Warfarin with Fluvastatin Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Brand Names Associated with Fluvastatin
- Fluvastatin
- Lescol®
- Lescol® XL
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 07, 2023
Interaction Effect
An increased risk of bleeding
Interaction Summary
No change in warfarin protein binding or in prothrombin time was observed during in vitro and preliminary in vivo studies. However, seven case reports suggest a suspected interaction between warfarin and fluvastatin .
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
In patients receiving warfarin, closely monitor the prothrombin time ratio or international normalized ratio (INR) with the addition and withdrawal of fluvastatin therapy, and reassess coagulation parameters periodically during concurrent therapy. Adjustments of the warfarin dose may be necessary in order to maintain the desired level of anticoagulation.
Mechanism Of Interaction
Increased warfarin serum concentrations due to inhibition of CYP2C9-mediated S-warfarin metabolism
Literature Reports
A) In an in vivo study, fluvastatin sodium (40 mg daily for eight days) and warfarin (30 mg once) were administered to young healthy male subjects. No elevations in racemic warfarin concentrations were noted. In addition, there was no effect on prothrombin complex activity compared to placebo and warfarin. In vitro studies at therapeutic concentrations also demonstrated that fluvastatin had no effect on warfarin protein binding .
B) Supratherapeutic elevation of the international normalized ratio (INR) occurred in a 67-year-old man receiving concomitant therapy with warfarin and fluvastatin. Maintained on a stable regimen of warfarin 4 milligrams (mg) daily for over 5 months (target INR between 2 and 3), the patient had received concomitant therapy with atorvastatin 20 mg daily while on warfarin, without incident. Nine weeks after converting to fluvastatin 80 mg/day (extended release formulation), his INR measured at 6.6. The patient denied episodes of bruising or bleeding, and had not changed his warfarin regimen. He was converted back to atorvastatin, warfarin was discontinued for 4 days and then dose-adjusted 1 week later, and within 4 weeks, his INR returned to within target range .
C) There were three cases of patients reported receiving stable warfarin dosages with therapeutic international normalized ratio (INR) who exhibited an increase in the INR when fluvastatin was added to their medication regimen. Reduction of the warfarin dose was required to achieve an appropriate level of anticoagulation. Until more is understood about the concomitant use of warfarin and fluvastatin, it is advisable to monitor patients for a change in the hypoprothrombinemic response to warfarin when fluvastatin is initiated, discontinued, or the dosage is changed .
D) When a 68-year-old woman on warfarin (42.5 mg per week) was given fluvastatin 20 mg daily, the international normalized ratio (INR) increased to 4.17 after two weeks of fluvastatin therapy. Reduction of the warfarin dose was required to achieve a therapeutic INR (range 2.5-3.5). Fluvastatin was discontinued after two months secondary to insomnia. An 83-year-old female was stabilized on warfarin 22 mg per week with resulting INRs of 1.84-2.73. Fluvastatin 20 mg daily was added to therapy, and the INR increased to 3.47 in one week. The warfarin dose was decreased to 14 mg per week, and the INR decreased to 1.67. However, the patient discontinued fluvastatin therapy due to dizziness, and the warfarin dose was increased to its pre-fluvastatin levels, with the subsequent INRs returning to the therapeutic range. The third patient, a 51-year-old male, received warfarin 60 mg per week, resulting in INRs of 1.95-3.4. After one week of fluvastatin therapy at 20 mg daily, the patient reported rectal bleeding, and the INR was 4.2. When warfarin was decreased to 52.5 mg weekly, the INR dropped to 3.2 within six days. Four months later, the patient continued on fluvastatin therapy, and the INRs remained in the therapeutic range .
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.
Fluvastatin Overview
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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.
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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 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:
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.