Warfarin and Nafcillin Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Warfarin
Nafcillin Injection
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Reduced warfarin exposure, reduced INR/prothrombin time and anticoagulant effectiveness
Interaction Deep Dive
Coadministration of nafcillin (CYP3A4 inducer) with warfarin (CYP3A4 substrate) may reduce warfarin exposure2. It may also result in increased warfarin metabolism, reduced INR or prothrombin time (PT), and reduced anticoagulant response. A 2- to 4-fold increase in the warfarin dose may be necessary to maintain therapeutic anticoagulation. When possible, substitute nafcillin with an antibiotic that has a low-risk profile for an interaction with warfarin 4. 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 1, especially during initiation and discontinuation of the antibiotic 3. Consider the CYP3A4 inhibition potential when changing dose of concomitant medications 2.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of warfarin
Literature reports
3 reports — tap to read
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 4.
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 5.
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 6.
Common questions
Can I take Warfarin and Nafcillin Injection together?
Reduced warfarin exposure, reduced INR/prothrombin time and anticoagulant effectiveness Always confirm with your pharmacist or prescriber before making any change.
How serious is the Warfarin and Nafcillin Injection interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Warfarin or Nafcillin Injection need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (6)
- Product Information: nafcillin IV injection, nafcillin IV injection. Baxter Healthcare Corporation (per FDA), Deerfield, IL, 2011.
- Product Information: WARFARIN SODIUM oral tablets, warfarin sodium oral tablets. Teva Pharmaceuticals (per Dailymed), Parsippany, NJ, 2023. DailyMed
- Product Information: COUMADIN(R) oral tablets, intravenous injection powder lyophilized for solution, warfarin sodium oral tablets, intravenous injection powder lyophilized for solution. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2011. DailyMed
- Kim KY, Frey RJ, Epplen K, et al: Interaction between warfarin and nafcillin: case report and review of the literature. Pharmacotherapy 2007; 27(10):1467-1470. PubMed
- Taylor AT, Pritchard DC, Goldstein AO, et al: Continuation of warfarin-nafcillin interaction during dicloxacillin therapy. J Fam Pract 1994; 39:182-185.
- Qureshi GD, Reinders TP, Somori GJ, et al: Warfarin resistance with nafcillin therapy. Ann Intern Med 1984; 100:527-529. PubMed
Keep reading about Warfarin
Keep reading about Nafcillin Injection
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