Pravastatin with Nefazodone Interaction Details

Brand Names Associated with Pravastatin

Brand Names Associated with Nefazodone

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

Interaction Effect

An increased risk of myopathy or rhabdomyolysis

Interaction Summary

An elderly male experienced a total plasma creatine kinase (CK) concentration of 877 U/L (normal 0-190 U/L) when nefazodone was added to pravastatin therapy. Other liver function tests were also elevated. Discontinuing nefazodone returned his lab values to normal. It is possible that this patient's skeletal muscle toxicity was a result of nefazodone inhibiting the portion of pravastatin metabolism that is catalyzed by cytochrome P450 3A4. However, it should be noted that the patient was asymptomatic and his CK elevation did not reach the qualification for myopathy, which is defined as myalgia with CK concentrations more than 10 times the upper limit of normal .

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

If concurrent therapy is required, 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 cytochrome P450 3A4-mediated pravastatin metabolism by nefazodone

Literature Reports

A) A 74-year-old male was started on nefazodone 50 mg twice daily for a major depressive episode. Other medications included atenolol 100 mg daily, aspirin 100 mg daily, and pravastatin 20 mg daily. Because of the potential for a drug interaction between nefazodone and pravastatin, the total plasma creatine kinase (CK) was measured 36 hours after nefazodone was introduced. Results showed a CK level of 877 U/L (normal 0-190 U/L). Other abnormal laboratory values included lactate dehydrogenase 307 U/L (normal 115-200 U/L), aspartate aminotransferase 58 U/L (normal 0-30 U/L), and alanine aminotransferase 64 U/L (normal 0-30 U/L). The fractionation of the plasma CK showed that the proportion of CK-MB was only 1%, which suggested that the elevated CK had a skeletal muscle origin. Nefazodone was discontinued, and 14 days later the CK remained mildly elevated at 275 U/L. Pravastatin therapy was then discontinued, and the CK dropped to 169 U/L within three days. Pravastatin was reintroduced two weeks later, and lab values which were previously elevated remained within their therapeutic ranges .

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.

Nefazodone Overview

• Nefazodone is used to treat depression. Nefazodone is in a class of medications called serotonin modulators. It works by increasing the amounts of certain natural substances in the brain that are needed to maintain mental balance.

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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.