Warfarin Institute of America
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NAFCILLIN INTERACTION WITH WARFARIN
Nafcillin is known to cause a need for an increased warfarin dosage because it increases the metabolism of warfarin in the liver. Qureshi et al report that one patient's half-life of warfarin was 11 hours when on warfarin and 44 hours after the warfarin was stopped.
A case reported by Libby and Gold illustrates a potent interaction between both nafcillin and rifampin with warfarin. The patient was a 43-year-old woman 5 feet 1 inch tall weighing 97 pounds. She had a history of muscular dystrophy and had a pork mitral valve in place. One week prior to admission, she had a tooth extracted with antibiotic prophylaxis. Nevertheless, she had developed an infection with Staphylocccus epidermidis. This caused vegetations on the porcine valve. She was started on IV nafcillin and gentamicin and the porcine valve was replaced with a St. Jude valve. Nafcillin was continued, gentamicin stopped and rifampin started. From day 13 to day 20, her warfarin was increased to 30 mg/day to achieve the necessary INR. Her warfarin dose eventually reached 40 mg/day. After the antibiotics were discontinued, her need for warfarin declined over the next 8 weeks to 7.5 mg/day. The difficulty in achieving a therapeutic INR resulted in a 42-day hospitalization.
Taylor et al report on a case where the dose of warfarin had to be increased to 4.5 times the level it was before the nafcillin was started. The interaction continued when the patient was switched from IV nafcillin to oral dicloxacillin.
Here is how I managed an actual patient with this combination of medications. Although the INR went fairly high on several occasions, the management was successful in that he experienced no warfarin-related problems and his original problem was resolved. This patient is a man in his fifties who has a long history of diabetes. He lost one leg in a below-knee amputation. In his other knee he had a prosthesis which became septic. This joint was removed and the infection treated with nafcillin. I was not involved in the day-to-day management of warfarin until near the end of his hospitalization. However, he was my patient for outpatient monitoring before the joint became infected, so I was familiar with his history. Prior to the infection, he had been managed on warfarin 28 mg/wk for a long time. He was not able to be very active, so the infection did not decrease his activity appreciably. Prior to his discharge, I was consulted because the house staff had been unable to get his INR above 1.2. It was at this time, that I recognized the warfarin-nafcillin interaction. I had his warfarin dose increased and ordered blood to be drawn by the home health nurses when the administered the IV nafcillin,
7/30 He continued on nafcillin and had taken warfarin 82,5 mg/wk His INR was 1.5. His warfarin dose was increased to 30 mg for each of the next two days. He was also on a therapeutic dose of enoxaparin until his INR became therapeutic.
8/1 Still on nafcillin and enoxaparin. Took warfarin 142.5 mg/wk. INR = 2.5. Take warfarin 20 mg/day for 2 days. Continue enoxaparin.
8/3 Still on nafcillin and enoxaparin. Took warfarin 160 mg/wk. INR = 2.4. Stop enoxaparin. Take warfarin 140 mg/wk.
8/7 Took warfarin 140 mg/wk. INR = 3.9. Reduce warfarin to 120 mg/wk.
8/10 Took warfarin 120 mg/wk. INR = 1,6. Increase warfarin to 130 mg/wk.
8/15 Nafcillin was stopped on 8/12. Took warfarin 130 mg/wk. INR = 1.6. Take warfarin 140 mg/wk.
8-20 Took warfarin 140 mg/wk. INR = 5.1. Hold warfarin for two days.
8-22 With the two-day hold, he has had warfarin 100 mg/wk. INR = 1.8. Reduce warfarin to 90 mg/wk.
8/27 Has had warfarin 90 mg/wk. INR = 3.8. Decrease warfarin to 80 mg/wk.
8/31 Took warfarin 80 mg/wk. INR = 4.0. Surgery is planned in a few days to insert a new knee prosthesis and the surgeon would like the warfarin held until then.
9-5 The warfarin was held as planned, but the surgeon decided that there were too many complications to do the surgery. He is to go to another surgeon specialist tomorrow. However, surgery is not expected to be done for some time yet. INR = 1.1. Resume warfarin 70 mg/wk.
9-12 Took warfarin 70 mg/wk. INR = 7.8. Hold warfarin for two days, then resume at 50 mg/wk.
9-20 Took warfarin 50 mg/wk. INR = 7.8. Hold warfarin for two days, and then return to the warfarin dose he was taking before he started nafcillin, which was 28 mg/wk.
For those who have read several pages of this website, you know that I ordinarily do not advocate checking the INR more often than once per week. I checked the INR more frequently that that in, most instances, with this patient. It made sense here because we knew that he was taking a potent combination of interacting drugs and was unlikely to reach a steady-state situation. Please notice that although the INR was checked more frequently, it was the total weekly dose on which I based any dosage changes. This also illustrates that a patient in a difficult situation is not likely to suffer harm if the INR is watched closely and not allowed to go excessively high or low for an extended period of time.
To read the case report of a patient who had both nafcillin and carbamazepine click here.
References:
Qureshi GD et al. Warfarin resistance with nafcillin therapy. Ann Intern Med 1984;100:527-529.
Libby E, Gold E. Warfarin Resistance Due to Rifampin - Nafcillin Interaction. J Thrombosis Thrombolysis 2000;9:S64 Abstract A4.
Taylor AT et al. Continuation of warfarin-nafciollin interaction during dicloxacillin therapy. J Fam Pract 1994;39:182-185
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Last updated November 14, 2004