Warfarin with Rifampin Interaction Details

Brand Names Associated with Warfarin

Brand Names Associated with Rifampin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 07, 2023

Interaction Effect

Decreased anticoagulant effectiveness of warfarin

Interaction Summary

Rifampin is a strong CYP450 hepatic enzyme inducer and concomitant administration with warfarin may cause increased metabolism and decreased effectiveness of warfarin as reported in several case reports. Therefore, use caution if these agents are coadministered. When adding or withdrawing rifampin therapy in patients on warfarin, monitor prothrombin time (PT) and the international normalized ratio (INR) frequently  as adjustments of the warfarin dose may be necessary. When used with rifampin, high doses of warfarin (20 mg/day or greater) may be needed to maintain adequate anticoagulation  and a 50% reduction of the warfarin dose should be considered within 1 to 2 weeks after rifampin is discontinued  with further reduction if necessary thereafter . Monitor patients for signs and symptoms of subtherapeutic anticoagulation (eg, redness or swelling of legs or extremities, sudden onset shortness of breath).

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Use caution if warfarin is coadministered with a known CYP450 enzyme inducer, such as rifampin, as this may lead to increased metabolism and decreased effectiveness of warfarin. When adding or withdrawing rifampin therapy in a patient on warfarin, monitor prothrombin time (PT) and the international normalized ratio (INR) frequentlyas adjustments of the warfarin dose may be necessary. When used with rifampin, high doses of warfarin (20 mg/day or greater) may be needed to maintain adequate anticoagulation  and a 50% reduction of the warfarin dose should be considered within 1 to 2 weeks after rifampin is discontinued with further reduction if necessary thereafter . Monitor patients for signs and symptoms of subtherapeutic anticoagulation (eg, redness or swelling of legs or extremities, sudden onset shortness of breath).

Mechanism Of Interaction

Hepatic enzyme induction causing increased warfarin metabolism

Literature Reports

A) A 79-year-old man with a history of deep vein thrombosis, pulmonary embolism, and peripheral arterial disease did not maintain adequate anticoagulation on warfarin when receiving concurrent rifampin for osteomyelitis. The patient, who was admitted to the hospital for skin grafting as a result of bilateral venous stasis ulcers on the ankles, received rifampin 300 mg orally twice daily and intravenous (IV) ertapenem and vancomycin in addition to surgery for the treatment of osteomyelitis. He had previously been maintained on warfarin 5 mg orally once daily (international normalized ratio (INR) range, 1.9 to 2.9) for 8 months but warfarin was discontinued and he was placed on enoxaparin 120 mg subcutaneously every 12 hours on admission. Warfarin was restarted 11 days after surgery and the patient had intermittent subtherapeutic INRs (below 2) despite high doses of warfarin (range, 5 to 30 mg/day); therefore, warfarin was discontinued for the remainder of rifampin therapy and enoxaparin was restarted. Warfarin 5 mg once daily was resumed one month later when rifampin was discontinued (following a 3-day warfarin load of 25 mg/day for 2 days and 30 mg/day for one day); however, a subtherapeutic INR (1.3) 2 days later required the warfarin dose to be increased. The warfarin dosage was changed many times over the next several weeks (range, 5 to 10 mg/day) and about 2 months after rifampin was stopped, the patient was stabilized (INR range, 2.2 to 3) on warfarin 7.5 mg on Tuesdays, Thursdays, and Saturdays with warfarin 5 mg given on the other days of the week .

B) A 58-year-old man with pulmonary tuberculosis and Mycobacterium avium-intracellulare receiving oral rifampin, developed a left ventricle thrombus and did not consistently achieve target anticoagulation goal with warfarin therapy until rifampin was discontinued. The patient had been receiving rifampin 600 mg/day, in addition to ethambutol and pyrazinamide, for 4 months prior to starting intravenous IV heparin therapy (for 5 days) and warfarin therapy. While the patient was on both rifampin and warfarin (dose increased from 5 to 25 mg/day) , international normalized ratio (INR) values ranged from 0.8 to 1.9 (target INR, 2.5; target INR range, 2 to 3) with the exception of one INR which was 2.3 when the patient was also receiving cefotaxime and metronidazole for suspected diverticulitis. When rifampin was discontinued after completing 9 months of therapy, the patient's warfarin dose was slowly reduced from 20 mg/day over 4 to 5 weeks in an attempt to achieve a therapeutic INR (range, 1.6 to 4.1). The patient was finally stabilized on warfarin 7.5 mg daily (INR range, 1.9 to 2.6) through the end of the case report .

C) A 36-year-old man who developed a pulmonary embolism in the hospital did not achieve adequate anticoagulation with warfarin therapy while receiving oral rifampin for a right antecubital fossa abscess. The patient was admitted to the hospital with signs and symptoms of infection and received intravenous (IV) vancomycin and gentamicin for Staphylococcus aureus bacteremia and an arm abscess. On the third hospital day, the patient was switched to IV cefazolin and oral rifampin (600 mg/day); additionally, he was diagnosed with a pulmonary embolism and started on IV heparin. Warfarin 10 mg orally daily was initiated on hospital day 5 and despite continued increases in the warfarin dose (range, 5 to 30 mg/day), the patient's prothrombin time (PT) was below the target therapeutic range for the majority of his hospitalization. Warfarin levels were performed on hospital day 25 and the baseline warfarin level was undetectable after warfarin 20 mg dose. Upon discharge, rifampin was discontinued and warfarin was decreased from 20 mg daily to 5 mg daily for two days and then increased to 10 mg daily with therapeutic PT achieved; however, the patient was soon lost to follow-up. Based on the warfarin levels obtained, the calculated warfarin clearance for this patients was approximately 23 milliliters/minute (mL/min) with a warfarin half-life of 0.47 hours (normal warfarin half-life range, 30 to 45 hours) .

D) The mechanism of action for the decrease in hypoprothrombinemia when rifampin and warfarin are administered concomitantly was clarified. Rifampin increases the clearance of (R)-warfarin 3-fold and (S)-warfarin 2-fold. Based on formation clearance values estimated for 6, 7, and 8-hydroxywarfarin, rifampin appears to increase the clearance of the parent drug by induction of the CYP450 isoenzyme responsible for aromatic hydroxylation .

Warfarin Overview

• 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.

Rifampin Overview

• Rifampin is used with other medications to treat tuberculosis (TB; a serious infection that affects the lungs and sometimes other parts of the body). Rifampin is also used to treat some people who have Neisseria meningitidis (a type of bacteria that can cause a serious infection called meningitis) infections in their noses or throats. These people have not developed symptoms of the disease, and this treatment is used to prevent them from infecting other people. Rifampin should not be used to treat people who have developed symptoms of meningitis. Rifampin is in a class of medications called antimycobacterials. It works by killing the bacteria that cause infection.

• Antibiotics such as rifampin will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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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.