title: Multivitamin supplements may affect warfarin anticoagulation in susceptible patients.
abstract: OBJECTIVE
  To report an interaction of a multivitamin preparation containing small amounts of vitamin K(1) (25 microg) with warfarin in a case series and to assess the prevalence of vitamin K(1) deficiency in ambulatory anticoagulated patients.
  
  
  METHODS
  We describe 3 patients whose anticoagulation was stabilized with warfarin in whom initiation or cessation of a self-prescribed multivitamin supplement delivering 25 microg of vitamin K(1) daily was associated with an otherwise unexplained significant fall or rise in international normalized ratio (INR), respectively, with major thrombosis or hemorrhage in 2. This interaction was rated probable on the Naranjo probability scale. Suspecting vitamin K(1) deficiency as an explanation for this oversensitivity, we assessed the prevalence of vitamin K(1) deficiency in our clinic by determining plasma vitamin K(1) levels in 179 stable consecutive patients, finding very low levels (<0.1 ng/mL) in 22 of 179 (12%).
  
  
  CONCLUSIONS
  Vitamin K(1) supplements of 25 microg daily are far below the dose thought to affect anticoagulant control. We hypothesize that, in our patients, unsuspected vitamin K(1) deficiency caused an oversensitivity to small vitamin K(1) supplements. In patients with low vitamin K(1) status, even such low doses represent a significant increment in daily intake, thus lowering the sensitivity to warfarin. Our analysis suggests that low vitamin K(1) status exists in a small, but important, minority of ambulatory patients undergoing anticoagulation.
  
  
  CONCLUSIONS
  Clinicians should instruct anticoagulated patients to report the use of multivitamin supplements and inquire about it in cases of unexplained INR changes.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kurnik
authors.forename: Aharon
authors.initials: A
authors.lastname: Lubetsky
authors.forename: Ronen
authors.initials: R
authors.lastname: Loebstein
authors.forename: Shlomo
authors.initials: S
authors.lastname: Almog
authors.forename: Hillel
authors.initials: H
authors.lastname: Halkin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000493:pharmacokinetics*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D010837:Vitamin K 1 / Q000008:administration & dosage / Q000494:pharmacology*; D014859:Warfarin / Q000493:pharmacokinetics*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D010837:Vitamin K 1