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by 40 hours.16 Vitamin K is light sensitive and needs to be protected from light.

Compounding of Oral Solution From Injectable
Vitamin K
Injectable vitamin K can also be compounded into a solution
for oral use.16,18 Sewell and Palmer studied stability of vitamin K 1 mg/mL oral solution prepared with Cremophor
EL.18 Cremophor EL is a mixture of polyethoxylated castor
oils that serves as a solubilizer and stabilizer for compounds.
The recipe consists of combining 100 mg of injectable vitamin K with 2 g of Cremophor EL. The mixture is further
diluted with water for injection to a final volume of 100 mL.
The solution needs to be sparged with nitrogen for 3 minutes
and then passed through a 0.2-µm filter. The final solution is
transferred to 1-mL amber syringes for oral administration.
The authors concluded that the solution has a shelf life of 6
months when stored at 4°C to 6°C as no loss of vitamin K
and no microbial contamination was noted for 25 weeks.
Cremophor EL has been previously associated with various undesirable reactions such as anaphylactoid reactions,
changes in blood viscosity, and erythrocyte aggregation.18
Therefore, one study used simple syrup or water for injection
instead of Cremophor EL.6,19 The authors concluded that the
suspension prepared with syrup can be stored for 111 days
and the suspension with water for injection for 104 days at
room temperature as long as both suspensions are packaged
in amber bottles. This Canadian study was published in
French, and the original reference is not cataloged in
PubMed. Thus, the results of this study need to be carefully
interpreted as no access to the original article is available,
and methods of the study cannot be properly evaluated.
However, the University of Michigan Health System confirmed the listed beyond-use dating for compounding with
simple syrup or sterile water with Sandoz Canada.7

USP 795 Guidelines
The United States Pharmacopeia (USP) recommendations for
nonsterile compounding, USP 795, include statements regarding beyond-use dating.20 The USP 795 guideline states, Oral
formulations containing water should have beyond-use dating of 14 days at refrigerated temperatures. If oral solutions
do not contain water, the beyond-use dating can be extended
to 6 months or to the expiration date of individual ingredients, whichever is earlier. Per USP 795, the recommended
beyond-use dates only apply to products without available
stability information.

Conclusion
Previous studies have shown that intravenous vitamin K is
well tolerated when administered orally and works quickly

Hospital Pharmacy 52(9)
to correct supratherapeutic INRs. Injectable vitamin K can
be given orally using the undiluted injectable formulation or
compounded into an oral solution. The stability of undiluted
injectable formulation is limited to 30 days while compounded oral solutions have longer stability depending on
the recipe used. Because recipes have stability information,
the more restrictive USP 795 guidelines would not apply to
these formulations. Information on efficacy and stability of
injectable vitamin K formulations prepared for oral administration provides an additional option for health care systems
when vitamin K tablets are unavailable or cost-prohibitive
to use.
Author's Note
Some elements of this article appear on the University of Illinois
Drug Information Group website: https://pharmacy.uic.edu/departments/pharmacy-practice/centers-and-sections/drug-informationgroup/2014/2015-faqs/nov-2015-faqs. These elements have been
written by the same author-Janna Afanasjeva.

Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.

Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.

References
1. Mephyton [package insert]. Bridgewater, NJ: Valeant; 2016.
2. Phytonadione injectable [package insert]. El Monte, CA:
International Medication Systems; 2013.
3. Kalus JS. Pharmacologic interventions for reversing the effects
of oral anticoagulants. Am J Health Syst Pharm. 2013;70(10)
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4. Orange book: approved drug products with therapeutic
equivalence evaluations. US Food and Drug Administration.
http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm.
Accessed May 10, 2016.
5. Tran HA, Chunilal SD, Harper PL, Tran H, Wood EM, Gallus
AS. An update of consensus guidelines for warfarin reversal.
Med J Aust. 2013;198(4):198-199.
6. Vanier MC, Ngo TT. Reversal of overanticoagulation with
vitamin K1: a plea for oral administration. Can J Hosp Pharm.
2006;59:125-135.
7. Stumpf JL, Ciarkowski SL, Leja N, Jaynes EK. Phytonadione
oral liquid. Am J Health Syst Pharm. 2016;73(12):858-861.
8. Keeling D, Baglin T, Tait C, et al. Guidelines on oral anticoagulation with warfarin-fourth edition. Br J Haematol.
2011;154(3):311-324.
9. Crowther MA, Donovan D, Harrison L, McGinnis J, Ginsberg
J. Low-dose oral vitamin K reliably reverses over-anticoagulation due to warfarin. Thromb Haemost. 1998;79(6):1116-1118.
10. Crowther MA, Julian J, McCarty D, et al. Treatment of warfarin-associated coagulopathy with oral vitamin K: a randomised
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https://pharmacy.uic.edu/departments/pharmacy-practice/centers-and-sections/drug-information-group/2014/2015-faqs/nov-2015-faqs https://pharmacy.uic.edu/departments/pharmacy-practice/centers-and-sections/drug-information-group/2014/2015-faqs/nov-2015-faqs https://pharmacy.uic.edu/departments/pharmacy-practice/centers-and-sections/drug-information-group/2014/2015-faqs/nov-2015-faqs http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm

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