Phytonadione (Vit K1)
Chemistry - A naphthoquinone derivative identical to naturally occurring vitamin K1, phytonadione occurs as a clear, yellow to amber, viscous liquid. It is insoluble in water, slightly soluble in alcohol and soluble in lipids. Phytonadione may also be known as Vitamin K1 , phylloquinone , or phytomenadione .
Storage/Stability/Compatibility - Phytonadione should be protected from light at all times, as it is quite sensitive to light. If used as an intravenous infusion, the container should be wrapped with an opaque material. Tablets and capsules should be stored in well-closed, light-resistant containers.
Because most veterinary clinicians state that phytonadione is contraindicated for intravenous use, and since compatibility is dependent upon factors such as pH, concentration, temperature and diluents used, it is suggested to consult specialized references (e.g., Handbook on Injectable Drugs by Trissel; see bibliography) for more specific information on the compatibility of phytonadione with other drugs.
Pharmacology - Vitamin K1 is necessary for the synthesis of blood coagulation factors II, VII, IX, and X in the liver. It is believed that Vitamin K1 is involved in the carboxylation of the inactive precursors of these factors to form active compounds.
Uses/Indications - The principal uses of exogenously administered phytonadione is in the treatment of anticoagulant rodenticide toxicity. It is also used for treating dicumarol toxicity associated with sweet clover ingestion in ruminants, sulfaquinoxaline toxicity, and in bleeding disorders associated with faulty formation of vitamin K-dependent coagulation factors.
Pharmacokinetics - Phytonadione is absorbed from the GI tract in monogastric animals via the intestinal lymphatics, but only in the presence of bile salts. Oral absorption of phytonadione may be significantly enhanced by administering with fatty foods. The relative bioavailability of the drug is increased 4-5 times in dogs given canned dog food with the dose. After oral administration, increases in clotting factors may not occur until 6-12 hours later.
Phytonadione may concentrate in the liver for a short period of time, but is not appreciably stored in the liver or other tissues. Only small amounts are distributed across the placenta in pregnant animals. Exogenously administered phytonadione enters milk. The elimination of Vitamin K1 is not well understood.
Contraindications/Precautions/Reproductive Safety - Many veterinary clinicians state that the intravenous use of phytonadione is contraindicated because of increased risk of anaphylaxis development, but intravenous phytonadione is used in human medicine and several intravenous dosage regimens are outlined below in the Dosage section. Phytonadione is contraindicated in patients hypersensitive to it or any component of its formulation.
Vitamin K does not correct hypoprothrombinemia due to hepatocellular damage.
Phytonadione crosses the placenta only in small amounts, but its safety has not been documented in pregnant animals.
Adverse Effects/Warnings - Anaphylactoid reactions have been reported following IV administration of Vitamin K1; use with extreme caution (See Contraindications above). Intramuscular administration may result in acute bleeding from the site of injection during the early stages of treatment. Small gauge needles are recommended for use when injecting SQ or IM. Subcutaneous injections or oral dosages may be slowly or poorly absorbed in animals that are hypovolemic.
Because 6-12 hours may be required for new clotting factors to be synthesized after phytonadione administration, emergency needs for clotting factors must be provided for by giving blood products.
Overdosage/Acute Toxicity - Phytonadione is relatively non-toxic, and it would be unlikely that toxic symptoms would result after a single overdosage. However, refer to the Adverse Effects section for more information.
Drug Interactions - As would be expected, phytonadione antagonizes the anticoagulant effects of coumarin (e.g., warfarin) and indandione agents. The following drugs may prolong or enhance the effects of anticoagulants and antagonize some of the therapeutic effects of phytonadione: phenylbutazone, aspirin, chloramphenicol, sulfonamides (including trimethoprim-sulfa), diazoxide, allopurinol, cimetidine, metronidazole, anabolic steroids, erythromycin, ketoconazole, propranolol, and thyroid drugs. Concomitant administration of Mineral Oil may reduce the absorption of oral vitamin K. Although chronic antibiotic therapy should have no significant effect on the absorption of phytonadione, these drugs may decrease the numbers of vitamin K producing bacteria in the gut.
For warfarin (or related compounds) toxicity:
a) 500 mg SQ q4-6h until one-stage prothrombin time (OSPT) returns to normal control values. Whole blood or fresh plasma may also be necessary early in the course of treatment. (Byars 1987)
b) 0.5 - 2.5 mg/kg IM, if IV use is necessary (avoid if possible), dilute in saline or D5W/saline and give very slowly (not to exceed 5 mg/minute). (Upson 1988)
c) For acute hypoprothrombinemia with hemorrhage: 0.5 - 2.5 mg/kg IV, not to exceed 10 mg/minute in mature animals and 5 mg/minute in newborn and very young animals.
For non-acute hypoprothrombinemia: 0.5 - 2.5 mg/kg IM or SQ (Label directions; Veda-K1®—Vedco)
Monitoring Parameters -
1) Clinical efficacy (lack of hemorrhage)
2) One-stage prothrombin time (OSPT)
Client Information - Because it may take several weeks to eliminate some of the anticoagulant rodenticides from the body, clients must be counseled on the importance of continuing to administer the drug (phytonadione) for as long as instructed or renewed bleeding may occur. Unless otherwise instructed, oral phytonadione should be administered with food, preferably foods high in fat content. During therapy, animals should be kept quiet whether at home or hospitalized.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Phytonadione Oral Capsules 25 mg; Veta-K1 ® (PVL; Vedco); (Rx) Approved for use in dogs and cats.
Phytonadione Aqueous Colloidal Solution for Injection 10 mg/ml in 30 ml and 100 ml vials; Veda-K1® (Vedco); (Rx) Approved for use dogs, cats, cattle, calves, horses, swine, sheep, and goats. No withdrawal times listed.
Phytonadione Oral Tablets 5 mg; Mephyton ® (Merck); (Rx)
Phytonadione Injection 2 mg/ml (aqueous colloidal solution) in 0.5 ml amps and syringes and 10 mg/ml (aqueous dispersion) in 1 ml amps and 2.5 & 5 ml vials
Aqua-Mephyton (Merck); Generic (IMS); (Rx)
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