Phytonadione

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Phytonadione is a man-made form of vitamin K, which occurs naturally in the body.

Phytonadione is used to treat vitamin K deficiency and to treat certain bleeding or blood clotting problems.

Phytonadione may also be used for purposes not listed in this medication guide.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

General

• Restrict IV or IM administration to situations when sub-Q is not possible.a

• Monitor prothrombin time regularly as dictated by clinical condition.b

• If possible, discontinue or reduce dosage of drugs interfering with the coagulation mechanism as an alternative or adjunct to phytonadione therapy.c

• Diagnosis of vitamin K deficiency may be based on tests for vitamin K-dependent clotting factors (e.g., prothrombin time, which is sensitive to the levels of factors II, VII, and X) or on a therapeutic trial of phytonadione.c

Administration

Administer orally or parenterally.a b

Parental therapy: Sub-Q preferred because of hypersensitivity risk with IV or IM administration.a (See Boxed Warning.)

Route of administration depends on the severity of the prothrombin deficiency and the risks associated with administration by each route.c

Oral Administration

Avoid oral route when the clinical disorder would prevent proper absorption.b

Patients with decreased bile secretion: Give bile salts (e.g., ox bile extract 300 mg or dehydrocholic acid 500 mg) with each oral dose of phytonadione to ensure absorption.b c

The parenteral preparation has also been administered orally† to neonates.34 35 37 102 103 104 105 136

IV, IM, or Sub-Q Administration

Because of the possibility of severe hypersensitivity reactions, IV or IM administration is indicated only when the serious risk involved is considered justified and other routes of administration are not feasible.b (See Boxed Warning.)

Parenteral administration is indicated in patients unable to retain or absorb the drug from the GI tract.c

Sub-Q or IM administration may be contraindicated in hypoprothrombinemia because of the possibility of inducing hemorrhage or hematoma at the site of injection.c

Dilute for infusion with preservative-free 5% dextrose, 0.9% sodium chloride, or 5% dextrose in 0.9% sodium chloride injection; other diluents should not be used.c

Administer IV immediately after dilution, and any unused portion of the dilution and the unused contents of the ampul should be discarded.c The infusion container must be protected from light at all times.c (See Storage under Stability.)

Inject IV very slowly, at a rate ≤1 mg/minute.b (See Boxed Warning.)

Dosage

Dose, frequency of administration, and duration of treatment depend on the severity of the prothrombin deficiency and the response of the patient.c

Pediatric Patients

AAP recommends a single IM dose of 0.5–1 mg within 1 hour of delivery.34 113 135 136 c f

Alternatively, 1–2 mg orally† (can use injection formulation) immediately after delivery.135 136 137 Several oral doses, administered over a period of up to 3 months, may be required (e.g., at 1–2 weeks and 4 weeks of age in breast-fed infants, repeatedly if diarrhea occurs in breast-fed infants).135 136 137 f

Empiric administration should not replace proper laboratory evaluation of the coagulation mechanism.b

A prompt response (shortening of the prothrombin time in 2–4 hours) following phytonadione usually is diagnostic of hemorrhagic disease of the newborn, and failure to respond indicates another diagnosis or coagulation disorder.b

1 mg sub-Q or IM.b Higher doses may be necessary if the mother has been receiving oral anticoagulants.b

2 mcg daily.121

2.5 mcg daily.121

30 mcg daily.121

55 mcg daily.121

60 mcg daily.121

75 mcg daily.121

Adults

Usual initial dosage: 2.5–10 mg.a Initial doses up to 25 mg have been used.a

Subsequent frequency and dosage should be determined by prothrombin time response and/or clinical condition.a

Dose may be repeated in 12–48 hours.a

Rarely, larger doses (e.g., 50 mg) may be required; however, administer lowest effective dosage so that refractoriness to further anticoagulant therapy is minimized and prothrombin time is not decreased below the effective anticoagulant level.a c

Usual initial dosage: 2.5–10 mg.b Initial doses up to 25 mg have been used.b

Subsequent frequency and dosage should be determined by prothrombin time response and/or clinical condition.b

Dose may be repeated in 6–8 hours.b

Rarely, larger doses (e.g., 50 mg) may be required; however, administer lowest effective dosage so that refractoriness to further anticoagulant therapy is minimized and prothrombin time is not decreased below the effective anticoagulant level.b c

Usual initial dosage: 2.5–25 mg, depending on deficiency, severity, and response.a Rarely, larger doses (e.g., 50 mg) may be required.a

Determine subsequent frequency and dosage by prothrombin time response and/or clinical condition in addition to reduction or discontinuance of drug (if drug therapy causing hypoprothrombinemia).a

Usual initial dosage: 2.5–25 mg, depending on deficiency severity and response.a Rarely, larger doses (e.g., 50 mg) may be required.a

Determine subsequent frequency and dosage by prothrombin time response and/or clinical condition in addition to reduction or discontinuance of interfering drug (if drug therapy causing hypoprothrombinemia).a

120 mcg daily.121

90 mcg daily.121

Limited data suggest that the vitamin K status in pregnant women does not differ from that in nonpregnant women.121 Therefore, NAS states that the AI of vitamin K does not need to be increased during pregnancy (i.e., pregnant women can receive the usual AI appropriate for their age).121

Available evidence indicates that the vitamin K status of lactating women is comparable to that of nonlactating women.121 Vitamin K is not distributed in clinically important amounts into milk, and the AI for lactating women does not differ from that for nonlactating women.121

Special Populations

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.a

Severe hypersensitivity reactions, including anaphylactoid reactions and deaths have been reported following parenteral administration. The majority of these reported events occurred following intravenous administration (see Box Warning.)

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

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. (See PRECAUTIONS, Pediatric Use.)

Hypoprothrombinemia due to long-acting anticoagulant rodenticides (LAARs)

Data from a few case reports suggest that phytonadione may be beneficial in the treatment of hypoprothrombinemia caused by long-acting anticoagulant rodenticides (brodifacoum) [Bruno 2000], [Gunja 2011], [Olmos 2007]. Data from a limited number of patients (case series) also suggest that phytonadione may be beneficial in this setting [Chua 1998]. Additional data may be necessary to further define the role of phytonadione in the treatment of this condition.

Intracranial hemorrhage associated with vitamin K antagonist anticoagulants (eg, warfarin)

Based on the Neurocritical Care Society and the Society of Critical Care Medicine guideline for reversal of antithrombotics in intracranial hemorrhage, phytonadione, with 4-factor prothrombin complex concentrate (PCC), is recommended as soon as possible for vitamin K antagonist-associated intracranial hemorrhage and INR ≥1.4. Three-factor PCC may be given with phytonadione but 4-factor PCC is preferred [NCS/SCCM [Frontera 2016]].

Refer to adult dosing.

No dosage adjustment provided in manufacturer’s labeling.

A 1 mg/mL oral suspension may be made with tablets. Crush six 5 mg tablets in a mortar and reduce to a fine powder. Add 5 mL each of water and methylcellulose 1% and mix to a uniform paste. Mix while adding sorbitol in incremental proportions to almost 30 mL; transfer to a calibrated bottle, rinse mortar with sorbitol, and add quantity of sorbitol sufficient to make 30 mL. Label "shake well" and "refrigerate". Stable for 3 days.

Note: The parenteral formulation may also be used for small oral doses (eg, 1 mg) or situations in which tablets cannot be swallowed (Crowther, 2000; O’Connor, 1986); may administer undiluted or diluted in a beverage (eg, orange juice) (Vanier 2006).

IV administration: Infuse slowly; rate of infusion should not exceed 1 mg/minute. Alternatively, dilute dose in a minimum of 50 mL of compatible solution and administer using an infusion pump over at least 20 minutes (Ageno 2012). The injectable route should be used only if the oral route is not feasible or there is a greater urgency to reverse anticoagulation.

Oral: The parenteral formulation may also be used for small oral doses (eg, 1 mg) or situations in which tablets cannot be swallowed (Crowther 2000; Crowther 2002; O’Connor 1986); may administer undiluted or diluted in a beverage (eg, orange juice) (Vanier 2006).

Severe reactions, including fatalities, have occurred during and immediately after intravenous (IV) injection of phytonadione, even when precautions have been taken to dilute the phytonadione and to avoid rapid infusion. Severe reactions, including fatalities, also have been reported following intramuscular (IM) administration. Typically, these severe reactions have resembled hypersensitivity or anaphylaxis, including shock and cardiac or respiratory arrest. Some patients have exhibited these severe reactions on receiving phytonadione for the first time. Therefore, restrict the IV and IM routes to those situations where the subcutaneous route is not feasible and the serious risk involved is considered justified.

PT, INR; monitor for hypersensitivity reactions if administering IV.

Initial dose: 2.5 to 25 mg or more, orally or subcutaneously (SC)
Maximum dose: Rarely up to 50 mg

Comments:
-Use concurrent bile salts if giving orally if obstructive jaundice or biliary fistula are present, otherwise vitamin K will not be absorbed.

Uses:
The following coagulation disorders when caused by deficiency or interference with vitamin K activity:
-Hypoprothrombinemia secondary to antibacterials or salicylates;
-Hypoprothrombinemia secondary to obstructive jaundice or biliary fistulas;
-Hypoprothrombinemia secondary to limited absorption or synthesis of vitamin K, e.g., sprue, ulcerative colitis, celiac disease, intestinal resection, cystic fibrosis of the pancreas, and regional enteritis
-Other drug-induced hypoprothrombinemia where it is definitely shown that the result is due to interference with vitamin K metabolism, e.g., salicylates