Phytonadione phytonadione - Phytonadione injection, Emulsion prescribing information
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.
INDICATIONS AND USAGE
Phytonadione injectable emulsion, USP is indicated in 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.
Phytonadione injectable emulsion is indicated in
anticoagulant-induced prothrombin deficiency caused by coumarin or indanedione derivatives;
prophylaxis and therapy of hemorrhagic disease of the newborn;
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 phytonadione injectable emulsion metabolism, e.g., salicylates.
DOSAGE AND ADMINISTRATION
Whenever possible, phytonadione injectable emulsion, should be given by the subcutaneous route. (See Box Warning .) 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
Phytonadione injectable emulsion 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 (see WARNINGS ).
Other diluents should not be used . When dilutions are indicated, administration should be startedimmediately after mixture with the diluent, and unused portions of the dilution should be discarded, as well as unused contents of the ampule.
Prophylaxis of Hemorrhagic Diseas e of the Newborn
The American Academy of Pediatrics recommends that phytonadione be given to the newborn. A single intramuscular dose of phytonadione injectable emulsion 0.5 to 1 mg within one hour of birth is recommended.
Treatment of Hemorrhagic Diseas e of the Newborn
Empiric administration of phytonadione 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 phytonadione is usually diagnostic of hemorrhagic disease of the newborn, and failure to respond indicates another diagnosis or coagulation disorder.
Phytonadione injectable emulsion 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 phytonadione injectable emulsion 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 (see WARNINGS). If in 6 to 8 hours after parenteral administration the prothrombin time has not been shortened satisfactorily, the dose should be repeated.
Phytonadione Injectable Emulsion, USP Summary of Dosage Guidelines (See circular text for details)
| Newborns | Dosage |
| Hemorrhagic Disease of the Newborn Prophylaxis | 0.5 to 1 mg IM within 1 hour of birth |
| Treatment | 1 mg SC or It (Higher doses may be necessary if the mother has been receiving oral anticoagulants) |
| Adults | Initial Dosage |
| Anticoagulant-Induced Prothrombin Deficiency(caused by coumarin or indanedione derivatives) | 2.5 mg to 10 mg or up to 25 mg (rarely 50 mg) |
| Hypoprothrombinemia Due to other causes(Antibiotics; Salicylates or other drugs; Factors limiting absorption or synthesis) | 2.5 mg to 25 mg ormore (rarely up to 50 mg) |
In the event of shock or excessive blood loss, the use of whole blood or component therapy is indicated.
Hypoprothrombinemia Due to Other Causes in Adults
A dosage of 2.5 to 25 mg or more (rarely up to 50 mg) is recommended, the amount and route of administration depending upon the severity of the condition and response obtained.
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 injectable emulsion. The severity of the coagulation disorder should determine whether the immediate administration of phytonadione injectable emulsion is required in addition to discontinuation or reduction of interfering drugs.
CONTRAINDICATIONS
Hypersensitivity to any component of this medication.
ADVERSE REACTIONS
Deaths have occurred after intravenous and intramuscular administration. (See Box Warning .) 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. (See PRECAUTIONS, Pediatric Use .)
Drug Interactions
Temporary resistance to prothrombin-depressing anticoagulants may result, especially when larger doses of phytonadione are used. If relatively large doses have been employed, it may be necessary when reinstituting anticoagulant therapy to use somewhat larger doses of the prothrombin-depressing anticoagulant, or to use one which acts on a different principle, such as heparin sodium.
DESCRIPTION
Phytonadione is a vitamin, which is a clear, yellow to amber, viscous, odorless or nearly odorlessliquid.
It is insoluble in water, soluble in chloroform and slightly soluble in ethanol. It has a molecular weight of 450.70.Phytonadione is 2-methyl-3-phytyl-1, 4-naphthoquinone. Its empirical formula is C 31 H 46 O 2 and its structural formula is:
Phytonadione injectable emulsion, USP is a yellow, sterile, nonpyrogenic aqueous dispersion available for injection by the intravenous, intramuscular and subcutaneous routes.
Each milliliter contains phytonadione 10 mg, polyoxyethylated fatty acid derivative 70 mg, dextrose, hydrous 37.5 mg in water for injection; benzyl alcohol 9 mg added as preservative. May contain hydrochloric acid for pH adjustment. pH is 6.3 (5.0 to 7.0). Phytonadione is oxygen sensitive.
CLINICAL PHARMACOLOGY
Phytonadione injectable emulsion, is indicated in 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.
Phytonadione injectable emulsion is indicated in:
• anticoagulant-induced prothrombin deficiency caused by coumarin or indanedione derivatives;
•prophylaxis and therapy of hemorrhagic disease of the newborn;
• 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 phytonadione metabolism, e.g., salicylates.
HOW SUPPLIED
Phytonadione injectable emulsion, USP is supplied as follows:
For Carton:
| Package Description | NDC |
| 25 x 1 mL Ampules | 43598-405-16 |
For Ampule:
| Package Description | Amount of Phytonadione Injectable Emulsion In Container | Volume | Concentration | NDC |
| 1 mL Ampule | 10 mg | 1 mL | 10 mg/mL | 43598-405-11 |
Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]
Protect from light. Keep ampules in carton until time of use.
Rx Only
Distributor: Dr. Reddy's Laboratories Inc. ,
Princeton, NJ 08540
Made in India
Issued: 0519
To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy's Laboratories Inc., at 1- 888-375-3784, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
