Phytonadione (Phytonadione) - Summary

PHYTONADIONE SUMMARY

PHYTONADIONE INJECTABLE
EMULSION, USP

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.

NEWS HIGHLIGHTS

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 clinical practice.

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.

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 therapy.

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 prolonged INR.

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 K.

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.

Vitamin K Supplementation in Post-Menopausal Osteopenia [Active, not recruiting]
The purpose of this study is to determine whether supplementation with 5 mg vitamin K daily over a 2-year period will prevent bone loss in post-menopausal women with osteopenia.

Does Low Dose Oral Vitamin K Improve International Normalized Ratio (INR) Stability? [Not yet 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.

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