Phytonadione Tablets, USP 8460094/0121 Rx Only

Phytonadione is a vitamin which is a clear, yellow to amber, very viscous odorless or practically 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 450.70.

Phytonadione is 2-methyl-3-phytyl-1, 4-naphthoquinone. Its molecular formula is C ₃₁H ₄₆O ₂ and its structural formula is:

Structural Formula

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.

Phytonadione tablets, USP possess the same type and degree of activity as does naturally-occurring vitamin K, which is necessary for the production via the liver of active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX), and Stuart factor (factor X). The prothrombin test is sensitive to the levels of three of these four factors – II, VII, and X. Vitamin K is an essential cofactor for a microsomal enzyme that catalyzes the post-translational carboxylation of multiple, specific, peptide-bound glutamic acid residues in inactive hepatic precursors of factors II, VII, IX, and X. The resulting gamma-carboxyglutamic acid residues convert the precursors into active coagulation factors that are subsequently secreted by liver cells into the blood.

Oral phytonadione is adequately absorbed from the gastrointestinal tract only if bile salts are present. After absorption, phytonadione is initially concentrated in the liver, but the concentration declines rapidly. Very little vitamin K accumulates in tissues. Little is known about the metabolic fate of vitamin K. Almost no free unmetabolized vitamin K appears in bile or urine.

In normal animals and humans, phytonadione is virtually devoid of pharmacodynamic activity. However, in animals and humans deficient in vitamin K, the pharmacological action of vitamin K is related to its normal physiological function; that is, to promote the hepatic bio synthesis of vitamin K-dependent clotting factors.

Phytonadione tablets, USP generally exert their effect within 6 to 10 hours.

Phytonadione tablets, USP are 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 tablets, USP are indicated in:

• anticoagulant-induced prothrombin deficiency caused by coumarin or indanedione derivatives;
• hypoprothrombinemia secondary to antibacterial therapy;
• hypoprothrombinemia secondary to administration of salicylates;
• hypoprothrombinemia secondary to obstructive jaundice or biliary fistulas but only if bile salts are administered concurrently, since otherwise the oral vitamin K will not be absorbed.

Hypersensitivity to any component of this medication.

An immediate coagulant effect should not be expected after administration of phytonadione.

Phytonadione will not counteract the anticoagulant action of heparin.

When vitamin K ₁ is 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 K ₁ may restore conditions which originally permitted thromboembolic phenomena. Dosage should be kept as low as possible, and pro thrombin time should be checked regularly as clinical conditions indicate.

Repeated large doses of vitamin K are not warranted in liver disease if the response to initial use of the vitamin is unsatisfactory. Failure to respond to vitamin K may indicate a congenital coagulation defect or that the condition being treated is unresponsive to vitamin K.

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 rare 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 rarely and primarily with doses above those recommended.

The intravenous and oral LD ₅₀s in the mouse are approximately 1.17 g/kg and greater than 24.18 g/kg, respectively.

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:
Unit dose packages of 20 (2 x 10) NDC 60687-600-94

American Health Packaging unit dose blisters (see How Supplied section) contain drug product from Zydus Pharmaceuticals (USA) Inc. as follows:
(5 mg / 20 UD) NDC 60687-600-94 packaged from NDC 70710-1014

Distributed by:
American Health Packaging
Columbus, OH 43217

8460094/0121

5 mg Phytonadione Tablets Carton

NDC 60687- 600-94

Phytonadione
Tablets, USP

5 mg

20 Tablets (2 x 10)                 Rx Only

Each Tablet Contains:
Phytonadione USP..................................................................... 5 mg

USUAL ADULT DOSAGE: See package insert for full prescribing
information.

Store at 20° to 25°C (68° to 77°F); excursions permitted between
15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Keep this and all drugs out of reach of children.

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

The drug product contained in this package is from
NDC # 70710-1014, Zydus Pharmaceuticals (USA) Inc.

Distributed by:
American Health Packaging
Columbus, Ohio 43217

760094
0460094/0121

5 mg Phytonadione Tablet Blister

Phytonadione
Tablet, USP

5 mg