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.

Last updated on RxList: 12/2/2008

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.

MEPHYTON Summary of Dosage Guidelines (See circular text for details)

Adults	Initial Dosage
Anticoagulant-Induced Prothrombin Deficiency (caused by coumarin or indanedione derivatives)	2.5 mg-10 mg or up to 25 mg (rarely 50 mg)
Hypoprothrombinemia due to other causes (Antibiotics; Salicylates or other drugs; Factors limiting absorption or	2.5 mg-25 mg or more (rarely up to 50 mg)

Anticoagulant-Induced Prothrombin Deficiency in Adults

To correct excessively prolonged prothrombin times caused by oral anticoagulant therapy – 2.5 to 10 mg or up to 25 mg initially is recommended. In rare instances 50 mg may be required. Frequency and amount of subsequent doses should be determined by prothrombin time response or clinical condition. (See WARNINGS.) If, in 12 to 48 hours after oral administration, the prothrombin time has not been shortened satisfactorily, the dose should be repeated.

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 MEPHYTON. The severity of the coagulation disorder should determine whether the immediate administration of MEPHYTON is required in addition to discontinuation or reduction of interfering drugs.

A dosage of 2.5 to 25 mg or more (rarely up to 50 mg) is recommended, the amount and route of administration depending upon the severity of the condition and response obtained.

The oral route should be avoided 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.

Tablets MEPHYTON, 5 mg vitamin K1, are yellow, round, scored, compressed tablets, coded MSD 43 on one side and MEPHYTON on the other. They are supplied as follows:

NDC 25010-405-15 bottles of 100.

Storage

Store in tightly closed original container at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Always protect MEPHYTON from light. Store in tightly closed original container and carton until contents have been used. (See PRECAUTIONS, General.)

Distributed by: Aton Pharma, Lawrenceville, NJ 08648, USA. Manufactured by: Merck and Co., Inc. West Point, PA 19486, USA. Issued May 2007. FDA Rev date: 2/9/2004

Last updated on RxList: 12/2/2008

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.

Temporary resistance to prothrombin-depressing anticoagulants may result, especially when larger doses of phytonadione are used. If relatively large doses have been employed, it may be necessary when reinstituting anticoagulant therapy to use somewhat larger doses of the prothrombin-depressing anticoagulant, or to use one which acts on a different principle, such as heparin sodium.

Laboratory Tests

Prothrombin time should be checked regularly as clinical conditions indicate.

Last updated on RxList: 12/2/2008

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.

General

Vitamin K1 is fairly rapidly degraded by light; therefore, always protect MEPHYTON from light. Store MEPHYTON in closed original carton until contents have been used. (See also HOW SUPPLIED, Storage.)

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies of carcinogenicity or impairment of fertility have not been performed with MEPHYTON. MEPHYTON at concentrations up to 2000 mcg/plate with or without metabolic activation, was negative in the Ames microbial mutagen test.

Pregnancy

Pregnancy Category C: Animal reproduction studies have not been conducted with MEPHYTON. It is also not known whether MEPHYTON can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. MEPHYTON should be given to a pregnant woman only if clearly needed.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established with MEPHYTON. Hemolysis, jaundice, and hyperbilirubinemia in newborns, particularly in premature infants, have been reported with vitamin K.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when MEPHYTON is administered to a nursing woman.

Geriatric Use

Clinical studies of MEPHYTON did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Last updated on RxList: 12/2/2008

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

Hypersensitivity to any component of this medication.

Last updated on RxList: 12/2/2008

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, peptidebound glutamic acid residues in inactive hepatic precursors of factors II, VII, IX, and X. The resulting gammacarboxyglutamic 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.

Last updated on RxList: 12/2/2008

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 12/2/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

VITAMIN K - ORAL

COMMON BRAND NAME(S): Mephyton

USES: Vitamin K is used to treat and prevent low levels of certain substances (blood clotting factors) that your body naturally produces. These substances help your blood to thicken and stop bleeding normally (e.g., after an accidental cut or injury). Low levels of blood clotting factors increase the risk for unusual bleeding. Low levels may be caused by certain medications (e.g., warfarin) or medical conditions (e.g., obstructive jaundice). Vitamin K helps to treat and prevent unusual bleeding by increasing the body's production of blood clotting factors.

HOW TO USE: Take this medication by mouth exactly as directed by your doctor. Dosage is based on your medical condition and response to treatment.

If you are using a certain "blood thinner" drug (warfarin), vitamin K can decrease the effects of warfarin for up to 2 weeks. Therefore, be sure to take your vitamin K and warfarin exactly as directed by your doctor or pharmacist.

If you develop easy bruising or bleeding, seek immediate medical attention. You may need another dose of vitamin K.

SIDE EFFECTS: Vitamin K usually has very few side effects. If you have any unusual effects from taking this medicine, tell your doctor or pharmacist promptly.

If your doctor has prescribed this medication, remember that he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, tell your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking vitamin K, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: blood disorders, gallbladder disease (e.g., obstructive jaundice, biliary fistula), liver disease.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this medication passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: "blood thinners" (e.g., warfarin), aspirin, nonsteroidal anti-inflammatory drugs-NSAIDs (e.g., ibuprofen, naproxen).

Avoid taking this medication at the same time as orlistat (a weight-management drug). Wait at least 2 hours between taking this medication and orlistat because taking them together may decrease the effect of vitamin K.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., prothrombin time, INR) should be performed to monitor your progress or check for side effects. Consult your doctor for more details.

Vitamin K is commonly found in leafy green vegetables such as spinach, collards, and broccoli. Follow any dietary guidelines recommended by your health care professional.

MISSED DOSE: If you are taking this product on a prescribed schedule and miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.