Phytonadione

Vitamin K Fat-soluble vitamin

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO (oral) 2.5-5 mg/kg q12h (every 12 hours) Duration: Variable; for rodenticide toxicosis, typically 3-6 weeks depending on the anticoagulant's half-life. For warfarin, 1-2 weeks; for long-acting (brodifacoum, bromadiolone), 4-6 weeks.
Notes: Administer with a fatty meal to enhance absorption. Monitor PT/PTT every 48-72 hours. If vomiting, use SC route.
Dog SC (subcutaneous) 2.5-5 mg/kg q12h Duration: Same as oral; transition to oral when possible.
Notes: Use small-gauge needle; massage injection site. Avoid IM due to risk of hematoma.
Cat PO (oral) 2.5-5 mg/kg q12h Duration: Same as dog; for rodenticide toxicosis, 3-6 weeks.
Notes: Administer with food. Monitor PT.
Cat SC (subcutaneous) 2.5-5 mg/kg q12h Duration: Same as oral; transition when stable.
Notes: Use caution in cats with hepatic disease.
Horse PO (oral) 0.5-1 mg/kg q24h Duration: For sweet clover disease, 1-2 weeks or until PT normalizes.
Notes: May require higher doses in severe toxicity.
Horse IV (intravenous) 0.5-1 mg/kg q24h Duration: For emergency; slow IV infusion.
Notes: IV use may cause anaphylactoid reactions; use with caution.
Cattle PO (oral) 1-2 mg/kg q24h Duration: For sweet clover disease, 1-2 weeks.
Notes: May be administered in feed or as drench.
Cattle SC (subcutaneous) 1-2 mg/kg q24h Duration: Same as oral.
Notes: Use aseptic technique.
Small Ruminants (sheep/goats) PO (oral) 1-2 mg/kg q24h Duration: For sweet clover disease, 1-2 weeks.
Notes: Monitor PT.
Rabbit PO (oral) 2-5 mg/kg q12h Duration: For rodenticide toxicosis, 3-6 weeks.
Notes: Administer with a small amount of high-fat food (e.g., peanut butter) to enhance absorption.
Bird/Poultry PO (oral) 1-5 mg/kg q12h Duration: For vitamin K deficiency, 1-2 weeks.
Notes: May be added to drinking water for flock treatment.
Exotic (ferret, guinea pig) PO (oral) 2-5 mg/kg q12h Duration: For rodenticide toxicosis, 3-6 weeks.
Notes: Use liquid formulation for accurate dosing.

Clinical Indications & Species Uses

General Indications
  • Treatment and prevention of vitamin K deficiency
  • Anticoagulant rodenticide poisoning
  • Reversal of anticoagulant effect of coumarin derivatives
Dog (Canine)
  • Anticoagulant rodenticide toxicosis (e.g., warfarin, brodifacoum, bromadiolone)
  • Vitamin K deficiency
  • Overdose of coumarin anticoagulants (e.g., warfarin)
  • Treatment of coagulopathy due to liver disease (adjunctive)
Cat (Feline)
  • Anticoagulant rodenticide toxicosis
  • Vitamin K deficiency
  • Overdose of coumarin anticoagulants
Horse (Equine)
  • Anticoagulant rodenticide toxicosis (rare)
  • Vitamin K deficiency
  • Overdose of dicoumarol (sweet clover disease)
Cattle (Bovine)
  • Sweet clover disease (dicoumarol toxicosis)
  • Vitamin K deficiency
  • Anticoagulant rodenticide toxicosis (rare)
Small Ruminants (Sheep / Goat)
  • Sweet clover disease (dicoumarol toxicosis)
  • Vitamin K deficiency
  • Anticoagulant rodenticide toxicosis (rare)
Rabbit & Small Mammals
  • Anticoagulant rodenticide toxicosis
  • Vitamin K deficiency
Avian & Poultry
  • Anticoagulant rodenticide toxicosis (rare)
  • Vitamin K deficiency (e.g., due to coccidiostats or sulfa drugs)
Exotic & Other Species
  • Anticoagulant rodenticide toxicosis in small mammals (e.g., ferrets, guinea pigs)
  • Vitamin K deficiency in reptiles (rare)

Pharmacology & Mechanism of Action

Drug Class: Vitamin K | Pharmacological Group: Fat-soluble vitamin

Mechanism of Action: Phytonadione (vitamin K1) is a fat-soluble vitamin that serves as a cofactor for the hepatic microsomal enzyme gamma-glutamyl carboxylase. This enzyme catalyzes the post-translational carboxylation of glutamic acid residues on vitamin K-dependent clotting factors (II, VII, IX, X) and anticoagulant proteins (proteins C and S). Carboxylation is essential for these proteins to bind calcium and phospholipid membranes, enabling their procoagulant activity. In the setting of vitamin K deficiency or antagonism (e.g., by warfarin or rodenticides), the liver produces nonfunctional clotting factors, leading to coagulopathy. Administration of phytonadione bypasses the block by providing the reduced form of vitamin K, restoring gamma-carboxylation and thus normal hemostasis.

Pharmacodynamics: Phytonadione promotes the synthesis of active clotting factors in the liver. Its effect is not immediate; it requires time for the liver to synthesize and release functional clotting factors. Onset of action is typically 6-12 hours after administration, with normalization of clotting times (PT, aPTT) often seen within 12-24 hours. The drug does not reverse the anticoagulant effect of heparin or direct thrombin inhibitors. In animals with vitamin K-dependent clotting factor deficiency, phytonadione corrects the coagulopathy and prevents further bleeding.

⚑ Pharmacokinetics Summary

Absorption: Phytonadione is well absorbed from the gastrointestinal tract when administered orally, especially when given with food (fat enhances absorption). Absorption is bile-dependent; in animals with biliary obstruction or malabsorption, oral absorption may be erratic. Subcutaneous and intramuscular routes provide reliable absorption. Intravenous administration is reserved for emergencies but carries a risk of anaphylactoid reactions.
Distribution: Phytonadione is highly lipophilic and distributes widely throughout the body. It crosses the placenta and is excreted in milk. It accumulates in the liver, where it exerts its pharmacological effect. Protein binding is high (approximately 90%), primarily to lipoproteins.
Metabolism: Phytonadione is rapidly metabolized in the liver to more polar metabolites, which are then excreted. The metabolic pathway involves side-chain oxidation and glucuronide conjugation.
Excretion: Metabolites are excreted primarily in the bile and feces. A small amount is excreted in the urine. Enterohepatic recirculation may occur.
Half-Life: The half-life in dogs is approximately 4-6 hours; in cats, it is similar. However, the biological effect on clotting factor synthesis lasts longer (24-48 hours).
Bioavailability: Oral bioavailability is variable and depends on bile salts and dietary fat; it is estimated to be 50-80% in healthy animals. Subcutaneous and intramuscular routes provide near-complete bioavailability.
Protein Binding: Approximately 90% bound to lipoproteins.

Available Formulations & Strengths

Oral Tablet 5 mg, 10 mg (PO)
Oral Liquid (drops) 2 mg/mL, 10 mg/mL (PO)
Injectable Solution 2 mg/mL, 10 mg/mL (IV, IM, SC)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to phytonadione or any component of the formulation
  • Severe hepatic disease (may not respond adequately)
  • Coagulopathy due to heparin or direct oral anticoagulants (not effective)
  • Concurrent use of vitamin K antagonists (e.g., warfarin) for therapeutic anticoagulation (unless treating overdose)
Warnings & Clinical Precautions:
  • IV administration should be slow (not exceeding 1 mg/min) and reserved for emergencies due to risk of anaphylactoid reactions (flushing, dyspnea, hypotension, cardiovascular collapse).
  • IM administration may cause hematoma formation in coagulopathic patients; use SC or PO when possible.
  • Oral absorption is dependent on bile salts and dietary fat; administer with food.
  • In animals with biliary obstruction or malabsorption, parenteral administration is preferred.
  • Monitor prothrombin time (PT) and activated partial thromboplastin time (aPTT) to guide therapy.
  • For rodenticide toxicosis, treatment may need to be prolonged (weeks) because long-acting anticoagulants persist in the body.
  • Use with caution in pregnant animals; vitamin K crosses the placenta, but benefits may outweigh risks in life-threatening toxicity.
  • Do not use as an antidote for heparin overdose.
  • In food animals, observe withdrawal times.

Adverse Effects & Reactions

Common:

  • Injection site reactions (pain, swelling)
  • Gastrointestinal upset (vomiting, diarrhea) after oral administration
  • Transient flushing or hypotension after rapid IV administration

Serious / Severe:

  • Anaphylactoid reactions (especially after IV administration)
  • Hemolytic anemia in neonates (especially with large doses)
  • Hyperbilirubinemia in neonates (especially premature infants, but also reported in animals)

Rare:

  • Allergic dermatitis
  • Methemoglobinemia (in neonates)
  • Liver enzyme elevations

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Warfarin and other coumarin anticoagulants Phytonadione antagonizes the anticoagulant effect; used as antidote for overdose. High
Mineral oil or orlistat Reduced absorption of oral phytonadione due to interference with fat absorption. Moderate
Broad-spectrum antibiotics (e.g., cephalosporins, sulfonamides) May reduce vitamin K production by gut flora, potentially increasing vitamin K requirements. Mild
Phenytoin, phenobarbital, or other hepatic enzyme inducers May increase metabolism of vitamin K, reducing its effectiveness. Moderate
Cholestyramine Binds bile acids and reduces absorption of fat-soluble vitamins including vitamin K. Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Hemolytic anemia
  • Hyperbilirubinemia
  • Jaundice
  • Kernicterus (in neonates)
  • Liver dysfunction
  • Hypotension (with rapid IV administration)

Emergency Treatment Protocol: There is no specific antidote for phytonadione overdose. Treatment is symptomatic and supportive. Discontinue the drug. For severe hemolytic reactions, provide supportive care including intravenous fluids, blood transfusion if anemia is severe, and monitoring of bilirubin and liver enzymes. In neonates, exchange transfusion may be considered in severe hyperbilirubinemia. Most cases resolve with discontinuation and supportive care.

Food Animal Withdrawal Times

πŸ₯© Meat: 0 daysπŸ₯› Milk: 0 daysπŸ₯š Eggs: 0 days

Phytonadione is generally considered to have a zero withdrawal time in food animals when used according to label. However, for extra-label use, consult with a veterinarian and follow local regulations. In the US, the FDA has established tolerances for vitamin K in animal tissues, but no withdrawal period is required for approved uses.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (20-25Β°C, 68-77Β°F). Protect from light.

Light Sensitivity: Light-sensitive β€” protect from direct exposure.

Handling & Special Conditions: Keep container tightly closed. Do not freeze. Protect from moisture. Injectable solutions should be stored away from light and used before expiration date.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs and cats for the treatment of anticoagulant rodenticide toxicosis. Also approved for use in horses and food animals for sweet clover disease. Various generic formulations are available.

Extra-Label (Off-Label) Use: In the US, phytonadione is available as a prescription drug for veterinary use. Extra-label use in food animals is permitted under AMDUCA with a valid veterinary-client-patient relationship, but requires a withdrawal time established by the veterinarian. For non-food animals, extra-label use is common.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Phytonadione is the treatment of choice for anticoagulant rodenticide poisoning and sweet clover disease. It is essential to initiate therapy as soon as possible after exposure, but it is not effective for reversing the effects of heparin or direct oral anticoagulants. The route of administration depends on the clinical status: oral is preferred for stable patients, while subcutaneous is used when oral administration is not possible or when rapid absorption is needed. Intravenous administration should be reserved for life-threatening bleeding and must be given slowly to avoid anaphylactoid reactions. Monitoring of clotting times (PT, aPTT) is crucial to guide dosing and duration of therapy. For rodenticide toxicosis, treatment must be continued for weeks because long-acting anticoagulants have a prolonged half-life. Always consider the potential for re-exposure and educate owners about preventing access to rodenticides. In food animals, observe withdrawal times and follow regulatory guidelines.

References & Literature

  • πŸ“š Plumb's Veterinary Drug Handbook
  • πŸ“š Papich Veterinary Pharmacology and Therapeutics
  • πŸ“š Compendium of Veterinary Products (CVP)