VITAMIN K1
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VITAMIN K1 (VITAMIN K1).
Vitamin K1 (phytonadione) is a fat-soluble vitamin that serves as a cofactor for the enzyme gamma-glutamyl carboxylase, which catalyzes the carboxylation of glutamic acid residues to gamma-carboxyglutamic acid (Gla) on vitamin K-dependent proteins, including clotting factors II, VII, IX, X, and proteins C and S. This carboxylation is essential for their calcium-binding activity and subsequent activation in the coagulation cascade.
| Metabolism | Vitamin K1 is metabolized in the liver via the vitamin K cycle, which involves reduction by vitamin K epoxide reductase (VKOR) and other reductases, followed by reoxidation. The side chain undergoes oxidation and conjugation, with metabolites excreted in bile and urine. |
| Excretion | Primarily hepatic metabolism, with metabolites excreted in bile and feces (up to 60-80%). Renal excretion of metabolites accounts for <10% of the dose. |
| Half-life | Terminal elimination half-life is approximately 2-3 hours for vitamin K1 oxide, but the pharmacodynamic half-life of clotting factor synthesis is 12-24 hours due to prolonged hepatic effects. |
| Protein binding | Highly protein bound (>90%), primarily to lipoproteins and albumin. |
| Volume of Distribution | Approximately 0.15-0.3 L/kg, reflecting distribution primarily to the liver and limited extravascular binding. |
| Bioavailability | Oral bioavailability is approximately 50% (range 20-80%) due to limited absorption and first-pass metabolism; intramuscular bioavailability is variable and not recommended; subcutaneous bioavailability is also poor and unreliable. |
| Onset of Action | IV: 1-2 hours for partial correction of INR; oral: 6-12 hours; subcutaneous: 6-24 hours (variable absorption). |
| Duration of Action | Lasts 24-48 hours after IV or oral administration, with sustained reversal of anticoagulation effect for up to 2-3 days after large doses. |
10 mg IV or IM as a single dose for anticoagulant reversal; may repeat every 12-24 hours as needed. For vitamin K deficiency: 2.5-10 mg PO, IM, or IV once daily.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No specific dose adjustment recommended for hepatic impairment; use standard dosing with monitoring of INR. |
| Pediatric use | For anticoagulant reversal: 0.5-2 mg IV or IM as a single dose. For prophylaxis of hemorrhagic disease of newborn: 0.5-1 mg IM within 1 hour of birth. |
| Geriatric use | No specific dose adjustment required; use standard adult dosing with caution due to potential increased sensitivity to anticoagulant reversal. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VITAMIN K1 (VITAMIN K1).
| Breastfeeding | Vitamin K1 is excreted into breast milk in small amounts; M/P ratio approximately 0.3. No adverse effects reported in nursing infants. Considered compatible with breastfeeding. Supplementation may be required for infants to prevent hemorrhagic disease of newborn if maternal intake low. |
| Teratogenic Risk | Vitamin K1 is considered safe in pregnancy at recommended doses. No evidence of teratogenicity or fetotoxicity in first, second, or third trimesters. High doses (e.g., >5 mg/day) near term may theoretically increase risk of neonatal hyperbilirubinemia or hemolytic anemia, but risk is low. |
■ FDA Black Box Warning
Intravenous administration of vitamin K1 has been associated with severe reactions, including anaphylaxis, cardiac arrest, and death. Therefore, intravenous use should be reserved for serious or life-threatening situations and should be administered with extreme caution.
| Serious Effects |
["Hypersensitivity to vitamin K1 or any component of the formulation"]
| Precautions | ["Severe hypersensitivity reactions (including anaphylaxis) have occurred, particularly with intravenous administration","Intravenous administration may cause hypotension, cyanosis, and bronchospasm","Use in neonates: Intramuscular route is preferred; intravenous use may cause hyperbilirubinemia and kernicterus","Monitor coagulation parameters (INR) when used for warfarin reversal","Effect may be delayed; additional doses may be needed for full reversal"] |
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| Fetal Monitoring | No specific maternal or fetal monitoring required. Monitor for signs of allergic reaction (rare) or hemolytic effects in neonates if high doses administered near delivery. In preterm infants, monitor liver function and coagulation parameters if used therapeutically. |
| Fertility Effects | No known adverse effects on fertility. Vitamin K1 plays a role in bone metabolism and coagulation but no established impact on reproductive function. |