Gemfibrozil with Pravastatin Interaction Details
Brand Names Associated with Gemfibrozil
- Gemfibrozil
- Lopid®
Brand Names Associated with Pravastatin
- Pravachol®
- Pravastatin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 25, 2023
Interaction Effect
Decreased pravastatin clearance, increased pravastatin exposure, and increased risk of myopathy or rhabdomyolysis
Interaction Summary
Concomitant use of pravastatin and gemfibrozil (an OATP1B1 and OAT3 transporter inhibitor) has resulted in an increase in the exposure and a decrease in the clearance of pravastatin. The use of fibrates alone may occasionally be associated with the development of myopathy. Therefore, the combined use of pravastatin and gemfibrozil should be avoided. Carefully weigh the benefit/risk ratio of concurrent therapy. If coadministered, monitor the patient for signs and symptoms of myopathy or rhabdomyolysis, and discontinue use if CK levels show a marked increase, or if myopathy or rhabdomyolysis is diagnosed or suspected . However, one short-term study and one small, longer-term study found no rhabdomyolysis with this drug combination .
Severity
Major
Onset
Delayed
Evidence
Established
How To Manage Interaction
The concurrent use of gemfibrozil and pravastatin should be avoided. If concurrent therapy is required, monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness), and discontinue use if CK levels show a marked increase, or if myopathy or rhabdomyolysis is diagnosed or suspected.
Mechanism Of Interaction
Inhibition of OATP1B1- and OAT3-mediated pravastatin transport by gemfibrozil
Literature Reports
A) Concomitant use of pravastatin and gemfibrozil (an OATP1B1 and OAT3 transporter inhibitor) resulted in a 2-fold increase in the AUC of pravastatin .
B) Myopathy was not reported in a study involving the concurrent use of pravastatin 40 mg daily and gemfibrozil 1200 mg daily. However, 4 of the 75 subjects had markedly increased creatine phosphokinase (CPK) levels, compared to 1 of 73 subjects who received placebo. There were more frequent CPK elevations and patient withdrawals because of musculoskeletal symptoms in the groups receiving combination therapy than in the groups which received placebo or monotherapy with gemfibrozil or pravastatin .
C) A study of pravastatin and gemfibrozil cotherapy followed 32 hyperlipidemic patients for a year on average . No cases of myalgia or significant rises in liver enzymes (greater than 3 times normal) occurred. One case of asymptomatic elevation of creatine kinase was reported.
D) A double-blind, randomized, placebo-controlled study (n=290) of a combination regimen of pravastatin 40 mg with gemfibrozil 600 mg was compared to each drug alone and placebo. Researchers found no severe myopathy or rhabdomyolysis after 12 weeks. Severe myopathy was defined in this study as creatine kinase (CK) greater than 10,000 international units/L plus muscle pain and weakness. However, 2 patients on the combination regimen were removed from the study due to asymptomatic increased CK levels. In addition, 14 patients experienced musculoskeletal pain, most of which the investigators judged to be unrelated to the treatment, although one patient also had an increased CK level (950 international units/L). The mean AST level increased significantly from baseline in patients receiving the combination and gemfibrozil-only regimens. It is speculated that the hydrophilic properties of pravastatin may explain the drug's low incidence of myopathy. The drug is more selective for hepatocytes than other tissues. This study does not rule out myopathy after long-term treatment and therefore, advice is against the routine combination therapy with pravastatin and gemfibrozil .
E) An increase in pravastatin AUC occurs with concomitant gemfibrozil administration. A randomized, placebo-controlled, crossover study with 2 phases was used to evaluate the effect of concomitant gemfibrozil administration on the AUC of pravastatin. Subjects took gemfibrozil 600 mg or placebo for 3 days. On day 3, pravastatin 40 mg was administered. Gemfibrozil increased the plasma concentrations of pravastatin, as compared with placebo. In the gemfibrozil phase, the AUC (0-24) of pravastatin was 202% (range, 40% to 413%; p less than 0.05) and the Cmax was 181% (range, 27% to 428%; p less than 0.05) of the corresponding value in the placebo phase. The mean renal clearance of pravastatin was reduced from 25 L/hr to 14 L/hr (p less than 0.0001) by gemfibrozil. There was a significant correlation between the increase in AUC (0-24) of pravastatin and the decrease in its renal clearance caused by gemfibrozil (Pearson correlation coefficient, r equal to 0.72; p=0.02). The change in renal clearance was only a minor contributor to the increase in pravastatin AUC. Interference with a transport protein may contribute to the increase in pravastatin AUC from 0 hours to infinity by gemfibrozil. Reduced renal clearance of pravastatin is also a contributing factor .
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.
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.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
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.