Phytonadione -vitamin K

Phytonadione (Vitamin K)

Usual Diluents

Standard Dilutions   [Amount of drug] [Infusion volume] [Infusion rate]

Elevated INRs (See below)

Elevated INR's

>>>For patients with INRs of > or = 5.0 but < 9.0 and no significant bleeding, we recommend omitting the next one or two doses, monitoring more frequently, and resuming therapy at an appropriately adjusted dose when the INR is at a therapeutic level (Grade 1C). Alternatively, we suggest omitting a dose and administering vitamin K (1 to 2.5 mg) orally, particularly if the patient is at increased risk of bleeding (Grade 2A). If more rapid reversal is required because the patient requires urgent surgery, we suggest vitamin K  (< or = 5 mg) orally, with the expectation that a reduction of the INR will occur in 24 h. If the INR is still high, we suggest additional vitamin K (1 to 2 mg) orally (Grade 2C).

>>>For patients with INRs > or = 9.0 and no significant bleeding, we recommend holding warfarin therapy and administering a higher dose of vitamin K (2.5 to 5 mg) orally, with the expectation that the INR will be reduced substantially in 24 to 48 h (Grade 1B). Clinicians should monitor the INR more frequently, administer additional vitamin K if necessary, and resume therapy at an appropriately adjusted dose when the INR reaches the therapeutic range.

>>>In patients with serious bleeding and elevated INR, regardless of the magnitude of the elevation, we recommend holding warfarin therapy and giving vitamin K (10 mg) by slow IV infusion supplemented with fresh frozen plasma, prothrombin complex concentrate (PCC), or recombinant factor VIIa, depending on the urgency of the situation. We recommend repeating vitamin K administration every 12 h for persistent INR elevation (all Grade 1C).

>>>In patients with life-threatening bleeding (eg, intracranial hemorrhage) and elevated INR, regardless of the magnitude of the elevation, we recommend holding warfarin therapy and administering fresh frozen plasma, PCC, or recombinant factor VIIa supplemented with vitamin K, 10 mg by slow IV infusion, repeated, if necessary, depending on the INR (Grade 1C).

>>>In patients with mild to moderately elevated INRs without major bleeding, we recommend that when vitamin K is to be given, it be administered orally rather than subcutaneously (Grade 1A).

Source:
Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:160S–198S.

Stability / Miscellaneous

ADVERSE REACTIONS-------------------------------------
Deaths have occurred after intravenous and intramuscular administration.

Transient “flushing sensations” and “peculiar” sensations of taste have been observed, as well as rare instances of dizziness, rapid and weak pulse, profuse sweating, brief hypotension, dyspnea, and cyanosis.
Pain, swelling, and tenderness at the injection site may occur.

The possibility of allergic sensitivity including an anaphylactoid reaction, should be kept in mind.

Infrequently, usually after repeated injection, erythematous, indurated, pruritic plaques have occurred; rarely, these have progressed to scleroderma-like lesions that have persisted for long periods. In other cases, these lesions have resembled erythema perstans.

Hyperbilirubinemia has been observed in the newborn following administration of phytonadione. This has occurred rarely and primarily with doses above those recommended.

DOSAGE AND ADMINISTRATION--------------------------------
Whenever possible, Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) should be given by the subcutaneous route. When intravenous administration is considered unavoidable, the drug should be injected very slowly, not exceeding 1 mg per minute.

Protect 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.

Directions for Dilution
Vitamin K1 Injection may be diluted with 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or 5% Dextrose and Sodium Chloride Injection. Benzyl alcohol as a preservative has been associated with toxicity in newborns. Therefore,all of the above diluents should be preservative-free. Other diluents should not be used. When dilutions are indicated, administration should be started immediately after mixture with the diluent, and unused portions of the dilution should be discarded, as well as unused contents of the ampul.

Prophylaxis of Hemorrhagic Disease of the Newborn
The American Academy of Pediatrics recommends that vitamin K1 be given to the newborn. A single intramuscular dose of Vitamin K1 Injection 0.5 to 1 mg within one hour of birth is recommended.

Treatment of Hemorrhagic Disease of the Newborn
Empiric administration of vitamin K1 should not replace proper laboratory evaluation of the coagulation mechanism. A prompt response (shortening of the prothrombin time in 2 to 4 hours) following administration of vitamin K1 is usually diagnostic of hemorrhagic disease of the newborn, and failure to respond indicates another diagnosis or coagulation disorder.
Vitamin K1 Injection 1 mg should be given either subcutaneously or intramuscularly. Higher doses may be necessary if the mother has been receiving oral anticoagulants.
Whole blood or component therapy may be indicated if bleeding is excessive. This therapy, however, does not correct the underlying disorder and Vitamin K1 Injection should be given concurrently.

Anticoagulant-Induced Prothrombin Deficiency in Adults
To correct excessively prolonged prothrombin time caused by oral anticoagulant therapy—2.5 to 10 mg or up to 25 mg initially is recommended. In rare instances 50 mg may be required. Frequency and amount of subsequent doses should be determined by prothrombin time response or clinical condition. If in 6 to 8 hours after parenteral administration the prothrombin time has not been shortened satisfactorily, the dose should be repeated.

HOW SUPPLIED

Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) is supplied in a package of 25 as follows:
Amount of Vitamin K1

Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

Protect from light. Keep ampuls in tray until time of use.

Source: [package insert]