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
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
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, placebo controlled study to retard the progress of
coronary and aortal calcification as assessed by thoracic multislice-CT by the daily
administration of 1080 µg vitamin K1 (MK-7) to a total of 344 HD patients over a period of
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
Comparing Different Routes and Doses of Phytonadione (Vitamin K) for Reversing Warfarin Treated Patients With Hip Fracture Before Surgery [Not yet recruiting]
It is well known that femoral neck fractures carry a significant increase in patients'
mortality and that surgical intervention is the preferred treatment.
Any delay in operating on such patients would inevitably increase their risk of developing
complications. One of the reasons for such unintentional delay would be the hypercoagulative
status of patients taking warfarin. The CHEST 2008 guidelines suggest reversing warfarin
with Vitamin K for patients who need urgent operation. The aim of this study is to compare
different roots and doses of Vitamin K.
Vitamin K to Attenuate Coronary Artery Calcification in Hemodialysis Patients [Not yet recruiting]
The purpose of this study is to see if vitamin K supplementation three times per week
reduces the progression of coronary artery calcification over 6 months in dialysis patients
compared to placebo?
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