Gemfibrozil with Fluvastatin Interaction Details

Brand Names Associated with Gemfibrozil

Brand Names Associated with Fluvastatin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 25, 2023

Interaction Effect

An increased risk of myopathy or rhabdomyolysis

Interaction Summary

Concurrent use of fluvastatin with gemfibrozil should be avoided due to an increased risk of myopathy and rhabdomyolysis. Several small studies have investigated the concomitant use of fluvastatin and gemfibrozil, and found no adverse effects on muscle tissue  nor any pharmacokinetic interactions, lending support to the clinical observations that the combination may be safe . However, the potential risks and benefits of combination therapy with fluvastatin and gemfibrozil should be carefully considered as rhabdomyolysis has been reported . In patients whose lipid response is inadequate with either drug alone, the increased risk of serious events associated with combination therapy appear to outweigh the potential benefits on lipid levels .

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Concomitant use of fluvastatin and gemfibrozil should be avoided, as this may lead to an increased risk of myopathy and/or rhabdomyolysis. The increased risk of severe myopathy, rhabdomyolysis, and acute renal failure associated with concurrent use of gemfibrozil plus an HMG-CoA reductase inhibitor appear to outweigh potential benefits on lipid levels .

Mechanism Of Interaction

Unknown

Literature Reports

A) In an open-label crossover pharmacokinetic study of 17 hyperlipidemic patients, researchers found no significant differences in the area under the concentration-time curve (AUC), maximum concentration (Cmax), or time to maximum concentration (Tmax) between fluvastatin 20 mg twice daily taken alone, gemfibrozil 600 mg twice daily taken alone, or the combination of the two drugs. There were no significant adverse effects noted. However, the authors point out that because of the small sample size, conclusions cannot be drawn about safety .

B) A 56-year-old female developed rhabdomyolysis one month after beginning therapy with fluvastatin 80 mg per day and gemfibrozil 1200 mg per day. The patient had a history of hyperlipidemia and was receiving no other drug therapy. She presented with fatigue, weakness in her legs, and red-colored urine. Her liver enzymes were elevated (alanine aminotransferase 2100 units/L, aspartate aminotransferase 2640 units/L) and her renal function tests revealed renal dysfunction (creatinine 1.84 mg/dL, BUN 58 mg/dL). Serum creatinine phosphokinase was 45,758 units/L (reference range 30-170), lactate dehydrogenase was 7169 units/L (230-460), and myoglobin was more than 3000 ng/mL (0-72). She was diagnosed with acute hepatocellular injury and acute renal failure secondary to rhabdomyolysis. All medications were withheld and her nutritional status and liver and kidney function test results returned to normal within two weeks. The author concludes that this patient's hepatocellular injury and rhabdomyolysis were associated with an interaction between fluvastatin and gemfibrozil. Potential risks and benefits should be considered and the patient should be advised of potential toxicities and side effects when fluvastatin and gemfibrozil are coadministered .

C) Fluvastatin and gemfibrozil, administered either as monotherapy or as combination therapy, did not induce muscle damage in 21 patients with combined hyperlipidemia in a 6-week, double-blind, placebo-controlled study. Subjects were randomized into three groups: fluvastatin 40 mg daily plus gemfibrozil placebo; gemfibrozil 600 mg twice daily plus fluvastatin placebo; or fluvastatin 40 mg daily plus gemfibrozil 600 mg twice daily. Muscle damage was assessed by means of a 45-minute exercise muscle-provocation test both before and after the six week treatment period, followed by a muscle needle biopsy from the quadriceps 48 hours after the exercise tests, as well as serum CPK and myoglobin samples. The authors found no significant difference between the pre- and post-treatment mean peak CPK rise with combination therapy or fluvastatin alone. The authors concluded that combination therapy has no adverse effects on muscle .

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.

Fluvastatin Overview

• Fluvastatin 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. Fluvastatin 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. Fluvastatin 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). Fluvastatin 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 fluvastatin 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.