A 65-year-old male patient with a history of atrial fibrillation is currently taking warfarin to manage his condition. He develops cellulitis on his right lower leg, and the physician prescribes dicloxacillin. Which of the following is true regarding the potential drug interaction of dicloxacillin with warfarin?
A) The INR most likely would increase significantly while on both agents
B) The INR most likely would decrease significantly while on both agents
C) The affect on INR would be dependent on the total dose of dicloxacillin administered
D) No significant drug interaction should be expected
Rationale:
All antibiotics have the potential to interact with warfarin and therefore need to be taken seriously. Some are very significant (e.g. trimethoprim/sulfamethoxazole, fluconazole, etc.) while others typically minimally interact (e.g. amoxicillin) Sometimes the right answer is to avoid the interaction altogether while many times the antibiotic can be administered but more intensive monitoring of INR is required. Most antibiotics increase INR and therefore increase risk of bleeding while on warfarin. Some however like rifampin can decrease INR due to enzyme induction. Which brings us to our question of the week with dicloxacillin, a rarely but still used antistaphylococcal penicillin.
Brand/Generics: Warfarin (Coumadin); Dicloxacillin (Diclox)
Answer A is incorrect as dicloxacillin is an enzyme inducer not inhibitor and therefore most likely would cause an increase in warfarin metabolism and thus decreased INR.
Answer B is correct. Dicloxacillin is a significant enzyme inducer of several CYP enzymes, including 2C9 which is important for S-warfarin metabolism. This could in turn decrease the INR and increase the risk for a thrombotic even. The really problematic issue with this interaction is that the INR can remain decreased for several weeks after the dicloxacillin is discontinued! Therefore in this case, a better option for management would likely be cephalexin which would be expected to have minimal interaction.
Answer C is incorrect. Due to the enzymatic nature of the interaction, the interaction is not a function of dose of dicloxacillin. CYP drug interactions are typically not dose related while adverse effects of drugs are often dose-related.
Answer D is incorrect due to above discussion in other answers.
Reference:
Potential Interaction between warfarin and dicloxacillin
Naplex Competency Statements
Area 3.8 Drug Interactions
See everyone next week. Hope you are having a great summer.
Dr. B
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