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.
2-methyl-3-phytyl-1, 4-naphthoquinone. Its empirical formula is C31H46O2 and its structural formula is:
MEPHYTON1 (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
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 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 biosynthesis of vitamin K-dependent clotting factors.
MEPHYTON tablets generally exert their effect within 6
to 10 hours.
INDICATIONS AND USAGE
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.
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.
will not counteract the anticoagulant action of heparin.
When vitamin K1is 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.
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.)
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.
Prothrombin time should be checked regularly as clinical
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 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.
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.
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.
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.
Severe hypersensitivity reactions, including anaphylactoid
reactions and deaths have been reported following parenteral administration.
The majority of these reported events occurred following intravenous
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,
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 LD50s in the
mouse are approximately 1.17 g/kg and greater than 24.18 g/kg,
DOSAGE AND ADMINISTRATION
MEPHYTON Summary of Dosage Guidelines (See circular text for details)
Anticoagulant-Induced ProthrombinDeficiency (caused by coumarin or
2.5 mg-10 mg or up
to 25 mg (rarely 50 mg)
Hypoprothrombinemia due toother causes (Antibiotics;
Salicylates or other drugs; Factors limiting absorption or synthesis)
2.5 mg-25 mg or more (rarely up
to 50 mg)
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
No. 7776 — 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 0006-0043-68 bottles of 100.
Store in tightly closed
original container at 25°C (77ºF); 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.)
Merck & Co.,
Whitehouse Station, NJ 08889, USA
Issued April 2004
Printed in USA
HUMAN PRESCRIPTION DRUG
Item Code (Source)
Route of Administration
Name (Active Moiety)
5 MILLIGRAM In 1 TABLET
colloidal silicon dioxide
contains a BOTTLE
This package is contained within the CARTON (0006-0043-68)