title: Over-the-counter vitamin K1-containing multivitamin supplements disrupt warfarin anticoagulation in vitamin K1-depleted patients. A prospective, controlled trial.
abstract: Most multivitamin supplements contain far less vitamin K(1) than thought to affect warfarin anticoagulation. Having described 3 patients with multivitamin-warfarin interactions, we hypothesized that vitamin K(1)-depleted patients are sensitive to even small increments. Therefore, we compared the effect of a vitamin K(1)-containing multivitamin on warfarin anticoagulation between patients with low versus normal vitamin K(1) status. We screened 102 warfarin-treated patients and recruited nine with "low" (< 1.5 mcg/L, 10(th) percentile) (group 1) and 7 with "normal" (>4.5 mcg/L, median) (group 2) total vitamin K(1) plasma levels (vitamin K(1) + vitamin K(1) 2,3-epoxide). Patients received one multivitamin tablet containing 25 mcg of vitamin K(1) daily, for 4 weeks (period 1). A predefined algorithm was used to adjust warfarin doses if the INR was outside the therapeutic range. Patients requiring warfarin increments were then switched to 4 weeks of a vitamin K(1)-free multivitamin supplement (period 2). During period 1, subtherapeutic INRs occurred in 9/9 and 1/7 patients in group 1 and 2, respectively (p <0.001). In group 1, INR decreased by a median of 0.51 (p <0.01), and warfarin dose had to be raised by 5.3% (p <0.01), whereas INR and warfarin dose did not change significantly in group 2. During period 2 (7 patients), there were trends towards decreased total vitamin K(1) and rising INRs associated with significantly lower warfarin doses. We conclude that vitamin K(1)-containing multivitamins reduce INR in patients with low vitamin K(1) status. Our study suggests that vitamin K-depleted patients are sensitive to even small changes in vitamin K(1) intake.
authors.affiliation: The Division of Clinical Pharmacology and Toxicology and Anticoagulation Clinic, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kurnik
authors.forename: Ronen
authors.initials: R
authors.lastname: Loebstein
authors.forename: Hadas
authors.initials: H
authors.lastname: Rabinovitz
authors.forename: Naomi
authors.initials: N
authors.lastname: Austerweil
authors.forename: Hillel
authors.initials: H
authors.lastname: Halkin
authors.forename: Shlomo
authors.initials: S
authors.lastname: Almog
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D019587:Dietary Supplements; D004336:Drug Antagonism; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D004366:Nonprescription Drugs; D010837:Vitamin K 1 / Q000097:blood / Q000494:pharmacology*; D014813:Vitamin K Deficiency; D014859:Warfarin / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*
chemical_list: D000925:Anticoagulants; D004366:Nonprescription Drugs; D014859:Warfarin; D010837:Vitamin K 1