Oral vitamin K in treatment of excessive anticoagulation

Oral and intravenous (IV) vitamin K are equivalent at 24 hours and more effective than subcutaneous vitamin K or withholding warfarin sodium³

In a meta-analysis of data from 21 studies, the following proportion of patients had reached target INR levels by 24 hours after vitamin K administration¹* *A meta-analysis was performed on data from 21 studies (10 randomized, and 11 nonrandomized, prospective studies) in which vitamin K was used to treat patients without major hemorrhage and with an INR >4.0 due to oral anticoagulant use. Target INR levels were 1.8 to 4.0 by 24 hours after administration of vitamin K.

Oral vitamin K lowered INR more rapidly than subcutaneous vitamin K in warfarin-associated coagulopathy²

In a randomized, controlled trial, patients with an INR between 4.5 and 10.0 associated with warfarin therapy, on the day after vitamin K administration^2†:

• 58% of patients receiving oral vitamin K (n=26) achieved therapeutic INR^†
• 24% of patients receiving subcutaneous vitamin K achieved therapeutic INR (P=0.015)

^†A randomized, controlled trial in which patients with an INR between 4.5 and 10.0 associated with warfarin therapy had their warfarin withheld and received vitamin K 1 mg orally or subcutaneously. Therapeutic INR: 1.8 to 3.2.

At 24 hours after administration, orally and IV-administered vitamin K₁ had similar efficacy and safety in patients with baseline INR of 6.0 to 10.0 and in patients with baseline INR>10.0^3‡

^‡A prospective, randomized study in which 44 patients with an INR of 6.0 to 10.0 (47 episodes) received either 0.5 mg of IV or 2.5 mg of oral vitamin K₁ and 17 patients (19 episodes) with INR >10.0 received 1 mg of IV or 5 mg of oral vitamin K₁.

Oral vitamin K is effective for non-urgent correction of elevated INR, returning patients to safe INR levels without over-reversal^4§

^§Results from data collected over a 2-year period from 223 patients who were asymptomatic or had minor symptoms. Patients were treated with an oral regimen devised by the investigators using the intravenous preparation of vitamin K. Patients with INR between 8.9 and 11.9 (n=166) received 2.5 mg; those with an INR of 12.0 - 20.0 (n=36) or >20 (n=21) received 5 mg.

References:

1. DeZee KJ, Shimeall WT, Douglas KM, et al. Treatment of excessive anticoagulation with phytonadione (vitamin K): a metaanalysis. Arch Intern Med. 2006;166:392-397.
2. Crowther MA, Douketis JD, Schnurr T, et al. Oral vitamin K lowers the international normalized ratio more rapidly than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy: a randomized, controlled trial. Ann Intern Med. 2002;127:251-254.
3. Lubetsky A, Yonath H, Olchovsky D, et al. A comparison of oral vs intravenous phytonadione (vitamin K₁) in patients with excessive anticoagulation: a prospective, randomized controlled study. Arch Intern Med. 2003;168:2469-2473.
4. Baker P, Gleghorn A, Tripp T, et al. Reversal of asymptomatic over-anticoagulation by orally administered vitamin K. Br J Haematol. 2006;133:331-336.