Mephyton ® (phytonadione) Vitamin K 1 Tablets Rx only

Phytonadione is a vitamin which is a clear, yellow to amber, viscous, and nearly odorless liquid. It is insoluble in water, soluble in chloroform and slightly soluble in ethanol. It has a molecular weight of 450.70.

Phytonadione is 2-methyl-3-phytyl-1, 4-naphthoquinone. Its empirical formula is C₃₁H₄₆O₂ and its structural formula is:

Mephyton (phytonadione) tablets containing 5 mg of phytonadione are yellow, compressed tablets, scored on one side. Inactive ingredients are acacia, calcium phosphate, colloidal silicon dioxide, lactose, magnesium stearate, starch, and talc.

Mephyton tablets 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 posttranslational 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 biosynthesis of vitamin K-dependent clotting factors.

Mephyton tablets generally exert their effect within 6 to 10 hours.

Mephyton 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.

Mephyton tablets 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 K₁ 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 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.

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.

To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

The intravenous and oral LD₅₀s in the mouse are approximately 1.17 g/kg and greater than 24.18 g/kg, respectively.

Product: 68151-0158

NDC: 68151-0158-0 1 TABLET in a PACKAGE

Manufactured for:
Valeant Pharmaceuticals North America LLC
Bridgewater, NJ 08807 USA

Manufactured by:
Valeant Pharmaceuticals International, Inc.
Steinbach, MB R5G 1Z7, Canada

Mephyton is a trademark of Valeant Pharmaceuticals International, Inc. or its affiliates.
©Valeant Pharmaceuticals North America LLC

Rev. 11/16

9571300-20001736