Usage
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Menadione, also known as Vitamin K3, is a synthetic form of Vitamin K. It’s primarily indicated for the prevention and treatment of hypoprothrombinemia (a deficiency of prothrombin, a clotting factor) caused by Vitamin K deficiency. It is also used in the prevention of anticoagulant-induced prothrombin deficiency. It’s crucial to remember that Menadione is not a nutritional supplement form of Vitamin K for humans due to potential toxicity.
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Pharmacological classification: Vitamin K analog, Hemostatic agent
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Mechanism of action: Menadione is a fat-soluble vitamin precursor. It’s essential for the hepatic synthesis of coagulation factors II, VII, IX, and X, as well as anticoagulant proteins C and S. It acts as a cofactor for the enzyme gamma-glutamyl carboxylase, which converts glutamic acid residues in precursor proteins into gamma-carboxyglutamic acid (Gla) residues. These Gla residues enable the clotting factors to bind calcium ions, which is necessary for their activation and participation in the coagulation cascade.
Alternate Names
- Vitamin K3
- Menadione sodium bisulfite (water-soluble form)
How It Works
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Pharmacodynamics: Menadione promotes blood clotting by facilitating the synthesis of essential clotting factors. Its effect is observed through a decrease in prothrombin time (PT) and international normalized ratio (INR), indicating improved coagulation.
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Pharmacokinetics: Menadione is absorbed from the gastrointestinal tract and requires bile salts for optimal absorption. The water-soluble form (menadione sodium bisulfite) is administered parenterally and bypasses this requirement. It’s primarily metabolized in the liver and excreted in bile and urine. The half-life is not clinically established.
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Mode of action: Menadione undergoes reduction to menaquinone, active form in the liver. It then serves as a cofactor for the gamma-glutamyl carboxylase enzyme, which carboxylates specific glutamic acid residues within the precursor molecules of clotting factors.
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Receptor binding/enzyme inhibition: Menadione does not directly bind to receptors but acts as a cofactor for gamma-glutamyl carboxylase.
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Elimination pathways: Menadione is eliminated through hepatic metabolism and biliary/renal excretion.
Dosage
Standard Dosage
Adults:
- For severe hypoprothrombinemia: 2.5-10 mg IM or IV daily. Oral administration: 10 mg 3-4 times/day.
Children:
- Infants (for vitamin K deficiency): 1-5 mcg/kg/day orally.
Special Cases:
- Elderly Patients: Initiate therapy at the lower end of the dosing range.
- Patients with Renal Impairment: Caution is advised; dose adjustment may be necessary.
- Patients with Hepatic Dysfunction: Caution is advised; dose adjustment may be necessary.
Clinical Use Cases
- The provided sources do not offer dosage recommendations for the specified clinical scenarios (intubation, surgical procedures, etc.) for Menadione. Its primary use is for Vitamin K deficiency. Consult hematology specialist for specific dosing guidance in these contexts.
Dosage Adjustments
Dose modification might be necessary in patients with renal or hepatic impairment. Monitor PT/INR and adjust doses accordingly.
Side Effects
Common Side Effects
- Facial flushing
- Sweating
- Altered taste
- Injection site reactions (pain, redness, swelling)
Rare but Serious Side Effects
- Hemolytic anemia (especially in newborns and patients with G6PD deficiency)
- Kernicterus (brain damage in newborns due to severe hyperbilirubinemia)
- Liver damage (with high doses or prolonged use)
- Allergic reactions (rash, itching, swelling)
Long-Term Effects
- Liver and kidney damage (with prolonged high-dose therapy)
Contraindications
- Hypersensitivity to Menadione or any components of the formulation
- Neonates (especially premature infants)
- G6PD deficiency
- Cholestatic liver disease
Drug Interactions
- Anticoagulants (warfarin, coumarins): Menadione may reduce their effectiveness, increasing the risk of thromboembolic events.
- Orlistat: May decrease Menadione absorption.
- Drugs metabolized by the liver (anticonvulsants, antibiotics): Monitor for potential interactions.
Pregnancy and Breastfeeding
- Menadione is not recommended during pregnancy unless absolutely necessary due to potential risks to the fetus (hemolytic anemia, hyperbilirubinemia, kernicterus).
- Menadione use while breastfeeding is not recommended due to the unknown effects on the infant.
Drug Profile Summary
- Mechanism of Action: Vitamin K analog that promotes hepatic synthesis of coagulation factors II, VII, IX, and X.
- Side Effects: Facial flushing, sweating, altered taste, injection site reactions, hemolytic anemia, kernicterus, liver damage, allergic reactions.
- Contraindications: Hypersensitivity, neonates, G6PD deficiency, cholestatic liver disease.
- Drug Interactions: Anticoagulants, Orlistat, hepatic metabolism drugs.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Varies by indication and patient factors.
- Monitoring Parameters: Prothrombin time (PT), International normalized ratio (INR), liver function tests, kidney function tests.
Popular Combinations
No specific popular drug combinations are commonly associated with menadione.
Precautions
- Patients with liver or kidney disease should be monitored closely.
- Allergic reactions can occur.
- Avoid using in newborns and individuals with G6PD deficiency.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Menadione?
A: The dosage varies depending on the indication and the patient’s age and health status. Refer to the Dosage section for specific guidelines.
Q2: What are the serious side effects of Menadione?
A: Serious side effects include hemolytic anemia (especially in newborns and G6PD deficient individuals), liver damage, and allergic reactions.
Q3: Can Menadione be used during pregnancy?
A: Menadione is generally avoided during pregnancy due to potential fetal risks, including hemolytic anemia and kernicterus.
Q4: Is Menadione safe for breastfeeding mothers?
A: Menadione is not recommended during breastfeeding because its effects on infants are unknown.
Q5: How does Menadione interact with anticoagulants?
A: Menadione can counteract the effects of anticoagulants like warfarin, potentially increasing the risk of blood clots.
Q6: What conditions is Menadione used to treat?
A: Menadione is used for the prevention and treatment of hypoprothrombinemia due to Vitamin K deficiency.
Q7: Who should not take Menadione?
A: Menadione is contraindicated in neonates, individuals with G6PD deficiency, and those with cholestatic liver disease.
Q8: What are the common side effects of Menadione?
A: Common side effects include facial flushing, sweating, altered taste, and injection site reactions.
Q9: How is Menadione administered?
A: Menadione can be administered orally or parenterally (IM, IV, or SC). The route of administration depends on the specific formulation and the patient’s condition.
