Drug interactions between Miradon and Natalcare Plus

anisindione ↔ multivitamin, prenatal

Applies to:Miradon (anisindione) and Natalcare Plus (multivitamin, prenatal)

MONITOR: Multivitamin preparations containing vitamin K may antagonize the hypoprothrombinemic effect of oral anticoagulants in some patients. Vitamin K1 in its active, reduced form serves as a cofactor in the generation of functional clotting factors, during which it becomes oxidized. It is reactivated in a process that is inhibited by oral anticoagulants, thus intake of additional vitamin K through supplements or diet can reverse the action of oral anticoagulants. Although the amount of vitamin K in over-the-counter multivitamin preparations is generally well below the dose thought to affect anticoagulation, there have been isolated case reports of patients stabilized on warfarin whose INR decreased following initiation of a multivitamin supplement and returned to therapeutic levels upon cessation of the multivitamin. Increases in warfarin dosage were required in some cases when the multivitamin was continued. One patient whose warfarin dosage was increased developed a subcapsular hematoma in her right kidney two weeks after she discontinued the multivitamin without informing her physician. Her INR was 13.2 and she was treated with vitamin K and fresh frozen plasma. It is possible that patients with low vitamin K status may be particularly susceptible to the interaction. Investigators have shown that vitamin K deficiency can cause an oversensitivity to even small increases in vitamin K intake. In one study where warfarin-stabilized patients were given a multivitamin tablet containing 25 mcg of vitamin K1 daily for 4 weeks, subtherapeutic INRs occurred in 9 of 9 patients with low vitamin K1 levels (<1.5 mcg/L) and only 1 of 7 patients with normal vitamin K1 levels (>4.5 mcg/L). INR decreased by a median of 0.51 and warfarin dosage had to be increased by 5.3% in patients with low vitamin K1 levels, whereas INR and warfarin dosage did not change significantly in patients with normal vitamin K1 levels. The prevalence of vitamin K deficiency may be small, but significant in the anticoagulated population. In a survey of 179 consecutive ambulatory patients on stable warfarin therapy attending an anticoagulation clinic, 22 (12.3%) were found to have vitamin K1 deficiency (<0.1 ng/mL).

MANAGEMENT: The potential for multivitamin supplements containing even low levels of vitamin K to affect anticoagulation should be recognized. In particular, elderly and/or malnourished patients may require more frequent monitoring of INR following the initiation or discontinuation of a multivitamin supplement, and the anticoagulant dosage adjusted as necessary.