Antibiotic and Anticoagulation: Watching Warfarin Levels Emily Seamans, PharmD Candidate Monday February 26, 2018
Warfarin (Coumadin) is the most commonly prescribed anticoagulant to prevent thromboembolisms in patients with atrial fibrillation, venous thromboembolism, and prosthetic heart valves. Providers must closely monitor the degree of anticoagulation in patients on warfarin using the international normalized ratio (INR). Many patients have an INR target range between 2 and 3 or between 2.5 and 3.5, depending on the indication for anticoagulant therapy, ensuring appropriate anticoagulation and avoiding thrombosis and bleeds.1 For patients to achieve an INR in their therapeutic range, they must maintain consistent vitamin K intake and adhere to their medication.2 Providers must titrate warfarin doses appropriately and regularly review patients’ medications for possible interactions. A patient’s INR can increase or decrease with newly prescribed or discontinued medications. Retail health care providers are in an optimal position to monitor for drug interactions between warfarin and antibiotics because 80% to 90% of all antibiotics are prescribed in an outpatient setting.3 WHEN TO WORRY Prescribers must consider how adding and removing medications will affect a patient’s INR. Medications that interact with warfarin often have a unidirectional effect on INR. If a patient’s INR is already stabilized on warfarin and an INR-increasing antibiotic but the antibiotic is discontinued, the patient’s INR could drop below the therapeutic range. Similarly, if a patient is controlled on warfarin but a provider begins an INR-increasing antibiotic, the patient’s INR could rise above the therapeutic range.1
MANY INTERACTIONS, SEVERAL CAUSES Warfarin is metabolized by the cytochrome (CYP) P450 enzyme system, specifically, CYPs 1A2, 3A4, and 2C9.2 Medications that inhibit these CYP enzymes reduce warfarin's metabolism, increasing its effect, and increase INR. Medications that induce these CYP enzymes increase warfarin's metabolism, decreasing its therapeutic effect, and decrease INR. Medications can also directly