Drug interactions between doxycycline/omega-3 polyunsaturated fatty acids and Miradon

doxycycline ↔ anisindione

Applies to:doxycycline/omega-3 polyunsaturated fatty acids and Miradon (anisindione)

MONITOR: Tetracycline antibiotics may enhance the action of oral anticoagulants by inhibiting the production of vitamin K producing bacteria in the GI tract.

MANAGEMENT: INR should be monitored whenever a tetracycline is started or stopped, and the patient should be observed for signs of bleeding. An adjustment of the anticoagulant dose may be necessary. Patients should be advised to notify their physicians if they experience any signs of excessive anticoagulation, such as unusual or prolonged bleeding, bruising, vomiting, change in stool or urine color, headache, dizziness, or weakness.

omega-3 polyunsaturated fatty acids ↔ anisindione

Applies to:doxycycline/omega-3 polyunsaturated fatty acids and Miradon (anisindione)

MONITOR: Large doses of omega-3 polyunsaturated fatty acids (e.g., fish oil) may potentiate the hypoprothrombinemic effect of oral anticoagulants. The exact mechanism of interaction is unknown. Omega-3 polyunsaturated fatty acids may possess mild antiplatelet and hypocoagulant activities. In some studies, these substances have been shown to reduce thrombin generation and plasma levels of fibrinogen, prothrombin, and coagulation factors V, VII, and X. The interaction was suspected in a case report of a 67-year-old woman treated with warfarin for 1.5 years who exhibited an increase in INR from 2.8 the previous month to 4.3 approximately one week after doubling her fish oil dosage from 1000 to 2000 mg/day. Prior to the increase, her INR had been stable and therapeutic for 5 months while on warfarin 1.5 mg/day. The patient was advised to reduce her fish oil consumption to 1000 mg/day, while her warfarin dose was withheld for one day and then reduced to 1 mg alternating with 1.5 mg per day. Eight days later, her INR was subtherapeutic at 1.6, so the warfarin dosage was increased back to 1.5 mg/day. The patient's INR has been within therapeutic range since that time.

MANAGEMENT: In general, patients should consult a healthcare provider before taking any herbal or nutritional supplements. Patients receiving oral anticoagulant therapy in combination with omega-3 polyunsaturated fatty acids should be advised of the potential for increased hypoprothrombinemic effect. The INR should be checked frequently and anticoagulant dosage adjusted accordingly, particularly following initiation, discontinuation, or change of dosage of the fatty acids. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.