DrugindexOnline^{2nd edition}

( K ₁ ; Phylloquinone ; Methylphytyl Naphthoquinone ) Pronouncation: (fye-toe-nuh-DIE-ohn)
Class: Blood modifier, Vitamin K

Trade Names:
Mephyton
- Tablets 5 mg

Trade Names:
Phytonadione
- Injection 2 mg/mL
- Injection 10 mg/mL

Mechanism of Action

Pharmacology

Promotes hepatic synthesis of active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX) and Stuart factor (factor X).

Pharmacokinetics

Absorption

GI tract via intestinal lymphatics in the presence of bile (oral); readily absorbed (SC).

Distribution

Concentrated in the liver initially, then concentration declines rapidly.

Metabolism

Rapidly metabolized in the liver; little tissue accumulation.

Elimination

Urine and bile.

Onset

6 to 10 hr (oral) and 1 to 2 hr (parenteral); controls hemorrhage in approximately 3 to 6 hr.

Indications and Usage

Management of coagulation disorders due to faulty formation of factors II, VII, IX and X when due to vitamin K deficiency or interference with vitamin K activity.

Oral/Parenteral

Treatment of anticoagulant-induced prothrombin deficiency; treatment of hypoprothrombinemia secondary to salicylates or antibacterial therapy or secondary to obstructive jaundice and biliary fistulas, provided bile salts are also given.

Parenteral

Treatment of hypoprothrombinemia secondary to conditions limiting absorption or synthesis of vitamin K prophylaxis and therapy of hemorrhagic disease of the newborn.

Contraindications

Standard considerations.

Dosage and Administration

Adults and Children

PO / SC / IM 2.5 to 10 mg (in adults, up to 25 mg for serious bleeding; rarely, 50 mg), may repeat oral dose based on response in 6 to 8 hr (parenteral) or 12 to 48 hr (oral); avoid oral route when disorder would prevent adequate absorption.

Hemorrhagic Disease (Prophylaxis)
Newborns

IM Single dose 0.5 to 1 mg within 1 hr of birth.

Infants

PO / SC / IM 2 mg.

Hemorrhagic Disease (Treatment)
Newborns

SC / IM 1 mg accompanied by laboratory evaluation.

General Advice

• Give SC or IM when possible. For adults and older children, inject IM in upper outer quadrant of buttocks. In infants and young children, anterolateral aspect of thigh or deltoid region is preferred.
• Avoid IV route unless risk outweighs benefit. If IV administration is unavoidable, inject very slowly, not exceeding 1 mg/min.

Storage/Stability

Protect from light at all times.

Drug Interactions

Oral anticoagulants

Effects are antagonized by vitamin K, particularly in patients with advanced liver disease.

Laboratory Test Interactions

Paradoxical prolongation of prothrombin time (PT) after max doses of vitamin K.

Adverse Reactions

Cardiovascular

Hypotension; cyanosis.

CNS

Headache; dizziness.

Dermatologic

Pruritic erythematous plaques at IM injection site; rash; urticaria.

Hepatic

Hyperbilirubinemia, including kernicterus, in newborns.

Miscellaneous

Anaphylactoid reactions; pain, swelling and tenderness at injection site; death after IV injection.

Precautions

Warnings Phytonadione injection Severe reactions, including death, have occurred during and immediately after IV injection. Severe reactions have resembled hypersensitivity or anaphylaxis, including shock and cardiac and/or respiratory arrest. Events have occurred even when appropriate dilution was used to avoid rapid infusion. Some patients have exhibited symptoms on first administration of the drug. Thus, restrict IV use for situations where other routes are not feasible and benefit/risk ratio is assessed.

Pregnancy

Category C .

Lactation

Vitamin K excreted in breast milk.

Hypersensitivity

Rash and urticaria; anaphylactoid reactions.

Hepatic Function

Giving vitamin K to correct hypoprothrombinemia associated with severe hepatitis or cirrhosis may further depress prothrombin concentration.

Anticoagulation

Patient may be refractory to oral anticoagulants, particularly large doses.

Bleeding

Giving vitamin K has no immediate coagulant effect. Management of bleeding involves standard measures (eg, transfusions).

Overdosage

Symptoms

Parenteral administration: Hypotension, asystole, chest pain, dyspnea, nausea, rash, pruritus.

Patient Information

• Explain that patient may experience temporary “flushing sensations” and “peculiar” sensations of taste. Rarely dizziness, rapid weak pulse, profuse sweating, or difficulty breathing may occur. Another rare occurrence is pain, swelling, or tenderness at injection site.
• Remind patients on anticoagulant and phytonadione therapy of importance of regular lab work to check PT. Anticoagulant effects are antagonized by vitamin K so temporary resistance to oral anticoagulants may result, especially when larger doses are used.
• Instruct patient to report any symptoms of bleeding.