KAPPADIONE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KAPPADIONE (KAPPADIONE).
Provides vitamin K activity necessary for hepatic synthesis of clotting factors II, VII, IX, and X.
| Metabolism | Hepatic; rapidly metabolized via side chain oxidation and conjugation. |
| Excretion | Primarily excreted via bile into feces; minimal renal excretion (<5% unchanged in urine). |
| Half-life | Terminal elimination half-life is approximately 2-3 hours for phylloquinone (K1); clinical effect on clotting factors lasts 24-48 hours due to prolonged hepatic action. |
| Protein binding | Highly protein bound (>99%), primarily to lipoproteins. |
| Volume of Distribution | Vd approximately 0.7-1.0 L/kg, indicating distribution into extravascular tissues, particularly liver. |
| Bioavailability | Oral bioavailability is low and variable (approximately 50% due to limited absorption and first-pass metabolism); IM/IV routes provide 100% bioavailability. |
| Onset of Action | IV: 1-2 hours for reversal of warfarin; IM: 6-10 hours; Oral: 6-12 hours. |
| Duration of Action | Duration of action lasts 24-48 hours for reversal of anticoagulation; longer for synthetic vitamin K analogues (e.g., menadione). |
| Molecular Weight | 450.7 |
Adults: 5-10 mg subcutaneously, intravenously, or intramuscularly once; may repeat in 12-48 hours if needed. For oral anticoagulant reversal: 1-5 mg orally.
| Dosage form | INJECTABLE |
| Renal impairment | No adjustment required for any GFR level; kappadione is hepatically metabolized and not renally excreted. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Use with caution; consider lower initial doses (e.g., 2-5 mg) due to potential coagulation factor synthesis impairment. Child-Pugh Class C: Avoid use unless vitamin K deficiency is confirmed and benefits outweigh risks; if used, monitor INR closely. |
| Pediatric use | Neonates: 0.5-1 mg intramuscularly once at birth. Infants: 1-2 mg intramuscularly or subcutaneously once. Children: 5-10 mg intramuscularly or subcutaneously once; may repeat if needed. Doses based on 0.3-0.6 mg/kg for reversal; maximum 10 mg. |
| Geriatric use | No specific dose adjustment required; but use caution due to higher risk of thromboembolic events and polypharmacy; start at lower end of dosing range (e.g., 1-5 mg orally) and monitor INR. |
| 1st trimester | Phytonadione (vitamin K1) is generally considered safe in the first trimester when used at recommended doses for vitamin K deficiency or reversal of anticoagulation. No teratogenic effects have been documented at therapeutic doses. High doses may be associated with neonatal hemolysis and hyperbilirubinemia. |
| 2nd trimester | Safe in second trimester at recommended doses. No evidence of fetal harm. Use only if clearly indicated. |
| 3rd trimester | Safe in third trimester; used prophylactically to prevent hemorrhagic disease of the newborn. Intravenous administration near term may rarely cause anaphylactoid reactions. |
Clinical note
Comprehensive clinical and safety monograph for KAPPADIONE (KAPPADIONE).
| Placental transfer | Phytonadione crosses the placenta poorly; only small amounts reach the fetal circulation. The degree of transfer is limited and not clinically significant at maternal therapeutic doses. |
| Breastfeeding |
■ FDA Black Box Warning
Intravenous administration has been associated with severe reactions including anaphylaxis, cardiac arrest, and death. Reserve IV use for when other routes are not feasible and have resuscitation equipment available.
| Serious Effects |
Hypersensitivity to phytonadione or any component of the formulationSevere hepatic disease (especially with parenteral administration due to risk of hepatotoxicity)
| Precautions | Risk of severe hypersensitivity reactions with IV use, Not effective for hereditary hypoprothrombinemia, Use with caution in patients with hepatic impairment, Monitor INR during therapy |
| Food/Dietary | High dietary intake of vitamin K-rich foods (e.g., spinach, kale, collard greens, Swiss chard, parsley, broccoli, Brussels sprouts, cabbage, liver, beef, pork, green tea) can antagonize the effects of warfarin. Patients stabilized on phytonadione for warfarin reversal should maintain consistent intake of vitamin K; sudden increases can reduce INR and sudden decreases can increase INR. Alcohol consumption may interfere with vitamin K metabolism and anticoagulation control. |
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| Phytonadione is excreted into breast milk in minimal amounts. The oral absorption of vitamin K in infants is poor, so it is unlikely to cause adverse effects in breastfed infants. It is considered compatible with breastfeeding. Use with caution if infant has glucose-6-phosphate dehydrogenase deficiency. |
| Lactation Rating | L1 (Safe) |
| Teratogenic Risk | KAPPADIONE (phytonadione) is a synthetic form of vitamin K. There are no well-controlled studies in pregnant women. Animal reproduction studies have not been conducted. Vitamin K is essential for the synthesis of clotting factors; deficiency can lead to fetal bleeding. The drug should be used during pregnancy only if clearly needed. There is no evidence of teratogenicity from the limited human data, but theoretical risks exist from the preservative benzyl alcohol in some parenteral formulations, associated with gasping syndrome in neonates. |
| Fetal Monitoring | Monitor maternal prothrombin time and INR to ensure adequate dosing. In neonates of mothers receiving high doses, monitor for signs of hyperbilirubinemia and hemolytic anemia due to potential oxidant stress from the preservative benzyl alcohol. No specific fetal monitoring required beyond routine prenatal care. |
| Fertility Effects | No known adverse effects on fertility. Vitamin K is a fat-soluble vitamin essential for normal reproductive function; deficiency may impair fertility, but supplementation at recommended doses does not impair fertility. |
| Clinical Pearls | Phytonadione (vitamin K1) is preferred over menadione for anticoagulant reversal due to lower risk of hemolysis. Onset of action for INR correction is 6-12 hours intravenously (slow IV infusion, no faster than 1 mg/min) and 24-48 hours orally. Anaphylactoid reactions can occur with IV administration; have resuscitation equipment available. Monitor INR daily after administration. In warfarin overdose with significant bleeding, use prothrombin complex concentrate (PCC) or fresh frozen plasma (FFP) in addition to vitamin K. Not effective for reversal of direct oral anticoagulants (DOACs). |
| Patient Advice | Take phytonadione exactly as prescribed; do not miss doses or change frequency without consulting your doctor. · Report any signs of allergic reaction (rash, itching, swelling, severe dizziness, trouble breathing) especially after IV administration. · Avoid large amounts of foods high in vitamin K (e.g., leafy greens: spinach, kale, broccoli, Brussels sprouts; liver; green tea) if you are on warfarin, as they can decrease the effectiveness of the anticoagulant. Keep vitamin K intake consistent. · Phytonadione is used to treat bleeding problems due to low vitamin K levels or to reverse the effects of blood thinners like warfarin. It will not reverse the effects of other blood thinners (e.g., rivaroxaban, apixaban). · Do not use this medication for purposes other than prescribed. Seek immediate medical help for uncontrolled bleeding. |