Elevated International Normalized Ratio associated with concurrent use of ophthalmic erythromycin and warfarin

The case of a patient whose International Normalized Ratio (INR) increased with concurrent use of ophthalmic erythromycin and warfarin is reported.

A 77-year-old Caucasian woman began therapy with warfarin for thromboembolism prophylaxis secondary to atrial fibrillation (target INR, 2-3). Warfarin was prescribed by her cardiologist, and care was established with clinical pharmacists in an anticoagulation clinic. She was receiving a weekly maintenance dosage of 14 mg. She had a history of atrial fibrillation, hyperlipidemia, osteoarthritis, hypothyroidism, coronary artery disease, myocardial infarction, congestive heart failure, and breast cancer. In addition to warfarin, the patient had been receiving alprazolam, carvedilol, furosemide, levothyroxine sodium, lisinopril, nitroglycerin, potassium chloride, propoxyphene hydrochloride-acetaminophen, simvastatin, and trazodone. After receiving warfarin at the same weekly dosage for over four months, the patient's ophthalmologist prescribed erythromycin ophthalmic ointment for chronic bacterial conjunctivitis. Three weeks later, her INR was found to be 8.5. A total of four warfarin doses were withheld, and her weekly maintenance dosage of warfarin was subsequently decreased to 12 mg. Five weeks later, her INR was 1.5, and it was determined that the erythromycin ophthalmic ointment had been discontinued five days prior. Her weekly maintenance dosage of warfarin was increased to 16 mg. Rechallenge with erythromycin five days before her next INR measurement resulted in an INR of 4.2. A new weekly maintenance dosage of 13 mg was established, and her subsequent INRs were within normal range.

An increase in INR values was reported after initiation of ophthalmic erythromycin in a patient receiving warfarin and recurred upon rechallenge with ophthalmic erythromycin.