Lovastatin with Gemfibrozil Interaction Details
Brand Names Associated with Lovastatin
- Altocor®
- Altoprev®
- Lovastatin
- Mevacor®
Brand Names Associated with Gemfibrozil
- Gemfibrozil
- Lopid®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 25, 2023
Interaction Effect
Increased exposure of lovastatin acid (active metabolite) and an increased risk of myopathy or rhabdomyolysis
Interaction Summary
Concomitant use of lovastatin and gemfibrozil (an OATP1B1 transporter inhibitor) has resulted in an increase in the AUC of lovastatin acid (active metabolite) and concomitant use should be avoided . In several case reports, the concurrent use of lovastatin and gemfibrozil has resulted in severe myopathy and rhabdomyolysis .
Severity
Major
Onset
Delayed
Evidence
Established
How To Manage Interaction
The concomitant use of gemfibrozil and lovastatin should be avoided due to an increased risk of myopathy or rhabdomyolysis.
Mechanism Of Interaction
Inhibition of OATP1B1-mediated lovastatin transport by gemfibrozil
Literature Reports
A) Concomitant use of lovastatin and gemfibrozil (an OATP1B1 transporter inhibitor) resulted in a 2.8-fold increase in the AUC of lovastatin acid (active metabolite) .
B) Concomitant administration of gemfibrozil 600 mg twice daily for 3 days with lovastatin 40 mg daily in 11 subjects resulted in an AUC ratio (with concomitant lovastatin/without concomitant lovastatin) for lovastatin of 0.96 and lovastatin acid of 2.8 .
C) The Food and Drug Administration received 12 case reports of severe myopathy or rhabdomyolysis associated with concomitant use of lovastatin and gemfibrozil . All patients' serum creatine kinase levels rose to more than 10,000 International Units/L. Symptoms resolved when both drugs were discontinued. Because of the potential for severe myopathy or rhabdomyolysis, and because of the availability of alternative drug combinations for treating hyperlipidemia, the use of lovastatin in combination with gemfibrozil is discouraged.
D) The results of a prospective clinical trial in which 12 patients with heterozygous familial hypercholesterolemia were treated with the combination of lovastatin 80 mg daily and gemfibrozil 1200 mg daily indicated an increased risk of myopathy with this regimen. One patient developed an asymptomatic increase in creatine kinase (CK) with lovastatin monotherapy; however, the patient developed symptomatic myopathy (CK of 7840 Units/L) on the combination regimen, but recovered when the medications were withdrawn .
E) In a retrospective review, the authors concluded that the combination of lovastatin and gemfibrozil is safe in patients with normal renal function when the dose of lovastatin is carefully titrated and limited, and the CK and liver function tests are closely monitored. The researchers reviewed records for 70 patients (none had significant renal dysfunction) treated with a combination of lovastatin and gemfibrozil and determined that five patients had experienced mild CK elevations, one had a mild alanine aminotransferase (ALT) elevation, and one had both. However, there were no reports of muscle pain and/or weakness .
F) Researchers at the Cholesterol Center, Jewish Hospital of Cincinnati conducted two separate retrospective studies of their patients. In the first, the records of 25 patients with primary hyperlipoproteinemias who had undergone an average of 12.5 months of combination therapy with gemfibrozil and lovastatin indicated no myalgias, myositis, muscle weakness or tenderness in any patient . In the second retrospective study, the researchers reviewed records of 80 patients with primary mixed hyperlipidemia. The patients underwent at least six months of combination lovastatin/gemfibrozil treatment. They found no significant difference in the percentage of high CK levels per patient taking combination therapy verses lovastatin monotherapy. Three patients discontinued the regimen because of muscle symptoms or elevated CPK attributed to drug therapy; however, no patients experienced rhabdomyolysis, myoglobinuria, or renal failure .
G) A muscle biopsy performed as part of another case study confirmed the absence of inflammatory cells in a 57-year-old woman experiencing weakness after adding gemfibrozil to her drug regimen which included lovastatin. The author speculated that an immune-mediated mechanism is not the cause of the myopathy/rhabdomyolysis .
H) Gemfibrozil markedly increases the plasma concentrations of lovastatin acid resulting in an increased risk of developing myopathy. In addition, the resulting myopathy may be of pharmacokinetic origin. Eleven volunteers were included in a randomized, placebo-controlled, crossover, 3-phase study design. A two-week washout period separated the phases. Bezafibrate 400 mg slow release given once daily, gemfibrozil 600 mg twice daily, or placebo for 3 days. Lovastatin 40 mg was administered on day 4. During the gemfibrozil phase, the mean AUC (0-24) of lovastatin acid was 280% (p less than 0.001) and the maximum plasma concentration (Cmax) was 280% (p less than 0.05) of the values in the placebo phase. Gemfibrozil had no significant effects on the AUC (0-24) or Cmax of lovastatin. The AUC (0-24) ratio of lovastatin acid to lovastatin during the gemfibrozil phase was 3.2 times as high as the values in the placebo phase. Bezafibrate 400 mg had no marked effects on any of the pharmacokinetic variables of lovastatin or lovastatin acid. The results of this study demonstrate that gemfibrozil increases the plasma levels of active lovastatin acid without affecting the levels of parent lovastatin. Gemfibrozil increased the AUC and Cmax of lovastatin acid approximately 3-fold. The author concludes that the risk of developing myopathy may be smaller with bezafibrate as compared to gemfibrozil .
Lovastatin Overview
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Lovastatin 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. Lovastatin is also used to decrease the amount of cholesterol (a fat-like substance) and other fatty substances in the blood. Lovastatin 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.
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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 lovastatin may help prevent heart disease, angina (chest pain), strokes, and heart attacks.
Gemfibrozil Overview
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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.
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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:
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.