Menadione sod bisulphite
The properties are similar to vit k, so look down at vit k record for details.
Vitamin K
Indications: Coagulopathy; Hypoprothrombinemia, secondary to antibacterial therapy; Hypoprothrombinemia, secondary to anticoagulant therapy; Hypoprothrombinemia, secondary to biliary fistula; Hypoprothrombinemia, secondary to obstructive jaundice; Hypoprothrombinemia, secondary to salicylates; Hypoprothrombinemia, secondary to vitamin K deficiency
WARNING:
Injection: Severe reactions, including fatalities, have occurred during and immediately after intravenous injection of vitamin K, even when precautions have been taken to dilute the vitamin K and to avoid rapid infusion. Typically these severe reactions have resembled hypersensitivity or anaphylaxis, including shock and cardiac and/or respiratory arrest. Some patients have exhibited these severe reactions on receiving vitamin K for the first time. Therefore the intravenous route should be restricted to those situations where other routes are not feasible and the serious risk involved is considered justified.
DESCRIPTION:
Phytonadione is a vitamin, which is a clear, yellow to amber, viscous, odorless or 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.
Injection: Vitamin K injection is a yellow, sterile, aqueous colloidal solution of vitamin K1, with a pH of 5.0 to 7.0, available for injection by the intravenous, intramuscular, and subcutaneous routes. Each Milliliter Contains: Phytonadione 2 mg or 10 mg. Inactive Ingredients: Polyoxyethylated fatty acid derivative 70 mg, dextrose 37.5 mg and water for injection, q.s. 1 ml. Added as Preservative: Benzyl alcohol 0.9%.
Tablets: Mephyton 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.
CLINICAL PHARMACOLOGY:
Injection and Tablets
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.
Injection
Vitamin K aqueous colloidal solution for parenteral injection possesses 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.
Phytonadione is readily absorbed following intramuscular administration. 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.
The action of the aqueous colloidal solution, when administered intravenously, is generally detectable within an hour or two and hemorrhage is usually controlled within 3 to 6 hours. A normal prothrombin level may often be obtained in 12 to 14 hours.
In the prophylaxis and treatment of hemorrhagic disease of the newborn, phytonadione has demonstrated a greater margin of safety than that of the water-soluble vitamin K analogues.
Tablets
Vitamin K 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 micorsomal 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 intially 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 apears in bile or urine.
INDICATIONS AND USAGE:
Vitamin K 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.
Injection
Vitamin K injection is indicated in:
* Anticoagulant-induced prothrombin deficiency caused by coumarin or indanedione derivatives.
* Prophylaxis and therapy of hemorrhagic disease of the newborn.
* Hypoprothrombinemia due 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 pancreas, 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.
Tablets
Vitamin K 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.
CONTRAINDICATIONS:
Hypersensitivity to any component of this medication.
WARNINGS:
Injection and Tablets
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 that the condition being treated is inherently unresponsive to vitamin K.
Injection
Benzyl alcohol as a preservative in bacteriostatic sodium chloride injection has been associated with toxicity in newborns. Data are unavailable on the toxicity of other preservatives in this age group. There is no evidence to suggest that the small amount of benzyl alcohol contained in vitamin K, when used as recommended, is associated with toxicity.
An immediate coagulant effect should not be expected after administration of phytonadione. It takes a minimum of 1 to 2 hours for measurable improvement in the prothrombin time. Whole blood or component therapy may also be necessary if bleeding is severe.
Tablets
An immediate coagulant effect should not be expected after administration of phytonadione.
PRECAUTIONS:
General
Tablets: 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.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Injection: Studies of carcinogenicity, mutagenesis or impairment of fertility have not been conducted with vitamin K.
Tablets: Studies of carcinogenicity or impairment of fertility have not been performed with vitamin K. Vitamin K 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 vitamin K. It is also not known whether vitamin K can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Vitamin K should be given to a pregnant woman only if clearly needed.
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 vitamin K is administered to a nursing woman.
Pediatric Use
Injection: Hemolysis, jaundice, and hyperbilirubinemia in newborns, particularly in premature infants, may be related to the dose of vitamin K. Therefore, the recommended dose should not be exceeded (see ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION).
Tablets: Safety and effectiveness in pediatric patients have not been established with vitamin K. Hemolysis, jaundice, and hyperbilirubinemia in newborns, particularly in premature infants, have been reported with vitamin K.
DRUG INTERACTIONS:
Injection
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.
ADVERSE REACTIONS:
Injection
Deaths have occurred after intravenous administration. (See BOXED WARNING.)
Transient "flushing sensations" and "peculiar" sensations of taste have been observed, as well as rare instances of dizziness, rapid and weak pulse, profuse sweating, brief hypotension, dyspnea, and cyanosis.
Pain, swelling, and tenderness at the injection site may occur.
The possibility of allergic sensitivity, including an anaphylactoid reaction, should be kept in mind.
Infrequently, usually after repeated injection, erythematous, indurated, pruritic plaques have occurred; rarely, these have progressed to scleroderma-like lesions that have persisted for long periods. In other cases, these lesions have resembled erythema perstans.
Hyperbilirubinemia has been observed in the newborn following administration of phytonadione. This has occurred rarely and primarily with doses above those recommended. (See PRECAUTIONS, Pediatric Use.)
Tablets
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 administrationof parenteral phytonadione. This has occurred rarely and primarily with doses above those recommended.
OVERDOSAGE:
Injection: The intravenous LD50 of vitamin K in the mouse is 41.5 and 52 ml/kg for the 0.2% and 1% concentrations respectively.
Tablets: The intravenous and oral LD50s in the mouse are approximately 1.17 g/kg and greater than 24.18 g/kg, respectively.
DOSAGE AND ADMINISTRATION:
Injection
Whenever possible, vitamin K should be given by the subcutaneous or intramuscular route. When intravenous administration is considered unavoidable, the drug should be injected very slowly, not exceeding 1 mg per minute.
Protect from light at all times.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Directions for Dilution
Vitamin K may be diluted with 0.9% sodium chloride injection, 5% dextrose injection, or 5% dextrose and sodium chloride injection. Benzyl alcohol as a preservative has been associated with toxicity in newborns. Therefore, all of the above diluents should be preservative-free (see WARNINGS). Other diluents should not be used. When dilutions are indicated, administration should be started immediately after mixture with the diluent, and unused portions of the dilution should be discarded, as well as unused contents of the ampul.
Prophylaxis of Hemorrhagic Disease of the Newborn
The American Academy of Pediatrics recommends that vitamin K1 be given to the newborn. A single intramuscular dose of vitamin K 0.5 to 1 mg within one hour of birth is recommended.
Treatment of Hemorrhagic Disease of the Newborn
Empiric administration of vitamin K1 should not replace proper laboratory evaluation of the coagulation mechanism. A prompt response (shortening of the prothrombin time in 2 to 4 hours) following administration of vitamin K1 is usually diagnostic of hemorrhagic disease of the newborn, and failure to respond indicates another diagnosis or coagulation disorder.
Vitamin K 1 mg should be given either subcutaneously or intramuscularly. Higher doses may be necessary if the mother has been receiving oral anticoagulants.
Whole blood or component therapy may be indicated if bleeding is excessive. This therapy, however, does not correct the underlying disorder and vitamin K should be given concurrently.
Anticoagulant-Induced Prothrombin Deficiency in Adults
To correct excessively prolonged prothrombin time 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 6 to 8 hours after parenteral administration the prothrombin time has not been shortened satisfactorily, the dose should be repeated (see TABLE 1).
TABLE 1 Vitamin K Summary of Dosage Guidelines
Newborns
Dosage
Hemorrhagic Disease of the Newborn
Prophylaxis
0.5 - 1 mg IM within 1 hour of birth
Treatment
1 mg SC or IM (Higher doses may be necessary if the mother has been receiving oral anticoagulants)
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 synthesis)
2.5 mg - 25 mg or more (rarely up to 50 mg)
In the event of shock or excessive blood loss, the use of whole blood or component therapy is indicated.
Hypoprothrombinemia Due to Other Causes in Adults
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.
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 vitamin K. The severity of the coagulation disorder should determine whether the immediate administration of vitamin K is required in addition to discontinuation or reduction of interfering drug.
Tablets
TALBE 2 Summary of Tablet Dosage Guideline
Adults
Initial Dosage
Anticoagulant-Induced prothrombin deficiency (caused by coumarin or indanedione derivative)
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 synthesis)
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 vitamin K. The severity of the coagulation disorder should determine whether the immediate administration of vitamin K 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 serverity 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.