Decreased Hypoprothrombinemic Response to Warfarin Secondary to the Warfarin-Nafcillin Interaction

Shovick, Virginia A.; Rihn, Thomas L.

doi:10.1177/106002809102500605

Cited by 13 publications

(8 citation statements)

References 8 publications

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“…Previous reports suggested that penicillinase-resistant penicillins can induce cytochrome P450 isoenzymes involved in warfarin metabolism and lead to warfarin-resistance [4,5,6,7,8,9,10,11,12,13]. Cloxacillin-induced changes in warfarin metabolism cannot explain the increased anticoagulation activity in this case.…”

Section: Discussionmentioning

confidence: 69%

“…The literature does not provide strong evidence of the clinically significant interaction between warfarin and penicillinase-resistant penicillins. Several reports document warfarin-resistance in patients treated with dicloxacillin, nafcillin, and flucloxacillin [4,5,6,7,8,9,10,11]. This drug-induced warfarin-resistance often develops within 7 days of starting antibiotic therapy.…”

Section: Discussionmentioning

confidence: 99%

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Enhanced anticoagulant effect of warfarin in a patient treated with cloxacillin

Marušić¹,

Gojo-Tomic²,

Bacic-Vrca³

et al. 2012

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Objective: To present the case of warfarin-cloxacillin interaction that resulted in an increased international normalized ratio (INR). Case summary: A 70-year-old man had been treated with warfarin for atrial fibrillation. He was hospitalized because of superficial thrombophlebitis of the left median cubital vein, which developed after venipuncture. An antibiotic therapy with cloxacillin was initiated immediately after the admission. Two days later, INR value increased from baseline 1.9 to 4.6. Anticoagulation therapy was discontinued and INR value was measured daily. His INR remained high for the entire duration of antibiotic therapy. Three days after the cloxacillin therapy was discontinued, the INR decreased to the baseline value. Discussion: In the presented case, the temporal relationship between the administration of cloxacillin and increased INR suggests that the cloxacillin was responsible for the enhanced warfarin activity. According to the Drug Interaction Probability Scale, a causal relationship between the warfarin-cloxacillin interaction and increased INR value was rated "probable". Conclusion: Interactions between warfarin and cloxacillin can result in serious adverse reactions. INR value should be closely monitored when patients are prescribed this combination of drugs.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Enhanced anticoagulant effect of warfarin in a patient treated with cloxacillin

Marušić¹,

Gojo-Tomic²,

Bacic-Vrca³

et al. 2012

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“…Three other case reports documenting a warfarin-nafcillin interaction have described a 2-5-fold increase in warfarin requirements with nafcillin coadministration. [8][9][10] In a review of warfarin induction interactions, induction by nafcillin was usually evident within 1 week, and warfarin requirements returned to baseline doses 1-4 weeks after nafcillin discontinuation. 12 The authors of a review of warfarin drug and food interactions determined that this drug interaction was highly probable.…”

Section: Discussionmentioning

confidence: 99%

“…Authors of case reports also have suggested that nafcillin leads to warfarin resistance due to nonselective enzyme induction. [5][6][7][8][9][10] Although the authors of one report suggested that dicloxacillin also may induce CYP enzymes, 10 this effect has not been reported with oxacillin.…”

Section: Discussionmentioning

confidence: 99%

Interaction Between Warfarin and Nafcillin: Case Report and Review of the Literature

et al. 2007

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A 39-year-old man with a history of deep vein thrombosis and septic arthritis of the left knee was treated with warfarin and cefazolin. Therapeutic prothrombin times and international normalized ratios (INRs) were maintained with warfarin 32 mg/week for approximately 1 month. When the patient's antibiotic regimen was changed from cefazolin to nafcillin 2 g every 4 hours, his INR declined significantly. His warfarin dosage had to be increased to a maximum of 88 mg/week to achieve a therapeutic INR. After completion of antibiotic therapy with nafcillin, the patient's warfarin requirements slowly declined over several weeks. A maintenance dosage of warfarin 42-48 mg/week was necessary after nafcillin discontinuation. Hepatic cytochrome P450 isoenzyme induction by nafcillin is likely the mechanism of a warfarin-nafcillin interaction. The usual onset of effect is within 1 week after starting nafcillin, and the offset of the effect is usually evident within 4 weeks after nafcillin discontinuation. In patients taking warfarin who are prescribed nafcillin, a 2-4-fold increase in the warfarin dose may be necessary, and clinicians should closely monitor INRs.

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“…Within the 9 published case reports, a total of 11 patient cases were described including: 4 warfarin-naïve patients at the time nafcillin was initiated (1 of which was a pediatric patient), 4 stable warfarin patients prior to initiation of nafcillin, 2 stable warfarin patients prior to initiation of dicloxacillin, and 1 stable warfarin patient at the time of nafcillin initiation that was changed to dicloxacillin. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] In the warfarin-naïve patients, higher initial warfarin doses (5-12 mg/day) were needed initially during nafcillin treatment. The weekly warfarin doses were typically two-to fourfold higher than the doses after discontinuation of nafcillin.…”

Section: Introductionmentioning

confidence: 99%

Significant drug–drug interaction between warfarin and nafcillin

King

Babcock

Godios

et al. 2018

Therapeutic Advances in Drug Safety

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Nafcillin, a beta-lactam semisynthetic penicillin, is highly resistant to penicillinase and is similar to other penicillins except that it is primarily metabolized in the liver. It is believed that nafcillin causes CYP3A4 enzyme induction which decreases warfarin's half-life. The onset of CYP3A4 induction by nafcillin occurs within the first 7 days, but maximal effects may take up to 2 weeks. Once nafcillin is discontinued, the effects persist for several weeks. A 79-year-old male with a history of atrial fibrillation and a 53-year-old male with a history of recurrent venous thromboembolism required significantly higher weekly warfarin doses during courses of nafcillin therapy. Both patients required a 2.5-3.5-fold increase from their baseline weekly warfarin dose to achieve therapeutic international normalized ratios (INRs) while on nafcillin. Traditional protocol-driven warfarin management can result in suboptimal anticoagulation in patients on warfarin and nafcillin.

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Decreased Hypoprothrombinemic Response to Warfarin Secondary to the Warfarin-Nafcillin Interaction

Cited by 13 publications

References 8 publications

Enhanced anticoagulant effect of warfarin in a patient treated with cloxacillin

Enhanced anticoagulant effect of warfarin in a patient treated with cloxacillin

Interaction Between Warfarin and Nafcillin: Case Report and Review of the Literature

Significant drug–drug interaction between warfarin and nafcillin

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