K-One MM

Approved Indications:

• Vitamin K Deficiency Bleeding (VKDB):
• Prophylaxis and treatment in newborns and infants
• Hypoprothrombinemia due to Vitamin K Deficiency:
• Secondary to long-term use of anticoagulants (e.g., warfarin)
• Secondary to antibiotics, salicylates, sulfonamides, or bile acid sequestrants
• Overdose or Reversal of Oral Anticoagulants (e.g., Warfarin):
• Management of elevated INR without bleeding
• Emergency reversal in cases of major bleeding due to warfarin
• Obstructive Jaundice, Biliary Fistula, or Steatorrhea:
• Where fat-soluble vitamin absorption is impaired

Clinically Accepted Off-Label Uses:

• Vitamin K Deficiency in Chronic Liver Disease:
• Used to support coagulation in hepatic dysfunction
• Preoperative Management in Patients with Anticoagulant Therapy

Adults:

• Warfarin Overdose (Without Bleeding):
• Oral: 1–10 mg based on INR level
• IV: 1–10 mg slowly over at least 30 minutes
• Warfarin Overdose (With Life-Threatening Bleeding):
• IV: 10 mg as a slow infusion along with fresh frozen plasma or prothrombin complex concentrate
• Vitamin K Deficiency:
• Oral/IM/SC: 2.5–25 mg, repeated as necessary
• Usual daily dose: 10–20 mg (depending on severity)

Neonates (Prophylaxis of VKDB):

• IM: 0.5–1 mg once at birth
• Oral: 2 mg at birth, followed by 2 mg at 1 week and 1 month of age

Pediatric Patients (Treatment of Deficiency):

• Oral/IM/IV: 1–5 mg, depending on age, weight, and severity

Elderly:

• Start with the lowest effective dose
• Adjust based on INR monitoring, especially in those on anticoagulants

Renal/Hepatic Impairment:

• No adjustment typically required, but effectiveness may be reduced in severe hepatic dysfunction due to lack of clotting factor synthesis
• Use IV route with caution in hepatic failure patients

Administration Notes:

• IV: Must be administered slowly (≥30 minutes) to avoid anaphylactoid reactions
• IM/SC: Use only when IV or oral routes are not feasible
• Oral: Preferred for non-emergency reversal of anticoagulant therapy

Phytomenadione (Vitamin K1) acts as a cofactor for the hepatic synthesis of active clotting factors II (prothrombin), VII, IX, and X, as well as proteins C and S, all of which are vitamin K-dependent. It enables the γ-carboxylation of glutamic acid residues on these factors, a process essential for their activation and function in the coagulation cascade. In conditions of deficiency or warfarin-induced inhibition, administration of phytomenadione restores normal clotting function by reactivating the vitamin K cycle and promoting production of functional coagulation proteins.

• Absorption:
• Oral absorption is variable; enhanced with dietary fats
• IM and IV forms ensure better bioavailability
• Distribution:
• Widely distributed, especially in the liver
• Highly protein-bound (90%)
• Metabolism:
• Hepatic metabolism via cytochrome P450 enzymes
• Elimination:
• Excreted primarily in bile and feces; minor renal excretion
• Half-life: ~1.5 to 3 hours (may vary by route and dose)
• Onset of Action:
• Oral: ~6–12 hours
• IV: ~1–2 hours
• Full effect on INR: within 24–48 hours

• Pregnancy:
• FDA Category C
• Use only if clearly needed; high doses in late pregnancy may cause jaundice or hemolytic anemia in the newborn
• Commonly used in late pregnancy to prevent hemorrhagic disease of the newborn
• Lactation:
• Considered safe
• Low levels pass into breast milk; does not provide sufficient vitamin K to infants, hence direct supplementation is recommended for newborns

• Primary Class: Hemostatic Agent
• Subclass: Vitamin K (Fat-soluble vitamin)
• Other Classification: Antidote for anticoagulant toxicity

• Known hypersensitivity to phytomenadione or any excipients
• Patients with history of severe allergic reaction to Vitamin K1 (e.g., anaphylaxis)
• Do not use for treatment of severe coagulation disorders due to hepatic failure where synthesis of clotting factors is absent

• Anaphylactoid Reactions (IV Use):
• Risk of severe hypersensitivity and cardiovascular collapse; administer slowly under medical supervision
• Hepatic Disease:
• Ineffective in correcting coagulopathy from hepatic failure due to absence of clotting factor production
• Neonates:
• Avoid high doses; may cause hemolytic anemia or hyperbilirubinemia, particularly in premature infants
• Overcorrection:
• Excessive doses may make re-anticoagulation with warfarin difficult
• IM/SC Routes:
• Use cautiously in patients with bleeding disorders due to risk of hematoma

Common:

• Injection site reactions (pain, swelling)
• Transient flushing or dizziness (IV use)
• Nausea, altered taste

Serious/Rare:

• Anaphylactoid reactions (IV route; rare but potentially fatal)
• Hemolytic anemia (especially in G6PD-deficient infants)
• Hyperbilirubinemia or kernicterus in neonates (high doses)
• Hypotension, dyspnea, chest pain (rapid IV infusion)

• Oral Anticoagulants (Warfarin):
• Antagonizes effect; lowers INR
• Broad-spectrum Antibiotics:
• May impair vitamin K synthesis in the gut, increasing deficiency risk
• Salicylates, Sulfonamides, Anticonvulsants:
• May impair vitamin K activity or absorption
• Cholestyramine or Orlistat:
• Decrease absorption of oral vitamin K
• Enzyme Systems:
• Metabolized by hepatic cytochrome P450 enzymes (exact isoforms not clearly defined)

• INR Management Guidelines (2024):
• Emphasize oral phytomenadione for non-bleeding warfarin reversal over parenteral unless rapid reversal is needed
• Neonatal Guidelines (WHO & AAP):
• Continue to recommend IM vitamin K1 at birth as standard prophylaxis against hemorrhagic disease of the newborn
• Safety Notice:
• IV administration must be slow and diluted to reduce anaphylaxis risk

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Light Sensitivity: Protect from light; amber ampoules or packaging recommended
• Handling:
• Do not freeze
• Shake oral solutions well before use
• Discard unused solution from ampoules after opening