2.1 Dosing Considerations

Whenever possible, administer Vitamin K1 Injection by the subcutaneous route [see Boxed Warning]. When intravenous administration is unavoidable, inject the drug very slowly, not exceeding 1 mg per minute [see Warnings and Precautions (5.1)].

Monitor international normalized ratio (INR) regularly and as clinical conditions indicate. Use the lowest effective dose of Vitamin K1 Injection.

The coagulant effects of Vitamin K1 Injection are not immediate; improvement of INR may take 1 to 8 hours. Interim use of whole blood or component therapy may also be necessary if bleeding is severe.

Whenever possible, administer benzyl alcohol-free phytonadione formulations in pediatric patients [see Warnings and Precautions (5.2), Use in Specific Populations (8.4)].

When Vitamin K1 Injection is used to correct excessive anticoagulant-induced hypoprothrombinemia, anticoagulant therapy still being indicated, the patient is again faced with the clotting hazards existing prior to starting the anticoagulant therapy. Vitamin K1 Injection is not a clotting agent, but overzealous therapy with Vitamin K1 Injection may restore conditions which originally permitted thromboembolic phenomena. Dosage should be kept as low as possible, and INR should be checked regularly as clinical conditions indicate.

2.2 Recommended Dosage for Coagulation Disorders from Vitamin K Deficiency or Interference

The recommended dosage of Vitamin K1 Injection is based on whether the hypoprothrombinemia is anticoagulant-induced (e.g., due to coumarin or indanedione derivatives) or non-anticoagulant-induced (e.g., due to antibiotics; salicylates or other drugs; factors limiting absorption or synthesis) as follows:

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Anticoagulant-Induced Hypoprothrombinemia: Vitamin K1 Injection 2.5 mg to 10 mg or more subcutaneously, intramuscularly, or intravenously. Up to 25 mg to 50 mg may be administered as a single dose.

Repeated large doses of Vitamin K1 Injection are not warranted in liver disease if the initial response is unsatisfactory. Failure to respond to Vitamin K1 Injection may indicate that the condition being treated is inherently unresponsive to Vitamin K1 Injection.

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Hypoprothrombinemia Due to Other Causes (Non-Anticoagulation-Induced Hypoprothrombinemia): Vitamin K1 Injection 2.5 mg to 25 mg or more intravenously, intramuscularly, or subcutaneously. Up to 50 mg may be administered as a single dose.

Evaluate INR after 6 to 8 hours, and repeat dose if INR remains prolonged. Modify subsequent dosage (amount and frequency) based on the INR or clinical condition.

2.3 Recommended Dosage for Prophylaxis and Treatment of Vitamin K Deficiency Bleeding in Neonates

Prophylaxis of Vitamin K-Deficiency Bleeding in Neonates

The recommended dosage of Vitamin K1 Injection is 0.5 mg to 1 mg within one hour of birth for a single dose.

Treatment of Vitamin K Deficiency Bleeding in Neonates

The recommended dosage of Vitamin K1 Injection is 1 mg given either subcutaneously or intramuscularly. Consider higher doses if the mother has been receiving oral anticoagulants.

A failure to respond (shortening of the INR in 2 to 4 hours) may indicate another diagnosis or coagulation disorder.

2.4 Directions for Dilution

Dilute Vitamin K1 Injection with 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or 5% Dextrose and Sodium Chloride Injection. Avoid use of other diluents that may contain benzyl alcohol, which can cause serious toxicity in newborns or low birth weight infants [see Warnings and Precautions (5.2), Use in Specific Populations (8.4)].

When diluted, start administration of Vitamin K1 Injection immediately after dilution. Discard unused portions of diluted solution as well as unused contents of the ampul.

Protect Vitamin K1 Injection from light at all times.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.