Gemfibrozil with Atorvastatin Interaction Details

Brand Names Associated with Gemfibrozil

Brand Names Associated with Atorvastatin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 04, 2024

Interaction Effect

Increased atorvastatin exposure and an increased risk of myopathy or rhabdomyolysis

Interaction Summary

Coadministration of atorvastatin and gemfibrozil (an OATP1B1 transporter inhibitor) significantly increased the exposure of the atorvastatin metabolites[1], and clinically significant rhabdomyolysis has been reported in a case report of a patient treated concomitantly with both drugs [2]. Concomitant use of atorvastatin with gemfibrozil should be avoided [3]. due to an increased risk of myopathy/rhabdomyolysis [4][5].

Severity

Major

Onset

Delayed

Evidence

Established

How To Manage Interaction

Coadministration of atorvastatin (an OATP1B1 substrate) with gemfibrozil (an OATP1B1 inhibitor) significantly increased plasma levels of atorvastatin. Concomitant use of atorvastatin with gemfibrozil should be avoided due to an increased risk of myopathy/rhabdomyolysis[3][4].

Mechanism Of Interaction

Inhibition of OATP1B1-mediated atorvastatin transport by gemfibrozil

Literature Reports

A) Concomitant use of atorvastatin and gemfibrozil resulted in a significant increase in enantiomers of 2- and 4-hydroxy metabolites of atorvastatin related to gemfibrozil inhibition of the OATP1B1 transporter [1].

B) Subjects receiving a single dose of atorvastatin 40 mg who were coadministered gemfibrozil 600 mg twice daily for 7 days had a 35% increase in atorvastatin AUC [3].

C) Coadministration of single dose atorvastatin 40 mg with gemfibrozil 600 mg twice daily for 7 days led to a 1.35-fold increase in atorvastatin AUC and a 1-fold increase in Cmax [4].

D) Cases of myopathy/rhabdomyolysis have been reported with atorvastatin coadministered with lipid modifying doses (1 g/day or greater) of fibrates [4][6].

E) A study involving 10 healthy volunteers found gemfibrozil given 600 mg twice a day for 5 days and a single atorvastatin 20 mg dose on day 3 increased atorvastatin exposure when compared with atorvastatin plus placebo. Gemfibrozil raised the plasma concentrations of atorvastatin and of both the acid and lactone forms of the 2-hydroxy and 4-hydroxy metabolites, but had no effect on the concentration of atorvastatin lactone. The AUC of atorvastatin, 2-hydroxyatorvastatin acid, and 4-hydroxyatorvastatin acid increased 24%, 51% and 82% respectively. The respective lactone forms of the atorvastatin metabolites were increased by 29% and 28%. The maximum concentration (Cmax) of 2-hydroxyatorvastatin lactone increased by 36% and of 4-hydroxyatorvastatin acid by 173%. This was attributed to the possible inhibition of OATP1B1 - mediated hepatic uptake of atorvastatin and its hydroxylated metabolites [7].

F) A 43-year-old female with pancreatitis, chylomicronemia, dehydration, uncontrolled diabetes, a thrombotic diathesis, and arterial thromboses associated with foot ischemia was admitted to the hospital with a serum creatine kinase concentration of 4633 units/L. Prior to admission, she had been taking gemfibrozil 600 mg twice daily, cimetidine 400 mg twice daily, fluoxetine 20 mg once daily, medroxyprogesterone 10 mg twice daily, and furosemide on an as-needed basis. Three weeks before admission, atorvastatin 10 mg twice daily was added to her medication regimen. When no evidence of myocardial infarction or stroke was present, the atorvastatin and gemfibrozil were discontinued during the first day of her hospital stay. Her serum creatine kinase levels dropped steadily during the first two weeks, and continued to decrease when gemfibrozil was reinstituted on day 9. The rhabdomyolysis was attributed to an interaction between atorvastatin and gemfibrozil, and may have been potentiated by dehydration and pancreatitis [2].

References

1 ) Tornio A, Neuvonen PJ, Niemi M, et al: Role of gemfibrozil as an inhibitor of CYP2C8 and membrane transporters. Expert Opin Drug Metab Toxicol 2017; 13(1):83-95.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

2 ) Duell PB, Connor WE, & Illingworth DR: Rhabdomyolysis after taking atorvastatin with gemfibrozil. Am J Cardiol 1998; 81:368-369.

3 ) Product Information: LIPITOR(R) oral tablets, atorvastatin calcium oral tablets. Pfizer (Per FDA), New York, NY, 2012.

4 ) Product Information: ATORVALIQ(R) oral suspension, atorvastatin calcium oral suspension. CMP Pharma Inc (per FDA), Farmville, NC, 2023.

5 ) Product Information: LIPITOR(R) oral tablets, atorvastatin calcium oral tablets. Parke-Davis (per FDA), New York, NY, 2017.

6 ) Product Information: LIPITOR(R) oral tablets, atorvastatin calcium oral tablets. Parke-Davis (per FDA), New York, NY, 2020.

7 ) Backman J, Luurila H, Neuvonen M, et al: Rifampin markedly decreases and gemfibrozil increases the plasma concentrations of atorvastatin and its metabolites. Clin Pharmacol Ther 2005; 78:154-167.

Gemfibrozil Overview

• Gemfibrozil is used with diet changes (restriction of cholesterol and fat intake) to reduce the amount of cholesterol and triglycerides (other fatty substances) in the blood in certain people with very high triglycerides who are at risk of pancreatic disease (conditions affecting the pancreas, a gland that produces fluid to break down food and hormones to control blood sugar). Gemfibrozil is also used in people with a combination of low high-density lipoprotein (HDL; 'good cholesterol') levels and high low-density lipoprotein (LDL; 'bad cholesterol') and triglyceride levels to reduce the risk of heart disease. Gemfibrozil is in a class of lipid-regulating medications called fibrates. It works by reducing the production of triglycerides in the liver.

Atorvastatin Overview

• Atorvastatin 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. Atorvastatin is also used to decrease 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. Atorvastatin may also be used to decrease the amount of cholesterol and other fatty substances in the blood in children and teenagers 10 to 17 years of age who have familial heterozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Atorvastatin 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 atorvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.

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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.