Warfarin with Oxacillin Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 07, 2023
Interaction Effect
Decreased INR/prothrombin time and anticoagulant effectiveness
Interaction Summary
The concomitant use of oxacillin with warfarin may result in decreased INR/prothrombin time (PT) and decreased warfarin effectiveness. Although use of oxacillin and warfarin has not been specifically studied, concurrent use of other penicillinase-resistant penicillins (eg, dicloxacillin, nafcillin) has resulted in decreased INR/PT and decreased warfarin efficacy, requiring significant increase in warfarin dosage. If concomitant use is necessary, a 2- to 4-fold increase in warfarin dosage may be necessary to maintain anticoagulation goals and more frequent monitoring of INR is recommended , especially during initiation and discontinuation of the antibiotic . When possible, substitute oxacillin with an antibiotic with a low-risk profile for an interaction with warfarin.
Severity
Major
Onset
Delayed
Evidence
Theoretical
How To Manage Interaction
Use caution with concomitant use of oxacillin and warfarin. Although use of oxacillin and warfarin has not specifically been studied, concurrent use of other penicillinase-resistant penicillins (eg, dicloxacillin, nafcillin) has resulted in decreased INR/prothrombin time (PT) and decreased warfarin efficacy, requiring significant increase in warfarin dosage. If concomitant use of oxacillin and warfarin is required, a 2- to 4-fold increase in warfarin dosage may be necessary to maintain anticoagulation goals and more frequent monitoring of INR/PT is recommended , especially during initiation and discontinuation of the antibiotic . If possible, substitute oxacillin with an antibiotic with a low-risk profile for an interaction with warfarin.
Mechanism Of Interaction
Increased warfarin metabolism
Literature Reports
A) A 39-year-old man treated with warfarin for a history of deep vein thrombosis experienced subtherapeutic INR values following addition of nafcillin. Prior to the addition of nafcillin, his INR values maintained within target range (goal INR, 2 to 3) with warfarin 32 mg/week for approximately 1 month. Septic arthritis of the left knee was diagnosed and initially treated with cefazolin, without notable impact on his INR. However, when the antibiotic regimen was changed from cefazolin to nafcillin 2 g every 4 hours, his INR declined significantly to 1.2 after 2 weeks of nafcillin therapy. In order to reestablish a therapeutic INR, his warfarin dosage was increased to a maximum of 88 mg/week. Following completion of nafcillin, the patient's warfarin requirement declined over several weeks and stabilized at 42 to 48 mg/week. His INR value eventually reached 2.3 .
B) A 73-year-old man, previously stable on chronic warfarin therapy for atrial fibrillation, experienced repeated subtherapeutic INR values during concomitant dicloxacillin therapy for recurrent cellulitis. For over 3 years, the patient achieved therapeutic INR values (goal INR, 2 to 3) at weekly warfarin dosages of 35 to 40 mg/week, with 35 of 47 INR values within the target range. Of 12 INR values outside the target range, 7 were supra-therapeutic (INR, 3.03 to 4.09) and 5 were subtherapeutic. All subtherapeutic INR values occurred during or within 2 weeks of finishing a course of dicloxacillin. On 2 occasions he received dicloxacillin 500 mg every 6 hours for 10 days and a third course for 30 days. When interviewed about each low INR value, the patient reported no changes in dietary vitamin K intake or warfarin adherence issues, and he denied other medication changes. In response to the low INR values noted during or within 2 weeks of concurrent dicloxacillin, the patient's warfarin dosage was increased incrementally up to 50 to 60 mg/wk. Despite this 71.4% increase in weekly warfarin dosage, the patient’s INR remained subtherapeutic for several weeks after dicloxacillin was stopped. Application of the Naranjo probability criteria rated the interaction between dicloxacillin and warfarin as definite .
C) A 41-year-old man who received warfarin 22 mg per week for recurrent DVT was started on dicloxacillin 500 mg 4 times daily for 10 days for cellulitis of the left foot. His prothrombin time (PT) decreased from 20.4 seconds at baseline to 16.9 seconds on day 5 of dicloxacillin therapy. This represented a 17% decrease. The PT returned to baseline some time between 9 and 22 days after dicloxacillin was discontinued. A retrospective review of 7 patients who were on concurrent warfarin and dicloxacillin therapy was conducted. All patients were required to have received stable doses of warfarin for at least 2 weeks prior to the start of dicloxacillin therapy and could have no changes in medications known to inhibit or induce the metabolism of warfarin within the past 2 weeks. Five of the seven patients experienced a fall in their prothrombin time (PT) large enough to require an increase in their warfarin dose. The decrease in PT appeared to occur within 4 to 5 days after the initiation of dicloxacillin .
D) A 31-year-old man with a history of rheumatic fever and aortic valve replacements was using warfarin 10 mg per day and had a prothrombin time (PT) of 21.6 seconds. He was hospitalized with acute bacterial endocarditis and started on nafcillin 2 g intravenously every 4 hours. Nine days later his PT was 13.3 seconds and his dose of warfarin was increased to 45 mg per day. On discharge, he began dicloxacillin 4 g per day and warfarin 35 mg per day, which was tapered to 15 mg. After 4 years he did not return to his previous warfarin dose of 10 mg per day. The mechanism of action was postulated to be induction of hepatic microsomal enzymes .
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.
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.