WARNING — INTRAVENOUS AND INTRAMUSCULAR USE
Severe reactions, including fatalities, have occurred during and immediately after INTRAVENOUS injection of phytonadione, even when precautions have been taken to dilute the phytonadione and to avoid rapid infusion. Severe reactions, including fatalities, have also been reported following INTRAMUSCULAR administration. 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. Therefore the INTRAVENOUS and INTRAMUSCULAR routes should be restricted to those situations where the subcutaneous route is not feasible and the serious risk involved is considered justified.
VITAMIN K1 SUMMARY
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.
Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) 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. Vitamin K1 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 Vitamin K1 (Phytonadione)
Effects of Vitamin K on Matrix Metalloproteinase-3 and Rheumatoid Factor in Women
with Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled Trial. 
autoantibody in patients with RA... CONCLUSIONS: Vitamin K1 supplementation at 10 mg/day for 8 weeks did not alter
Differential effects of vitamin K1 on AFP and DCP levels in patients with unresectable HCC and in HCC cell lines. [2011.06]
CONCLUSIONS: Vitamin K1 was non-toxic at high doses, strongly inhibited plasma DCP levels, but weakly suppressed AFP levels. The results provide evidence that the two tumor markers are not directly linked and that DCP levels may not reflect HCC cell growth, as DCP levels were decreased in patients without AFP change, and were suppressed in vitro at 1% of the vitamin K1 concentration needed to inhibit AFP.
Nutritional supplementation of hop rho iso-alpha acids, berberine, vitamin D, and vitamin K produces a favorable bone biomarker profile supporting healthy bone metabolism in postmenopausal women with metabolic syndrome. [2011.05]
Metabolic syndrome poses additional risk for postmenopausal women who are already at risk for osteoporosis. We hypothesized that a nutritional supplement containing anti-inflammatory phytochemicals and essential bone nutrients would produce a favorable bone biomarker profile in postmenopausal women with metabolic syndrome...
Vitamin K1 supplementation to improve the stability of anticoagulation therapy with vitamin K antagonists: a dose-finding study. [2011.04]
BACKGROUND: Poor anticoagulant stability in patients using vitamin K antagonists is a risk factor for both bleeding and thrombosis. In previous studies supplementation with low dose vitamin K(1) was shown to improve the stability of anticoagulant control. We set up a study to confirm earlier reports and to determine the optimal daily dose of vitamin K(1) in preparation of a large study with clinical endpoints... CONCLUSIONS: In patients starting vitamin K antagonists, supplementation with low dose vitamin K(1) resulted in an improvement of time that anticoagulation was within the therapeutic range. Differences between doses were, however, small and the improvement is unlikely to be of clinical relevance. For future studies we recommend selecting only patients with instable anticoagulant control. (This study was registered at www.isrctn.org as ISRCTN37109430).
The cost effectiveness of a randomized controlled trial to establish the relative efficacy of vitamin K1 compared with alendronate. [2011.01]
CONCLUSIONS: It is concluded that an RCT recruiting between 2000 and 5000 women per arm to evaluate the relative efficacy of alendronate and vitamin K(1) appears to be cost effective for informing decision making in England and Wales.
Clinical Trials Related to Vitamin K1 (Phytonadione)
Trial to Assess Vitamin D Requirements in Lactating Women [Completed]
This is a randomized, placebo-controlled trial of vitamin D supplementation with 20mcg
cholecalciferol (to achieve a total intake of 25mcg/day), with or without 500mg calcium to
assess vitamin D requirements in lactating women and to ascertain whether vitamin D
supplementation at levels sufficient to achieve defined thresholds of maternal serum
25-hydroxyvitamin D will increase the vitamin D content of maternal milk. The study will
also report serum 25-hydroxyvitamin D in maternal-cord dyads over a 12-month period and
describe the relationship between them. Information on maternal iPTH levels, anthropometry,
diet and sun exposure will also be reported.
Vitamin D in Pediatric Asthma: a Randomized Controlled Open-label Pilot Trial [Recruiting]
This is a pilot randomized controlled trial of lower vs. higher dose vitamin D
supplementation in D-deficient asthmatic children, to determine necessary sample sizes for
outcome measures in a larger multisite study, and to examine possible relationships and
effect sizes between various biological markers that may be important to the pathophysiology
of childhood asthma.
Aims of the study are to:
1. Evaluate effect sizes for relationships between serum 25OH-vitD and omega-fatty acid
(FA) biomarkers, before and after supplementation with lower or higher dose vitamin D,
on immune function, and asthma severity.
2. Characterize changes in innate and adaptive immune function and inflammatory responses
in asthmatic D-deficient youth at baseline and after vitD supplements, by dietary
O6: O3FA status and vitD dose.
Vitamin D for Sickle Cell [Active, not recruiting]
Vitamin D deficiency (VDD) is very common among African American adolescents and adults in
the US, ten times higher than is seen in Caucasians. VDD is also quite common in sickle cell
disease (SCD). Both VDD and SCD can cause chronic pain, compression fractures, and muscle
weakness. The investigators believe VDD may contribute to poor musculoskeletal health and
chronic pain seen in pediatric SCD. In this study, the investigators aim to show that
children and adolescents with SCD and chronic pain have lower levels of vitamin D compared
to those without chronic pain. The investigators also aim to determine the clinical
characteristics in SCD patients related to their vitamin D status.
About 60 subjects (7 to 21 years old) will be enrolled on this study, 30 with chronic pain
and 30 without chronic pain. The investigators will assess baseline characteristics
including vitamin D levels, bone turnover rates (measured by C telopeptide blood levels
[CTx]), markers of inflammation and oxidative stress levels in blood, baseline hemoglobin
and other laboratory parameters, presence of abnormal bones on chest x-ray, pulmonary
function, opioid analgesic use, overall muscle strength, quality of life and depression.
To evaluate the impact of vitamin D replacement on these baseline characteristics, the
investigators will randomize subjects to receive either placebo or high dose vitamin D for 6
weeks after which time the investigators will evaluate overall vitamin D status, muscle and
bone health, depression, quality of life, pain status and use of opioid pain medications,
inflammation and oxidative status comparing before and after treatment with high dose
vitamin D. The investigators will give—at no cost to subjects—a daily supplement that will
provide the recommended daily allowance of calcium and vitamin D that contains 500mg Calcium
and 200IU vitamin D to subjects throughout the study period. Subjects will be in the study
for 7 months and have five to six study visits.
Vitamin D Replacement After Kidney Transplant [Not yet recruiting]
Efficacy of Vitamin D Supplementation in Bariatric Surgery Patients [Active, not recruiting]
As the use of bariatric surgery for treatment of extreme obesity adults continues to rise,
clinicians must be aware of pre-existing nutritional deficiencies in overweight and obese
patients. Nutritional deficiencies are common in patients undergoing bariatric surgery and
these deficiencies should be detected and addressed early to avoid post-operative
complications. To improve long-term outcomes following bariatric surgery, nutritional
screening and prescribing appropriate supplementation to prevent nutrient deficiencies is
needed. Vitamin D deficiency is common following bariatric surgery and has been reported to
occur in 50-80% bariatric patients. The goal of this pilot study is to help develop nutrient
supplementation interventions following two types of bariatric surgery: Roux-en Y gastric
bypass and sleeve gastrectomy.
Recently, several studies in adults have revealed an inverse relationship between body fat
and blood 25-hydroxyvitamin D3 [25(OH)D] levels, the relevant marker of low vitamin D
status. Although vitamin D is well known for its essential role in bone metabolism and
calcium homeostasis, increasing evidence is linking vitamin D to obesity. This study will
evaluate vitamin D status during post operative daily supplementation of 2,000 IU of vitamin
D3 and 1500 mg of calcium through assessment of changes in serum 25(OH)D, parathyroid
hormone (PTH), calcium and phosphorus at baseline, 4 weeks, and 12 weeks following surgery.
The dietary contribution of vitamin D and calcium will be estimated by food records analyzed
using the University of Minnesota 2010 Nutrition Data System for Research (NDSR) program.
Primary Hypothesis: Daily supplementation with 2,000 IU of vitamin D3 for 12 weeks will
significantly increase mean serum 25(OH)D levels in obese subjects following bariatric
surgery compared to baseline levels.
Secondary Hypothesis: The percent response above baseline to daily supplementation with
2,000 IU of vitamin D3 will significantly differ between Roux-en Y and sleeve gastrectomy
Page last updated: 2015-08-10