MEPHYTON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MEPHYTON (MEPHYTON).
Phytonadione (vitamin K1) is a cofactor for the hepatic microsomal enzyme gamma-glutamyl carboxylase, which catalyzes the posttranslational carboxylation of glutamic acid residues to gamma-carboxyglutamic acid (Gla) on vitamin K-dependent clotting factors (II, VII, IX, X) and anticoagulant proteins (protein C, protein S). Carboxylation enables calcium-mediated binding to phospholipid membranes, essential for hemostatic activity.
| Metabolism | Phytonadione is rapidly metabolized in the liver via side-chain oxidation and conjugation. The metabolic enzymes include cytochrome P450 (CYP4F2) for oxidation and glucuronosyltransferases for conjugation. Metabolites are excreted in urine and bile. |
| Excretion | Primarily hepatic metabolism; minimal renal excretion (<5% unchanged); biliary/fecal excretion of metabolites accounts for ~50%. |
| Half-life | Terminal elimination half-life is approximately 25-33 hours in adults; clinical reversal of warfarin effect occurs within 6-12 hours following IV administration. |
| Protein binding | Greater than 90%; bound primarily to lipoproteins. |
| Volume of Distribution | 0.14-0.2 L/kg; small Vd reflecting limited extravascular distribution, consistent with its fat-soluble nature and hepatic uptake. |
| Bioavailability | Oral: ~50% (low due to bile-dependent absorption); IM and IV: 100%. |
| Onset of Action | IV: Rapid (within 1-2 hours for reversal of anticoagulation); IM: 1-2 hours; Oral: 6-12 hours. |
| Duration of Action | Duration of anticoagulant reversal: 24-48 hours; larger doses (e.g., >10 mg) can prolong effect up to several days; repeated dosing may be needed for sustained reversal. |
For anticoagulant-induced prothrombin deficiency: 1 to 10 mg orally, intravenously, or subcutaneously. Intravenous administration rate not to exceed 1 mg per minute.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment. Phytonadione is not significantly renally eliminated. |
| Liver impairment | No specific dose adjustment issued for hepatic impairment; caution advised in severe hepatic disease as response may be diminished. |
| Pediatric use | Neonates: 0.5 to 1 mg intramuscularly within 1 hour of birth (prophylaxis). For deficiency: 1 to 2 mg orally or subcutaneously. Older children: 5 to 10 mg orally or intravenously. |
| Geriatric use | No specific dose adjustment; use lowest effective dose. Monitor for hypersensitivity reactions and prothrombin time. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MEPHYTON (MEPHYTON).
| Breastfeeding | Vitamin K1 is excreted into breast milk in low amounts. The M/P ratio is approximately 0.1. Standard maternal doses (e.g., 1-5 mg) are considered safe during breastfeeding and do not pose a risk to the infant. The infant's vitamin K status may be supported by colostrum, but neonatal prophylaxis is recommended separately. |
| Teratogenic Risk | Mephyton (phytonadione, vitamin K1) is not teratogenic at therapeutic doses. Vitamin K is essential for fetal coagulation factor synthesis. Maternal deficiency may cause fetal hemorrhage, but pharmacologic doses do not increase congenital malformations. However, large doses (e.g., menadione, a synthetic analog) in third trimester have been associated with hemolytic anemia and hyperbilirubinemia in neonates, especially in premature infants. Mephyton is considered low risk when used appropriately. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to phytonadione or any component of the formulation. Severe hepatic disease (relative contraindication due to inability to synthesize coagulation factors even with vitamin K).
| Precautions | Intravenous administration should be reserved for severe hemorrhage due to risk of anaphylactoid reactions (including shock and cardiac/respiratory arrest). Rapid IV infusion may cause flushing, dyspnea, and hypotension. Protect parenteral solution from light. Use with caution in patients with hepatic disease (may reduce efficacy). Monitor INR closely when reversing anticoagulation to avoid hypercoagulable state (e.g., warfarin resistance). |
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| Fetal Monitoring | Monitor maternal prothrombin time and INR if treating coagulopathy. In pregnancy, assess fetal growth and anatomy via ultrasound as indicated by maternal condition. No specific fetal monitoring for phytonadione is required beyond routine obstetric care. Monitor newborn for signs of bleeding if mother has vitamin K deficiency. |
| Fertility Effects | Therapeutic doses of phytonadione have no known adverse effects on fertility. Vitamin K is not involved in reproductive hormone pathways. Deficiency may impair fertility due to underlying conditions, but supplementation does not enhance fertility. |