PHYTONADIONE
Brand names: PHYTONADIONE, Phytonadione, phytonadione, PHYTONADIONE PHYTONADIONE, Vitamin K1
Boxed warning
WARNING — INTRAVENOUS AND INTRAMUSCULAR USE Severe reactions, including fatalities, have occurred during and immediately after INTRAVENOUS injection of phytonadione, even when precautions have been taken to dilute the phytonadione and to avoid rapid infusion. Severe reactions, including fatalities, have also been reported following INTRAMUSCULAR administration. Typically these severe reactions have resembled hypersensitivity or anaphylaxis, including shock and cardiac and/or respiratory arrest. Some patients have exhibited these severe reactions on receiving phytonadione for the first time. Therefore the INTRAVENOUS and INTRAMUSCULAR routes should be restricted to those situations where the subcutaneous route is not feasible and the serious risk involved is considered justified.
Warnings
WARNING: HYPERSENSITIVITY REACTIONS WITH INTRAVENOUS AND INTRAMUSCULAR USE Fatal hypersensitivity reactions, including anaphylaxis, have occurred during and immediately after intravenous and intramuscular injection of phytonadione injectable emulsion. Reactions have occurred despite dilution to avoid rapid intravenous infusion and upon first dose. Avoid the intravenous and intramuscular routes of administration unless the subcutaneous route is not feasible and the serious risk is justified [see Warnings and Precautions (5.1) ] . WARNING: HYPERSENSITIVITY REACTIONS WITH INTRAVENOUS AND INTRAMUSCULAR USE See full prescribing information for complete boxed warning. Fatal hypersensitivity reactions, including anaphylaxis, have occurred during and immediately after INTRAVENOUS and INTRAMUSCULAR injection of phytonadione injectable emulsion. Reactions have occurred despite dilution to avoid rapid infusion and upon first and subsequent doses. Avoid the intravenous and intramuscular routes of administration unless the subcutaneous route is not feasible and the serious risk is justified. ( 5.1 )
5 WARNINGS AND PRECAUTIONS Cutaneous Reactions: May occur with parenteral use. Discontinue drug and manage medically. ( 5.3 ) 5.1 Hypersensitivity Reactions Fatal and severe hypersensitivity reactions, including anaphylaxis, have occurred with intravenous or intramuscular administration of phytonadione injectable emulsion. Reactions have occurred despite dilution to avoid rapid intravenous infusion and upon first dose. These reactions have included shock, cardiorespiratory arrest, flushing, diaphoresis, chest pain, tachycardia, cyanosis, weakness, and dyspnea. Administer phytonadione injectable emulsion subcutaneously whenever feasible. Avoid the intravenous and intramuscular routes of administration unless the subcutaneous route is not feasible and the serious risk is justified [see Dosage and Administration (2.1) ] . 5.3 Cutaneous Reactions Parenteral administration of vitamin K replacements (including phytonadione injectable emulsion) may cause cutaneous reactions. Reactions have included eczematous reactions, scleroderma-like patches, urticaria, and delayed-type hypersensitivity reactions. Time of onset ranged from 1 day to a year after parenteral administration. Discontinue phytonadione injectable emulsion for skin reactions and institute medical management. 5.4 Aluminum Toxicity WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
Contraindications
4 CONTRAINDICATIONS Phytonadione tablets are contraindicated in patients with a history of a hypersensitivity reaction to phytonadione or inactive ingredients [see Description ( 11 )] . Hypersensitivity to any component of this medication. ( 4 )
Overdose
OVERDOSAGE The intravenous LD 50 of phytonadione injectable emulsion in the mouse is 41.5 and 52 mL/kg for the 0.2% and 1% concentrations, respectively.
Drug interactions
7 DRUG INTERACTIONS Anticoagulants Phytonadione may induce temporary resistance to prothrombin-depressing anticoagulants, especially when larger doses of phytonadione are used. Should this occur, higher doses of anticoagulant therapy may be needed when resuming anticoagulant therapy, or a change in therapy to a different class of anticoagulant may be necessary (i.e., heparin sodium). Phytonadione does not affect the anticoagulant action of heparin. Anticoagulants: May induce temporary resistance to prothrombin-depressing anticoagulants. ( 7 )
Uses
1 INDICATIONS AND USAGE Phytonadione injectable emulsion is a vitamin K replacement indicated for the treatment of the following coagulation disorders which are due to faulty formation of factors II, VII, IX and X when caused by vitamin K deficiency or interference with vitamin K activity. Anticoagulant-induced hypoprothrombinemia deficiency caused by coumarin or indanedione derivatives. ( 1.1 ) Hypoprothrombinemia due to antibacterial therapy. ( 1.1 ) Hypoprothrombinemia secondary to factors limiting absorption or synthesis of vitamin K, e.g., obstructive jaundice, biliary fistula, sprue, ulcerative colitis, celiac disease, intestinal resection, cystic fibrosis of the pancreas, and regional enteritis. ( 1.1 ) Other drug-induced hypoprothrombinemia where it is definitely shown that the result is due to interference with vitamin K metabolism, e.g., salicylates. ( 1.1 ) Phytonadione injectable emulsion is indicated for prophylaxis and treatment of vitamin K deficiency bleeding in neonates. ( 1.2 ) 1.1 Treatment of Hypoprothrombinemia Due to Vitamin K Deficiency or Interference Phytonadione injectable emulsion is indicated for the treatment of the following coagulation disorders which are due to faulty formation of factors II, VII, IX and X when caused by vitamin K deficiency or interference with vitamin K activity: anticoagulant-induced hypoprothrombinemia caused by coumarin or indanedione derivatives; hypoprothrombinemia due to antibacterial therapy; hypoprothrombinemia secondary to factors limiting absorption or synthesis of vitamin K, e.g., obstructive jaundice, biliary fistula, 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. 1.2 Prophylaxis and Treatment of Vitamin K Deficiency Bleeding in Neonates Phytonadione injectable emulsion is indicated for prophylaxis and treatment of vitamin K deficiency bleeding in neonates.
Dosage forms & strengths
2 DOSAGE AND ADMINISTRATION Anticoagulant-Induced Prothrombin Deficiency: 2.5 mg to 10 mg or up to 25 mg ( 2.2 ) Hypoprothrombinemia Due to Other Causes: 2.5 mg to 25 mg or more ( 2.2 ) Must be given with bile salts when endogenous supply of bile to gastrointestinal track is deficient. ( 2.1 ) 2.1 Dosing Considerations Avoid the oral route when the clinical disorder would prevent proper absorption. Bile salts must be given with the tablets when the endogenous supply of bile to the gastrointestinal tract is deficient. The coagulant effects of phytonadione tablets are not immediate; improvement of international normalized ratio (INR) may take 1 to 8 hours. Interim use of whole blood or component therapy may also be necessary if bleeding is severe. Phytonadione tablets will not counteract the anticoagulant action of heparin. When phytonadione tablets are 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. Phytonadione is not a clotting agent, but overzealous therapy with vitamin K1 may restore conditions which originally permitted thromboembolic phenomena. Dosage should be kept as low as possible, and prothrombin time should be checked regularly as clinical conditions indicate. 2.2 Recommended Dosage Anticoagulant-Induced Prothrombin Deficiency in Adults The recommended dose to correct excessively prolonged prothrombin times caused by oral anticoagulant therapy is, 2.5 to 10 mg or up to 25 mg initially. In some instances 50 mg may be required. Frequency and amount of subsequent doses should be determined by prothrombin time response or clinical condition. If, in 12 to 48 hours after oral administration, the prothrombin time has not been shortened satisfactorily, repeat the dose. Repeated large doses of phytonadione tablets are not warranted in liver disease if the response to initial use of the vitamin is unsatisfactory. Failure to respond to phytonadione tablets may indicate a congenital coagulation defect or that the condition being treated is unresponsive to vitamin K. Hypoprothrombinemia Due to Other Causes in Adults If possible, discontinuation or reduction of the dosage of drugs interfering with coagulation mechanisms (such as salicylates, antibiotics) is suggested as an alternative to administering concurrent phytonadione tablets. The severity of the coagulation disorder should determine whether the immediate administration of phytonadione tablets is required in addition to discontinuation or reduction of interfering drugs. The recommended dose is 2.5 mg to 25 mg or more (sometimes up to 50 mg). Evaluate INR after 6 to 8 hours, and repeat dose if INR remains prolonged. Modify subsequent dosage (amount and frequency) based upon the INR or clinical condition.
All identified pills
Side effects
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Cutaneous Reactions [see Warnings and Precautions (5.3) ] Most common adverse reactions are cyanosis, diaphoresis, dizziness, dysgeusia, dyspnea, flushing, hypotension and tachycardia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals LLC at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. 6.2 Post-marketing Experience The following adverse reactions have been identified during post-approval use of phytonadione injectable emulsion. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac Disorders: Tachycardia, hypotension. General Disorders and Administration Site Conditions: Generalized flushing; pain, swelling, and tenderness at injection site. Hepatobiliary Disorders: Hyperbilirubinemia. Immune System Disorders: Fatal hypersensitivity reactions, anaphylactic reactions. Neurologic: Dysgeusia, dizziness. Pulmonary: Dyspnea. Skin and Subcutaneous Tissue Disorders: Erythema, pruritic plaques, scleroderma-like lesions, erythema perstans. Vascular: Cyanosis.