Gemfibrozil with Warfarin Interaction Details
Brand Names Associated with Gemfibrozil
- Gemfibrozil
- Lopid®
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 25, 2023
Interaction Effect
An increased risk of bleeding
Interaction Summary
Concomitant gemfibrozil and warfarin therapy has resulted in an increased hypoprothrombinemic response and bleeding, and therefore should be used with caution. If concomitant use is required, monitor prothrombin time frequently until levels stabilize and reduce warfarin dosage if necessary to maintain desired prothrombin time and to prevent bleeding . Monitor for both immediate- and delayed-onset bleeding with concomitant use of warfarin and fibrates .
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Concomitant use of gemfibrozil and warfarin may increase the risk of bleeding and should be used with caution. If concomitant use is required, monitor prothrombin time frequently until levels stabilize and reduce warfarin dosage if necessary to maintain desired prothrombin time and to prevent bleeding. Monitor for both immediate- and delayed-onset bleeding with concomitant use of warfarin and fibrates .
Mechanism Of Interaction
Additive effects on anticoagulation
Literature Reports
A) Coadministration of warfarin with gemfibrozil compared to warfarin with pravastatin was associated with a 79% increased risk of a composite of gastrointestinal bleeding (GIB) or intracranial hemorrhage (ICH) within the first 30 days of concomitant use (adjusted HR, 1.79; 1.36 to 2.35) in a propensity score-adjusted cohort study of users of warfarin and antihyperlipidemics (N=236,691; median age, 71 years; 63% women). The associated increased risk with gemfibrozil was most pronounced within the first 10 days of concomitant use (adjusted HR, 2.09; 1.35 to 3.24). Additionally, coadministration of warfarin with fenofibrate products was associated with an 80% increased risk of GIB/ICH during the second month of coadministration (days 30 to 59; adjusted HR, 1.8; 1.2 to 2.7); there was no significant difference in risk within the first 30 days of concomitant use. Antihyperlipidemics studied were fenofibrate (including fenofibric acid), gemfibrozil, or a statin (ie, atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin or simvastatin). Warfarin and individual statins (including pravastatin) did not show an increased risk of GIB/ICH .
B) Concurrent use of gemfibrozil and warfarin was associated with elevated INR values in a 46 year-old male. The patient was stable on warfarin 45 mg/week (target range, 2.0 to 3.0) for paroxysmal atrial fibrillation for the past 9 months. During routine follow-up at a anticoagulant clinic, the patient's INR value was supratherapeutic (5.8). The only change to the patient's drug regimen was the addition of gemfibrozil 600 mg twice daily 3 weeks earlier and he denied any changes in prescription, over-the-counter or herbal products as well as changes in diet. Laboratory testing revealed no other abnormalities. The patient's warfarin dose was reduced by 22% (35 to 37.5 mg/week) which maintained a therapeutic INR value. Four months later, gemfibrozil was discontinued due to myalgia, which led to subtherapeutic INRs (1.7 to 1.8). The warfarin dose was increased to 45 mg/week and the patient maintained appropriate therapeutic INR values. The Drug Interaction Probability Scale indicated a probable interaction. An empiric dosage reduction of 20% was suggested .
C) Gemfibrozil was reported to inhibit the metabolism of warfarin in a 38-year-old female. The patient was maintained on warfarin 5 mg for five months when gemfibrozil 1200 mg daily in divided doses was added. Two weeks after initiation of the gemfibrozil, the patient presented with prolonged menstrual bleeding with numerous blood clots. Her prothrombin time was also elevated. The warfarin dose was reduced to 2.5 mg daily. Menstrual bleeding was resolved two weeks after the dosage change. It was determined that the patient experienced severe bleeding due to the decreased metabolism of warfarin resulting from this drug interaction with gemfibrozil .
D) A 73-year-old male who had been stabilized on warfarin 5 mg alternating with 7.5 mg daily for the previous three years was admitted to the hospital after three days of fatigue, black stools, and a large bruise on his arm. Five weeks previously, he was started on gemfibrozil 1200 mg daily for hyperlipidemia. While his international normalized ratio (INR) had averaged 2.6 during his warfarin therapy, it was increased to 43 on admission, and the prothrombin time was measured at 66 seconds. Warfarin and gemfibrozil were both discontinued, and vitamin K 10 mg was administered. Three days later, warfarin therapy was again instituted without a change in dose with resulting therapeutic INRs and no evidence of bleeding .
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.
Warfarin Overview
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Warfarin is used to prevent blood clots from forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types of irregular heartbeat, people with prosthetic (replacement or mechanical) heart valves, and people who have suffered a heart attack. Warfarin is also used to treat or prevent venous thrombosis (swelling and blood clot in a vein) and pulmonary embolism (a blood clot in the lung). Warfarin is in a class of medications called anticoagulants ('blood thinners'). It works by decreasing the clotting ability of the blood.
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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.