PHYTONADIONE, VITAMIN 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 itis quite sensitive to light. If used as an intravenous infusion, the container should be wrapped withan 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 anddiluents used, it is suggested to consult specialized references (e.g., Handbook on Injectable Drugsby Trissel; see bibliography) for more specific information on the compatibility of phytonadionewith other drugs.

Pharmacology - PHYTONADIONE, VITAMIN K1

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 inactiveprecursors 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, VITAMIN K1

Phytonadione is absorbed from the GI tract in monogastric animals via theintestinal lymphatics, but only in the presence of bile salts. Oral absorption of phytonadione may besignificantly enhanced by administering with fatty foods. The relative bioavailability of the drug isincreased 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 storedin the liver or other tissues. Only small amounts are distributed across the placenta in pregnantanimals. Exogenously administered phytonadione enters milk. The elimination of Vitamin K1 is notwell understood.

Contraindications, Precautions, Reproductive Safety

Many veterinary clinicians state that theintravenous use of phytonadione is contraindicated because of increased risk of anaphylaxis development, but intravenous phytonadione is used in human medicine and several intravenous dosageregimens are outlined below in the Dosage section. Phytonadione is contraindicated in patientshypersensitive 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 documentedin pregnant animals.

Adverse Effects, Warnings

Anaphylactoid reactions have been reported following IV administration of Vitamin K1; use with extreme caution (See Contraindications above). Intramuscularadministration may result in acute bleeding from the site of injection during the early stages oftreatment. Small gauge needles are recommended for use when injecting SQ or IM. Subcutaneousinjections 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 phytonadioneadministration, 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 thattoxic symptoms would result after a single overdosage. However, refer to the Adverse Effectssection for more information.

Drug Interactions

As would be expected, phytonadione antagonizes the anticoagulant effects ofcoumarin (e.g., warfarin) and indandione agents.
The following drugs may prolong or enhance the effects of anticoagulants and antagonize some ofthe therapeutic effects of phytonadione: phenylbutazone, aspirin, chloramphenicol, sulfonamides (including trimethoprim-sulfa), diazoxide, allopurinol, cimetidine, metronidazole, anabolic steroids, erythromycin, ketoconazole, propranolol, and thyroiddrugs.
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.