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Over‐the‐counter vitamin K1‐Containing multivitamin supplements disrupt oral anticoagulation in susceptible patients‐a prospective trial
Author(s) -
Kurnik D.,
Rabinovitz H.,
Loebstein R.,
Austerweil N.,
Almog S.,
Halkin H.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.100
Subject(s) - medicine , warfarin , multivitamin , ambulatory , prospective cohort study , odds ratio , gastroenterology , vitamin , atrial fibrillation
Background Most over‐the counter multivitamin supplements (MV) contain far less vitamin K 1 (VK) than amounts considered to affect oral anticoagulation. We have described 3 cases in whom a MV containing 25 μg VK lowered INR with severe clinical complications, suggesting that patients with low VK plasma levels are sensitive to even small VK supplements. Aim To determine whether a MV (Centrum Plus ® , 25 μg VK) affects warfarin anticoagulation, depending on baseline plasma VK. Methods Distribution of total plasma VK levels (vitamin K 1 + K 1 ‐epoxide) was determined in 100 stable ambulatory patients at therapeutic INRs. 9 patients with “low” (<1.5 ng/ml,<10 th percentile) and 7 with “normal” (>4.5 ng/ml, median) levels received 1 daily tablet of Centrum Plus ® for 4 weeks, with twice weekly INR control. Outcomes were: (1) need for warfarin dose change in response to subtherapeutic INR (<2.0 or <2.5 by target INR) (2) mean daily warfarin dose and mean INR on MV compared with baseline. Results In patients with low vs. normal VK, respectively, dose increases were required in 9/9 and 1/7 (p<0.001); the odds ratio for a dose increase>10%, at any visit during the study period, was 5.2 (95% CI, 3.1–8.2). Mean INR decreased (by 0.45, p<0.01), and mean warfarin dose increased (by 8.3 %, p<0.01) in the low VK‐group, only. Conclusion Centrum Plus ® supplements result in subtherapeutics INRs in patients with low VK levels. Anticoagulated patients should refrain from the unsupervised use of MV. Clinical Pharmacology & Therapeutics (2004) 75 , P27–P27; doi: 10.1016/j.clpt.2003.11.100