Vitamin K: Oral vs IV

Availability:

• Vitamin K1 1mg/ml
• Vitamin K1 10mg/ml

General

• Vitamin K is a specific antidote for warfarin.
• A sustained response is achieved with intravenous Vitamin K.
• Oral or intravenous administration of vitamin K can be expected to reverse warfarin 4 – 6 hours after administration.
• Only 0.5mg vitamin K is required to reduce the INR from about 5.0 to a target level of 2.0-3.0.
• Vitamin K tablets usually contain >5mg which will completely reverse anticoagulation.
• When partial correction is required, consider intravenous vitamin K phytomenadione (Konakion MM) or give the intravenous preparation orally.
• Allergic reactions following intravenous vitamin K are rare with new preparations.
• If the INR is still too high at 24 hours, the dose of vitamin K can be repeated.

Absorption

• Under normal physiological conditions, 40- 70% of an oral dose of K1 is absorbed from the jejunum and ileum of the upper intestine and as for other fat-soluble vitamins and highly lipid-soluble nutrients, the intraluminal phase of absorption involves the solubilisation of K1 into mixed micelles
• A study found that only 20% of patients given the oral MM formulation developed an incremental serum K1 rise _ 10 ng/ml at 24 h, compared with all but one (94%) of those given i.v. K1.
• Intestinal absorption of MM K1 in these patients was unreliable, so that there is no rationale to change our current practice of recommending i.v. K1 to patients with severe liver disease and an associated coagulopathy.
• Based on the findings of a markedly prolonged serum K1 half-life in these patients, a single dose of 10 mg K1 given i.v. appears to be sufficient to maintain supraphysiological vitamin K blood levels for at least a week.

Similarities

• Some studies have shown Oral administration of phytonadione to have similar efficacy and safety as intravenously administered phytonadione and may be suitable for treatment of patients with excessive anticoagulation

Recommendation

• Intravenous vitamin K works faster than oral vitamin K, but is associated with anaphylactoid reaction in 3/10,000 patients

References:

1. Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease failure
2. PL Detail-Document, How to Manage High INRs in Warfarin Patients. Pharmacist’s Letter/Prescriber’s Letter. May 2012
3. Guidelines for Reversal of Oral Anticoagulants including Warfarin and Phenindione. West Suffolk Hospital NHS Trust
4. Lubestsky A et al. "Comparison of oral vs intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study". Arch Intern Med. 2003. 163(20):2469-2473