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.
AquaMEPHYTON 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.
AquaMEPHYTON injection 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.
Published Studies Related to Aquamephyton (Phytonadione)
Comparison of oral vs intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study. [2003.11.10]
BACKGROUND: Treatment of patients with excessive anticoagulation is routinely done by intravenous phytonadione (vitamin K1). Oral administration of phytonadione has been shown to be an effective alternative to the intravenous route, but these methods have never been compared directly. Our objective was to compare efficacy and safety of intravenous vs oral phytonadione treatment in patients with excessive anticoagulation without bleeding... CONCLUSION: Oral administration of phytonadione had similar efficacy and safety as intravenously administered phytonadione and may be suitable for treatment of patients with excessive anticoagulation.
Randomized, placebo-controlled trial of oral phytonadione for excessive anticoagulation. [2000.10]
STUDY OBJECTIVE: To compare the efficacy of managing excessive anticoagulation in the absence of bleeding by either omitting warfarin therapy alone or administering oral phytonadione in addition to omitting warfarin therapy... CONCLUSION: The addition of oral phytonadione 2.5 mg reduced the time to achieve an INR of 4.0 by approximately 1 day compared with omitting warfarin therapy alone. Adverse events did not differ between the two groups. Both strategies were effective in managing asymptomatic patients with INRs of 6.0-10.0. Oral phytonadione may be most appropriate for patients at high risk for bleeding in whom the benefit of prompt INR reduction would outweigh the thromboembolic risk associated with INR overcorrection.
Time course of reversal of anticoagulant effect of warfarin by intravenous and subcutaneous phytonadione. [1999.12.13]
BACKGROUND: Excessive anticoagulation increases the risk of hemorrhagic complications associated with oral anticoagulant therapy. Oral or parenteral phytonadione is used to reverse excessive anticoagulation. Intravenous (IV) phytonadione, while effective, is associated with a small risk of serious anaphylactic reactions. Subcutaneous (SC) administration is safer, but there is little information on its relative efficacy in small doses... CONCLUSIONS: For patients who are excessively anticoagulated with warfarin, small doses of SC phytonadione may not correct the INR as rapidly or as effectively as when administered IV. Higher doses must be considered for more rapid and complete reversal of anticoagulation by the SC route.
Reversal of excessive effect of regular anticoagulation: low oral dose of phytonadione (vitamin K1) compared with warfarin discontinuation. [1993.10]
To determine the best way to reverse the excessive effect of regular anticoagulation in patients with INR > 5 and no bleeding complications, 23 patients with INR > 5 were randomly subdivided into two groups: group A (n = 12) discontinued warfarin for one day and group B (n = 11) received 2 mg of vitamin K1 orally in addition to the usual warfarin dose...
Treatment of excessive anticoagulation with phytonadione (vitamin K): a meta-analysis. [2006.02.27]
BACKGROUND: Patients taking oral anticoagulants with an international normalized ratio (INR) greater than 4.0 are at increased risk for bleeding. We performed a meta-analysis to determine the effectiveness of phytonadione (vitamin K) in treating excessive anticoagulation... CONCLUSIONS: Limited evidence suggests that oral and intravenous vitamin K are equivalent and more effective for excessive anticoagulation than simply withholding warfarin sodium. Subcutaneous vitamin K, however, is inferior to oral and intravenous vitamin K for this indication and is similar to placebo. Whether treatment with vitamin K decreases hemorrhagic events cannot be determined from the published literature.
Clinical Trials Related to Aquamephyton (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 as Additive Treatment in Osteoporosis [Not yet recruiting]
Vitamin K is thought to be important for bone health because it activates several proteins
involved in bone formation. Poor dietary intake of vitamin K (mainly found in dark green
leafy vegetables) is associated with bone loss and fractures. Giving supplements of the main
dietary form of vitamin K (called K1) or another common form which our bodies make from
K1(called MK4), to improve bone health have given mixed results. This confusion is thought
to have arisen because these studies involved people who already had enough vitamin K or did
not have osteoporosis. We want to test the hypothesis that treatment with bisphosphonates
combined with vitamin K, in vitamin K deplete elderly women with osteoporosis, may offer
additional benefit on skeletal metabolism and reduction of fracture risk. We want to test
this by measuring vitamin K status in post-menopausal women with osteoporosis who are on the
recommended treatment with a bisphosphonate and calcium/vitamin D supplements. Those with
low vitamin K will then be recruited to study the effect of supplementation with either K1