Phytonadione

FDA Drug Information • Also known as: Phytonadione, Phytonadione Phytonadione, Vitamin K1

Brand Names: Phytonadione, Phytonadione Phytonadione, Vitamin K1
Dosage Form: POWDER
Product Type: BULK INGREDIENT

Description

11 DESCRIPTION Phytonadione, USP is a vitamin K replacement, which is a clear, yellow to amber, viscous, and nearly odorless liquid. It is soluble in dehydrated alcohol, in benzene, in chloroform, in ether and slightly soluble in alcohol. It has a molecular weight of 450.7. Phytonadione is 2-methyl-3-phytyl-1, 4-naphthoquinone. Its molecular formula is C 31 H 46 O 2 and its structural formula is: Each uncoated phytonadione tablet, USP for oral administration contains 5 mg of phytonadione, USP and contains following inactive ingredients: croscarmellose sodium, colloidal silicon dioxide, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate and microcrystalline cellulose. Image

What Is Phytonadione Used For?

1 INDICATIONS AND USAGE Phytonadione is indicated for the treatment of adults with 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. anticoagulant-induced hypoprothrombinemia caused by coumarin or indanedione derivatives; hypoprothrombinemia secondary 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 pancrease, 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. Phytonadione is a vitamin K replacement indicated for the treatment of adults with 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: Anticoagulant-induced prothrombin deficiency caused by coumarin or indanedione derivatives; ( 1 ) Hypoprothrombinemia secondary to antibacterial therapy; ( 1 ) 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; ( 1 ) Other drug-induced hypoprothrombinemia where it is definitively shown that the result is due to interference with vitamin K metabolism, e.g., salicylates. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Anticoagulant-Induced Prothrombin Deficiency: 2.5 mg to 10 mg or up to 25 mg ( 2.2 ) Hypoprothrombinemia Due to Other Causes: 2.5 mg to 25 mg or more ( 2.2 ) Must be given with bile salts when endogenous supply of bile to gastrointestinal track is deficient. ( 2.1 ) 2.1 Dosing Considerations Avoid the oral route when the clinical disorder would prevent proper absorption. Bile salts must be given with the tablets when the endogenous supply of bile to the gastrointestinal tract is deficient. The coagulant effects of phytonadione tablets are not immediate; improvement of international normalized ratio (INR) may take 1 to 8 hours. Interim use of whole blood or component therapy may also be necessary if bleeding is severe. Phytonadione tablets will not counteract the anticoagulant action of heparin. When phytonadione tablets are used to correct excessive anticoagulant-induced hypoprothrombinemia, anticoagulant therapy still being indicated, the patient is again faced with the clotting hazards existing prior to starting the anticoagulant therapy. Phytonadione is not a clotting agent, but overzealous therapy with vitamin K1 may restore conditions which originally permitted thromboembolic phenomena. Dosage should be kept as low as possible, and prothrombin time should be checked regularly as clinical conditions indicate. 2.2 Recommended Dosage Anticoagulant-Induced Prothrombin Deficiency in Adults The recommended dose to correct excessively prolonged prothrombin times caused by oral anticoagulant therapy is, 2.5 to 10 mg or up to 25 mg initially. In some instances 50 mg may be required. Frequency and amount of subsequent doses should be determined by prothrombin time response or clinical condition. If, in 12 to 48 hours after oral administration, the prothrombin time has not been shortened satisfactorily, repeat the dose. Repeated large doses of phytonadione tablets are not warranted in liver disease if the response to initial use of the vitamin is unsatisfactory. Failure to respond to phytonadione tablets may indicate a congenital coagulation defect or that the condition being treated is unresponsive to vitamin K. Hypoprothrombinemia Due to Other Causes in Adults If possible, discontinuation or reduction of the dosage of drugs interfering with coagulation mechanisms (such as salicylates, antibiotics) is suggested as an alternative to administering concurrent phytonadione tablets. The severity of the coagulation disorder should determine whether the immediate administration of phytonadione tablets is required in addition to discontinuation or reduction of interfering drugs. The recommended dose is 2.5 mg to 25 mg or more (sometimes up to 50 mg). Evaluate INR after 6 to 8 hours, and repeat dose if INR remains prolonged. Modify subsequent dosage (amount and frequency) based upon the INR or clinical condition.

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following adverse reactions associated with the use of parenteral phytonadione were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Severe hypersensitivity reactions, including anaphylactoid reactions and deaths, have been reported following parenteral administration. The majority of these reported events occurred following intravenous administration. Transient "flushing sensations" and "peculiar" sensations of taste have been observed with parenteral phytonadione, as well as instances of dizziness, rapid and weak pulse, profuse sweating, brief hypotension, dyspnea, and cyanosis. Hyperbilirubinemia has been observed in the newborn following administration of parenteral phytonadione. This has occurred primarily with doses above those recommended. Most common adverse reactions are transient "flushing sensations", "peculiar" sensations of taste and instances of dizziness, rapid and weak pulse, profuse sweating, brief hypotension, dyspnea, and cyanosis. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Northstar Rx LLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Drug Interactions

7 DRUG INTERACTIONS Anticoagulants Phytonadione may induce temporary resistance to prothrombin-depressing anticoagulants, especially when larger doses of phytonadione are used. Should this occur, higher doses of anticoagulant therapy may be needed when resuming anticoagulant therapy, or a change in therapy to a different class of anticoagulant may be necessary (i.e., heparin sodium). Phytonadione does not affect the anticoagulant action of heparin. Anticoagulants: May induce temporary resistance to prothrombin-depressing anticoagulants. ( 7 )

Contraindications

4 CONTRAINDICATIONS Phytonadione tablets are contraindicated in patients with a history of a hypersensitivity reaction to phytonadione or inactive ingredients [see Description ( 11 )] . Hypersensitivity to any component of this medication. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Published studies with the use of phytonadione during pregnancy have not reported a clear association with phytonadione and adverse developmental outcomes [see Data] . There are maternal and fetal risks associated with vitamin K deficiency during pregnancy [see Clinical Considerations] . Animal reproduction studies have not been conducted with phytonadione. The estimated background risk for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Pregnant women with vitamin K deficiency hypoprothrombinemia may be at increased risk for bleeding diatheses during pregnancy and hemorrhagic events at delivery. Subclinical vitamin K deficiency during pregnancy has been implicated in rare cases of fetal intracranial hemorrhage. Data Human Data Phytonadione has been measured in cord blood of infants whose mothers were treated with phytonadione during pregnancy in concentrations lower than seen in maternal plasma. Administration of vitamin K 1 to pregnant women shortly before delivery increased both maternal and cord blood concentrations. Published data do not report a clear association with phytonadione and adverse maternal or fetal outcomes when used during pregnancy. However, these studies cannot definitively establish the absence of any risk because of methodologic limitations including small sample size and lack of blinding. Animal Data In pregnant rats receiving vitamin K 1 orally, fetal plasma and liver concentrations increased following administration, supporting placental transfer.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Phytonadione Tablets USP, 5 mg are light yellow to yellow colored, round shaped, uncoated tablets engraved with "10 14" on one side and break line on other side and are supplied as follows: NDC 16714-973-01 in bottle of 100 tablets NDC 16714-973-02 in bottle of 30 tablets Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Always protect phytonadione tablets from light. Store in tightly closed original container and carton until contents have been used.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.