Interactions with Vitamin K

In a crossover design clinical study, 13 healthy volunteers were maintained on a vitamin K1-restricted diet for 35 days and were randomly assigned to take omeprazole (40 mg/day) either during the first period of study or starting on day 15 until the end of the study (Paiva et al. 1998). The bacterial overgrowth induced by omeprazole included vitamin K2 (menaquinone)-synthesizing bacteria that served as a source of vitamin K. However, these bacteria were unable to restore vitamin K status to normal.

Phenytoin

Phenytoin interferes with vitamin K metabolism (Keith et al. 1983). Clotting defects may occur in neonates born to mothers receiving anticonvulsant drugs (Solomon et al. 1977). Some researchers recommend supplementing with vitamin K in pregnant women on epileptic therapy four weeks before the expected date of delivery (Nulman et al. 1999). Other researchers have not found justification for giving vitamin K to all pregnant women on anticonvulsant therapy throughout the last trimester of pregnancy (Hey 1999).

Warfarin

Vitamin K can decrease the anticoagulant effect of warfarin by interfering with the production of vitamin K-dependent clotting factors (Bell et al. 1972; Hines Burnham et al. 2000). Oral vitamin K1 (phytonadione) is used to correct excessive anticoagulation in patients on warfarin therapy who do not have serious bleeding (Weibert et al. 1997). A prospective open label clinical study with 62 warfarin-treated patients that had elevated INR values found that vitamin K1 (1 mg po) was a safe, reliable, and economical means of reducing the INR in these patients (Crowther et al. 1998). A consistent dietary intake of vitamin K is important to maintain vitamin K status and avoid a potential warfarin-vitamin K interaction (Booth et al. 1997; Booth and Centurelli 1999). Patients should avoid drastic changes in dietary habits while on warfarin therapy. Individuals taking warfarin may require more intensive monitoring of vitamin K status and INR values.

References

Bell RG, Sadowski JA, Matschiner JT. Mechanism of action of warfarin. Warfarin and metabolism of vitamin K1. Biochem. 1972;11:1959-1961.

Booth SL, Centurelli MA. Vitamin K: a practical guide to the dietary management of patients on warfarin. Nutr Rev. 1999;57(9 Pt 1):288-293.

Booth SL, Charnley JM, Sadowski JA, Saltzman E, Bovill EG, Cushman M. Dietary vitamin K1 and stability of oral anticoagulation: proposal of a diet with constant vitamin K1 content. Thromb Haemost. 1997;77(3):504-509.

Crowther MA, Donovan D, Harrison L, McGinnis J, Ginsberg J. Low-dose oral vitamin K reliably reverses over-anticoagulation due to warfarin. Thromb Haemost. 1998;79:1116-1118.

Hey E. Effect of maternal anticonvulsant treatment on neonatal blood coagulation. Arch Dis Child Fetal Neonatal Ed. 1999;81(3):F208-210.

Hines Burnham, et al, eds. Drug Facts and Comparisons. St. Louis, MO:Facts and Comparisons; 2000:179.

Keith DA, Gundberg CM, Japour A, et al. Vitamin-K dependent proteins and anticonvulsant medication. Clin Pharmacol Ther. 1983;34(4):529-532.

Nulman I, Laslo D, Koren G. Treatment of epilepsy in pregnancy. Drugs. 1999;57(4):535-544. Published erratum appears in Drugs. 1999;57(6):870.

Paiva SAR, Sepe TE, Booth SL, et al. Interaction between vitamin K nutriture and bacterial overgrowth in hypochlorhydria induced by omeprazole. Am J Clin Nutr. 1998;68:699-704.

Solomon GE, Hilgartner MW, Kutt H. Antivonvulsant-induced depression of clotting factors in children. Neurol Neurocir Psiquiatr. 1977;18(2-3 Suppl):277-284.

Weibert RT, Le DT, Kayser SR, et al. Correction of excessive anticoagulation with low-dose oral vitamin K1. Ann Intern Med. 1997;126(12):959-962.

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