Warfarin with Nafcillin Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Brand Names Associated with Nafcillin
- Ethoxynaphthamido Penicillin Sodium
- Nafcillin Injection
- Sodium Nafcillin
- Unipen® Injection
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 nafcillin and warfarin may result in increased warfarin metabolism, decreased INR or prothrombin time (PT), and decreased anticoagulant response. Decreased warfarin effects have been reported with high-dose nafcillin therapy (ie, 2 g every 4 hours), which may persist for up to 30 days after nafcillin discontinuation. Additional PT/INR monitoring is recommended , especially during initiation and discontinuation of the antibiotic . A 2- to 4-fold increase in the warfarin dose may be necessary to maintain therapeutic anticoagulation . When possible, substitute nafcillin with an antibiotic with a low-risk profile for an interaction with warfarin.
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Concomitant use of nafcillin and warfarin may result in decreased INR/prothrombin time (PT) and decreased warfarin efficacy and this effect may persist up to 30 days after nafcillin discontinuation. If concomitant use is required, more frequent monitoring of INR/PT is recommended during therapy and potentially up to 30 days after nafcillin discontinuation , and especially during initiation and discontinuation of the antibiotic . A 2- to 4-fold increase in warfarin dosage may be necessary to maintain anticoagulation goals . If possible, substitute nafcillin with an antibiotic with a low-risk profile for 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 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 .
C) Warfarin resistance occurred during concomitant nafcillin administration in a 29-year-old man . Nafcillin 2 g every four hours intravenously was added to warfarin therapy (12.5 mg daily) resulting in decreased prothrombin time, despite an increase in warfarin dosage to 25 mg daily. Pharmacokinetic analysis indicated that the decreased anticoagulant effect of warfarin was secondary to increased metabolism induced by nafcillin. The elimination half-life of warfarin was 11 hours during nafcillin treatment, and 44 hours without nafcillin .
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.
Nafcillin Overview
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Nafcillin injection is used to treat infections caused by certain types of bacteria. Nafcillin injection is in a class of medications called penicillins. It works by killing bacteria.
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Antibiotics such as nafcillin injection will not work for colds, flu, or other viral infections. Taking 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:
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.