to a high frequency of acute renal failure. Therefore, the concomitant use of fenofibrate and HMG-CoA reductase inhibitors, including pravastatin, should generally be avoided unless the potential benefit from further lipid level adjustments outweighs the increased risk. If concurrent therapy is deemed necessary, monitor the patient for signs and symptoms of myositis, myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness), and discontinue use if creatine kinase (CK) levels show a marked increase, or if myopathy or rhabdomyolysis is diagnosed or suspected .

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concomitant use of fenofibrate and HMG-CoA reductase inhibitors, including pravastatin, should generally be avoided unless the potential benefit from further lipid level adjustments outweighs the increased risk. If concurrent therapy is deemed necessary, monitor the patient for signs and symptoms of myositis, myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness), and discontinue use if creatine kinase (CK) levels show a marked increase, or if myopathy or rhabdomyolysis is diagnosed or suspected .

Mechanism Of Interaction

Additive risk of myopathy

Literature Reports

A) Sixteen males and seven females, all Caucasian, participated in a single-dose, nonfasting, open-label, randomized, three-period crossover single-center study to focus on the possible pharmacokinetic changes of fenofibric acid, pravastatin, and 3,alpha-hydroxy-iso-pravastatin (3a-iso-pv) during pravastatin and fenofibrate coadministration. Study subjects received fenofibrate 201 mg alone, pravastatin 40 mg alone, or fenofibrate 201 mg plus pravastatin 40 mg. Concurrent administration of fenofibrate and pravastatin did not affect the pharmacokinetics of either fenofibric acid or pravastatin. However, the mean values of 3a-iso-pv Cmax and AUC were increased by 29% and 26%, respectively, with the coadministration of fenofibrate. 3a-iso-pv is approximately 2.5% to 10% as potent as pravastatin in HMG-CoA reductase inhibition, and the 26% increase in 3a-iso-pv Cmax would be expected to cause only a 0.65% to 2.6% increase in total pravastatin-related HMG-CoA reductase inhibitory activity. The authors concluded that it would be unlikely that the change in the 3a-iso-pv concentration would lead to any substantial pharmacological or toxicological outcome .

B) Pravastatin mean Cmax and AUC values increased by 36% (range from 69% decrease to 321% increase) and 28% (range from 54% decrease to 128% increase), respectively, following the concomitant administration of fenofibrate 145 mg and pravastatin 40 mg once daily for 10 days in 23 healthy adults. The 3,alpha-hydroxy-iso-pravastatin mean Cmax and AUC values increased by 55% (range from 32% decrease to 314% increase) and 39% (range from 24% decrease to 261% increase), respectively. The pharmacokinetics of fenofibric acid were not significantly altered .

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.

Fenofibrate Overview

• Fenofibrate is used with a low-fat diet, exercise, and sometimes with other medications to reduce the amounts of fatty substances such as cholesterol and triglycerides in the blood and to increase the amount of HDL (high-density lipoprotein; a type of fatty substance that decreases the risk of heart disease) in the blood. Build-up of cholesterol and fats along the walls of the arteries (a process known as atherosclerosis) decreases the blood flow and, therefore, the oxygen supply to the heart, brain, and other parts of the body. This increases the risk of heart disease, angina (chest pain), strokes, and heart attacks. Although fenofibrate decreases the levels of fatty substances in the blood, it has not been shown to decrease the risk of heart attacks or strokes. Fenofibrate is in a class of medications called antilipemic agents. It works by speeding the natural processes that remove cholesterol from the body.

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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.