WARNING — INTRAVENOUS USE
Severe reactions, including fatalities, have occurred during and immediately after the parenteral administration of Phytonadione. Typically these severe reactions have resembled hypersensitivity or anaphylaxis, including shock and cardiac and/or respiratory arrest. Some patients have exhibited these severe reactions on receiving Phytonadione for the first time. The majority of these reported events occurred following intravenous administration, even when precautions have been taken to dilute the Phytonadione and to avoid rapid infusion. Therefore, the INTRAVENOUS route should be restricted to those situations where another route is not feasible and the increased risk involved is considered justified.
Phytonadione is a vitamin, which is a clear, yellow to amber, viscous, odorless or nearly odorless liquid. It is insoluble in water, soluble in chloroform and slightly soluble in ethanol.
Phytonadione is indicated in the following coagulation disorders which are due to faulty formation of factors II, VII, IX and X when caused by vitamin K deficiency or interference with vitamin K activity.
Phytonadione Injectable Emulsion, USP is indicated in:
- —anticoagulant-induced prothrombin deficiency caused by coumarin or indanedione derivatives;
- —prophylaxis and therapy of hemorrhagic disease of the newborn;
- —hypoprothrombinemia due to antibacterial therapy;
- —hypoprothrombinemia secondary to factors limiting absorption or synthesis of vitamin K, e.g., obstructive jaundice, biliary fistula, sprue, ulcerative colitis, celiac disease, intestinal resection, cystic fibrosis of the pancreas, and regional enteritis;
- —other drug-induced hypoprothrombinemia where it is definitely shown that the result is due to interference with vitamin K metabolism, e.g., salicylates.
Clinical Trials Related to Phytonadione
Low Dose Supplementation to Improve Anticoagulation Control With Oral Vitamin K as an Adjuvant to Warfarin Therapy [Recruiting]
The main objective of this study is to assess the effectiveness of low dose Vitamin K1 (200
micrograms per day) at improving anticoagulation control in unstable patients on warfarin.
This study will also aim to look at effectiveness in the context of genes known to influence
warfarin metabolism, variability in the consumption of Vitamin K rich foods, and patient
knowledge about warfarin anticoagulation - - factors which have been associated with
anticoagulation control and which can influence the effectiveness of this intervention in
Use of Phytonadione to Reduce International Normalized Ratio (INR) Variability in Patients on Long-term Warfarin Therapy [Recruiting]
Background: Warfarin is used as an anti-coagulant in patients at risk of developing
thrombosis. It has a narrow therapeutic index necessitating close monitoring of
International Normalized Ratio (INR). According to a meta-analysis, patients were in
therapeutic range only 63. 6% of the time. This increases the risk of bleeding or thrombosis.
Various retrospective and prospective studies have looked at supplementation with
phytonadione in these patients to reduce the variability of INR showing an improvement in
variability. Most of these studies have only been done in a small number of patients
already on warfarin therapy. This study will focus on patients newly starting warfarin
Methods: This study is a prospective, randomized, controlled trial performed at James A.
Haley Veterans' Hospital (JAHVA). Patients who meet criteria and sign informed consent
will receive either phytonadione with warfarin or warfarin alone. Based on a power
calculation for 80%, a total of 370 patients will be enrolled (185 participants in each
arm). Participants will be randomized to either intervention or control. Intervention group
participants will be prescribed their usual starting dose of warfarin along with 200 mcg
phytonadione by mouth daily. Control group participants will be prescribed their usual
starting dose of warfarin. Both groups will follow the usual standard of care. They will
come in for a follow-up INR and warfarin dose titration at least once per week until
therapeutic, and then as instructed up to every 6 weeks thereafter. Both groups will
participate in anticoagulation clinic activities that constitute the current standard of
care. Intervention will last for a total of 6 months for each participant once enrolled.
Hypothesis: Participants in the intervention group being supplemented with 200mcg of
phytonadione will spend more total time with a therapeutic INR than participants in the
Does Low Dose Oral Vitamin K Improve International Normalized Ratio (INR) Stability? [Recruiting]
Warfarin is highly effective for the prevention of both first and recurrent thrombotic
events, however even minor excursions outside the reference INR range of 2. 0 to 3. 0 are
associated with bleeding or thrombotic complications. The importance of maintaining the INR
within the desired interval has led to the concept of "time in therapeutic range (TTR)" -
the total proportion of time that the INR is between 2. 0 and 3. 0. The investigators propose
a multicentre, double blind, randomized trial which will determine if 0. 150 mg of oral
vitamin K increases time in the therapeutic range for patients receiving warfarin.
Vitamin K1 to Slow Progression of Vascular Calcification in HD Patients [Recruiting]
Patients on hemodialysis (HD) exhibit an immensely increased cardiovascular mortality
associated with extensive vascular calcification (VC). In the past years the development of
VC was discovered to be actively regulated and as being influenced by inhibitors of
calcification (e. g. matrix-Gla-protein, fetuin-A). MGP is produced by vascular smooth
muscle cells and needs post-translational modification by vitamin K dependent
gamma-carboxylation to be fully active. Based on the demonstration of increased PIVKA-II
levels, about 97% of all HD patients exhibit insufficient carboxylation activity. We
therefore aim in this randomized, controlled study to retard the progress of coronary and
aortal calcification as assessed by thoracic multislice-CT by the thrice weekly
administration of 5 mg vitamin K1 (phylloquinone) to a total of 348 HD patients over a
period of 18 months.
Oral Vitamin K for Warfarin Associated Coagulopathy [Active, not recruiting]
Excessive prolongation of the international normalized ratio (INR) occurs frequently in
patients taking warfarin; in fact, about one in six INR values is above the desired range.
Excessive prolongation of the INR is clinically important because the risk of bleeding
approximately doubles for each one point increase in the INR beyond the usual therapeutic
range. Thus, treatment strategies which rapidly and reliably lower an excessively prolonged
INR into the desired range have the potential to reduce bleeding. When taken by patients with
INR values between 4. 5 and 10, a small dose of oral vitamin K (1 mg to 2. 5mg) reduces the INR
into the desired INR range in about 75% of cases within 24 hours of its administration. If
warfarin is simply withheld, and no vitamin K is given, about 25% of patients will have an
INR in the desired range at 24 hours. However, vitamin K is rarely given to such patients. In
a recent survey carried out by our group, less than 20% of such patients would have been
given low dose oral vitamin K by a group of physicians who regularly supervise warfarin
The most common treatment for excessive prolongation of the INR is to simply withhold
warfarin and allow the INR to fall into the therapeutic range. Although this strategy is
effective its safety has never been adequately examined. In fact, recent evidence suggests
that patients with INR values of more than 6. 0 who are treated with simple warfarin
withdrawal have a risk of major bleeding of 4% in the two weeks after they develop their
When asked why they did not give oral vitamin K to a non-bleeding patient who has an
excessively prolonged INR, physicians generally give one of three reasons: (1)They are not
convinced that oral vitamin K reduces bleeding. (2) They are concerned that oral vitamin K
may cause thrombosis. (3) In contrast with simply withholding warfarin, giving oral vitamin K
requires a patient to visit the physician, and the physician must have a supply of vitamin
We hypothesize that the routine practice of not administering oral vitamin K to patients with
excessively prolonged INR values is causing patients to have major, life-threatening and
fatal bleeds. To convince physicians that oral vitamin K should be administered to all
non-bleeding patients with INR values of more than 4. 5, we propose a study which we
anticipate will demonstrate that oral vitamin K reduces bleeding, does not cause thrombosis,
and can be administered at home without direct physician supervision.
To accomplish these goals, we propose a multinational, double-blind, placebo-controlled
trial. We will randomize patients with INR values between 4. 5 and 10. 0 to receive 1. 25 mg of
oral vitamin K or placebo and follow them for bleeding and thrombosis. Patients with INR
values of more than 10. 0 will receive a single 1. 25 mg dose of oral vitamin K.
Successful completion of this study will establish a treatment standard supported by clinical
data which will, in turn, change the way that patients taking warfarin who present with an
excessively prolonged INR are treated.
Reports of Suspected Phytonadione Side Effects
Deep Vein Thrombosis (3),
Needle Issue (2),
Injection Site Haematoma (1),
Injection Site Haemorrhage (1),
Anaphylactic Reaction (1),
Hepatic Failure (1),
Renal Impairment (1)
Page last updated: 2006-05-11