Usage
Phytomenadione, also known as Vitamin K1, is a fat-soluble vitamin crucial for the synthesis of specific clotting factors in the liver. It is prescribed for:
- Prevention and treatment of Vitamin K Deficiency Bleeding (VKDB) in newborns. VKDB is a serious condition that can cause uncontrolled internal bleeding.
- Reversal of warfarin overdose or anticoagulation. Warfarin inhibits the synthesis of vitamin K-dependent clotting factors. Phytomenadione counteracts warfarin by providing the necessary vitamin K for clotting factor production.
- Treatment of bleeding or risk of bleeding in patients with conditions or drug therapies affecting vitamin K absorption or synthesis (e.g., liver disease, cystic fibrosis, prolonged use of antibiotics, and some anticonvulsants).
- Hypoprothrombinemia, a deficiency of prothrombin (clotting factor II), which can result from various causes, including vitamin K deficiency.
Pharmacological Classification: Vitamin, Antihemorrhagic
Mechanism of Action: Phytomenadione is a cofactor for the enzyme gamma-glutamyl carboxylase, which is essential for converting precursor proteins into active clotting factors II, VII, IX, and X. These factors are crucial for the coagulation cascade, preventing excessive bleeding. It also activates proteins C and S, which have anticoagulant effects, thus maintaining a balance in the clotting system.
Alternate Names
Brand Names:
- Konakion
- Mephyton
- AquaMephyton
How It Works
Pharmacodynamics: Phytomenadione is essential for the post-translational modification of specific clotting factors (II, VII, IX, and X) and proteins C and S. It facilitates the carboxylation of glutamic acid residues in these proteins, enabling them to bind calcium ions and participate effectively in the coagulation cascade.
Pharmacokinetics:
- Absorption: Administered orally, subcutaneously, intramuscularly (IM), or intravenously (IV). Oral absorption occurs in the small intestine and requires the presence of bile salts. IM administration is generally avoided due to variable absorption and the risk of hematoma. IV administration is preferred in emergency situations.
- Metabolism: Metabolized in the liver, undergoing various transformations.
- Elimination: Excreted mainly in bile and to a lesser extent in urine.
Mode of Action: Phytomenadione acts as a cofactor for gamma-glutamyl carboxylase. This enzyme catalyzes the addition of a carboxyl group to glutamic acid residues in precursor proteins, converting them into active clotting factors and regulatory proteins.
Elimination Pathways: Primarily hepatic metabolism followed by biliary excretion. Some renal excretion occurs.
Dosage
Standard Dosage
Adults:
- VKDB Prophylaxis: Not applicable for adult prophylaxis.
- Reversal of Warfarin: Oral: 2.5-10 mg, depending on the INR. IV: 5-10mg (slow IV infusion over at least 20-30 seconds). Higher doses may be needed in cases of severe bleeding, but warfarin resistance may occur.
- Hypoprothrombinemia: 2.5-25 mg PO/SC/IV/IM. Dose may be repeated every 6-8 hours if necessary.
- Nutritional Supplementation: Males: 120 mcg/day PO. Females: 90 mcg/day PO.
Children:
- VKDB Prophylaxis: IM: 0.5 - 1 mg single dose within one hour of birth. Oral: 2 mg at birth, repeated at 3-7 days and 6 weeks if exclusively breastfed.
- Other indications: Dose individualized based on the condition, severity, and response to treatment. Generally, doses do not exceed 5 mg. IM injection is avoided.
Special Cases:
- Elderly Patients: Lower doses are recommended due to increased sensitivity. Close monitoring is essential.
- Patients with Renal Impairment: No specific dose adjustment, but caution is advised.
- Patients with Hepatic Dysfunction: Dose reduction may be required due to impaired metabolism.
- Patients with Comorbid Conditions: Consider underlying conditions and potential drug interactions.
Clinical Use Cases:
Dosing guidelines are provided in the Standard Dosage and Special Cases section above.
Dosage Adjustments:
Dose adjustments are required for elderly patients, hepatic impairment patients, patients with comorbid conditions, or if drug interactions exist.
Side Effects
Common Side Effects:
- Pain, swelling, redness at the injection site (IM/IV)
- Flushing
- Altered taste (metallic)
- Sweating
Rare but Serious Side Effects:
- Allergic reactions (rash, itching, hives, swelling, difficulty breathing)
- Anaphylaxis
- Hemolytic anemia (in neonates given high doses)
- Kernicterus (bilirubin-induced brain damage in neonates with high doses)
Long-Term Effects:
No specific long-term effects from appropriate usage, but high doses can cause warfarin resistance for an extended period.
Adverse Drug Reactions (ADR):
Anaphylaxis, Hemolytic anemia, Kernicterus
Contraindications:
- Hypersensitivity to phytomenadione or any component of the formulation.
- Severe liver disease (relative contraindication, dose adjustments needed).
- Pre-existing hypercoagulable states (relative contraindication).
Drug Interactions:
- Warfarin: Phytomenadione antagonizes the anticoagulant effects of warfarin.
- Other anticoagulants (e.g., acenocoumarol, phenprocoumon): Interactions similar to warfarin may occur, requiring careful monitoring.
- Orlistat: May decrease vitamin K absorption.
- Cholestyramine, colestipol, colesevelam: May reduce vitamin K absorption.
- Mineral oil: May reduce vitamin K absorption.
- Antibiotics: Prolonged use of certain antibiotics can reduce vitamin K synthesis in the gut.
Pregnancy and Breastfeeding:
- Pregnancy Safety Category: C
- Fetal Risks: Limited human data; generally considered safe, but large doses should be avoided, especially near term.
- Breastfeeding: Excreted in breast milk in small amounts; generally considered safe.
Drug Profile Summary
See above.
Popular Combinations:
- Prothrombin complex concentrate (PCC) in major bleeding due to warfarin overdose.
- Fresh frozen plasma (FFP) as an alternative to PCC.
Precautions:
- General Precautions: Monitor for allergic reactions. Monitor INR regularly when used to reverse warfarin. Check patient medication list for potential interactions.
- Specific Populations: See Special Cases under Dosage.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Phytomenadione?
A: See Dosage section above for detailed information.
Q2: How is Phytomenadione administered?
A: Phytomenadione can be administered orally, subcutaneously, intramuscularly (IM), or intravenously (IV). IM injections are generally avoided due to variable absorption and risk of hematoma formation. IV is preferred in emergency situations.
Q3: How does Phytomenadione reverse warfarin’s effects?
A: Warfarin inhibits the synthesis of vitamin K-dependent clotting factors. Phytomenadione bypasses this inhibition by providing the necessary vitamin K for clotting factor production.
Q4: What are the signs and symptoms of Vitamin K deficiency bleeding (VKDB) in newborns?
A: VKDB can manifest as easy bruising, bleeding from the umbilical cord, gastrointestinal bleeding, intracranial hemorrhage, and prolonged bleeding from minor cuts.
Q5: Can Phytomenadione be used during pregnancy?
A: Phytomenadione is generally considered safe during pregnancy, but large doses should be avoided, especially close to term.
Q6: What are the contraindications for Phytomenadione?
A: Contraindications include hypersensitivity to phytomenadione and severe liver disease (relative contraindication, dose adjustments needed).
Q7: Are there any dietary sources of Vitamin K?
A: Yes, Vitamin K is found in green leafy vegetables, such as spinach, kale, and broccoli, and in some vegetable oils.
Q8: What should be monitored in patients receiving phytomenadione?
A: For patients receiving phytomenadione to reverse warfarin, International Normalized Ratio (INR) should be closely monitored. If administered IM or IV, monitor for signs of allergic reactions. In neonates, monitor for jaundice and signs of hemolysis.
Q9: Does Phytomenadione interact with any other medications?
A: Yes. See the Drug Interactions section. It’s crucial to review the patient’s medication list for potential interactions.
