Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING Phytonadione Injectable Emulsion USP, 1 mg/0.5 mL is available as clear yellow color, solution filled in prefilled glass syringe with SRC tip cap, assembled with grey plunger stopper and natural plunger rod. It is supplied in carton containing ten plastic trays, each having one single-dose prefilled glass syringes and one, SurGuard ® 3 safety hypodermic 27 G. x 1/2” needle with the following presentations: Unit of Sale Strength Each NDC 70121-1682-7 (Carton of 10) 1 mg/0.5 mL NDC 70121-1682-1 (0.5 mL prefilled syringe) Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect phytonadione injectable emulsion from light. Store container in closed original carton until contents have been used. Syringe Assembly Directions: See User Guide USE ASEPTIC TECHNIQUE Do not remove from carton or assemble until ready to use. CAUTION: The syringe may not be compatible with Luer-activated valve (LAV) connectors that have internal pin designs, such as LAVs with CLAVE design. 1. Remove the prefilled syringe cap by unscrewing it counter-clockwise (see Figure A) . Figure A 2. Open the needle package by using both thumbs to pull apart the packaging (see Figure B) . Remove the needle from the package. Figure B 3. Attach the needle with the needle cap to the syringe by turning clockwise until it cannot twist any further (see Figure C) . Do not remove the needle cap. Figure C Pull back the needle safety shield (see Figure D) . Figure D 4. Carefully remove needle cap from the needle by pulling straight off (see Figure E) and throw it away in a sharp disposal container. Make sure the needle does not touch anything before the injection. Figure E 5. Hold the syringe at eye level with the needle pointing upwards. Check to see air bubble. Remove it by tapping the side of the syringe with your finger until it rise towards the tip (see Figure F) . Then, slowly push the plunger up until a small amount of liquid drips from the needle (see Figure G) . Figure F Figure G 6. After injection, position shield in preparation for device activation: Using a one-handed technique, push the tab forward with your finger or thumb so that the shield is less than 90 degrees from the needle (see Figure H) . NOTE: Keep your finger or thumb behind the tab at all times. Figure H 7. Activate shield: Position the shield approximately 45 degrees to flat surface. Press down with a GENTLE, QUICK, MOTION until a distinct AUDIBLE CLICK is heard (see Figure I) . Note: Audible click may not be heard on small needle sizes: visual confirmation is required. Figure I 8. VISUALLY CONFIRM that needle is fully engaged under lock (see Figure J) . Figure J 9. Following activation of the needle shield, immediately discard the unit into an approved sharps container. CAUTION: LIQUID IN GLASS. HANDLE WITH CARE. INSPECT SYRINGE FOR DAMAGE PRIOR TO ASSEMBLY. 01 02 03 04 05 06 07 08 09 10; PRINCIPAL DISPLAY PANEL NDC 70121-1682-1 Phytonadione Injectable Emulsion USP, 1 mg/0.5 mL 0.5 mL Prefilled Syringe Label Rx only Amneal Pharmaceuticals LLC NDC 70121-1682-1 Phytonadione Injectable Emulsion USP, 1 mg/0.5 mL 0.5 mL Tray Label Rx only Amneal Pharmaceuticals LLC NDC 70121-1682-7 Phytonadione Injectable Emulsion USP, 1 mg/0.5 mL 10 x 0.5 mL Carton Label Rx only Amneal Pharmaceuticals LLC 1 002 2
- 16 HOW SUPPLIED/STORAGE AND HANDLING Phytonadione Injectable Emulsion USP, 1 mg/0.5 mL is available as clear yellow color, solution filled in prefilled glass syringe with SRC tip cap, assembled with grey plunger stopper and natural plunger rod. It is supplied in carton containing ten plastic trays, each having one single-dose prefilled glass syringes and one, SurGuard ® 3 safety hypodermic 27 G. x 1/2” needle with the following presentations: Unit of Sale Strength Each NDC 70121-1682-7 (Carton of 10) 1 mg/0.5 mL NDC 70121-1682-1 (0.5 mL prefilled syringe) Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect phytonadione injectable emulsion from light. Store container in closed original carton until contents have been used. Syringe Assembly Directions: See User Guide USE ASEPTIC TECHNIQUE Do not remove from carton or assemble until ready to use. CAUTION: The syringe may not be compatible with Luer-activated valve (LAV) connectors that have internal pin designs, such as LAVs with CLAVE design. 1. Remove the prefilled syringe cap by unscrewing it counter-clockwise (see Figure A) . Figure A 2. Open the needle package by using both thumbs to pull apart the packaging (see Figure B) . Remove the needle from the package. Figure B 3. Attach the needle with the needle cap to the syringe by turning clockwise until it cannot twist any further (see Figure C) . Do not remove the needle cap. Figure C Pull back the needle safety shield (see Figure D) . Figure D 4. Carefully remove needle cap from the needle by pulling straight off (see Figure E) and throw it away in a sharp disposal container. Make sure the needle does not touch anything before the injection. Figure E 5. Hold the syringe at eye level with the needle pointing upwards. Check to see air bubble. Remove it by tapping the side of the syringe with your finger until it rise towards the tip (see Figure F) . Then, slowly push the plunger up until a small amount of liquid drips from the needle (see Figure G) . Figure F Figure G 6. After injection, position shield in preparation for device activation: Using a one-handed technique, push the tab forward with your finger or thumb so that the shield is less than 90 degrees from the needle (see Figure H) . NOTE: Keep your finger or thumb behind the tab at all times. Figure H 7. Activate shield: Position the shield approximately 45 degrees to flat surface. Press down with a GENTLE, QUICK, MOTION until a distinct AUDIBLE CLICK is heard (see Figure I) . Note: Audible click may not be heard on small needle sizes: visual confirmation is required. Figure I 8. VISUALLY CONFIRM that needle is fully engaged under lock (see Figure J) . Figure J 9. Following activation of the needle shield, immediately discard the unit into an approved sharps container. CAUTION: LIQUID IN GLASS. HANDLE WITH CARE. INSPECT SYRINGE FOR DAMAGE PRIOR TO ASSEMBLY. 01 02 03 04 05 06 07 08 09 10
- PRINCIPAL DISPLAY PANEL NDC 70121-1682-1 Phytonadione Injectable Emulsion USP, 1 mg/0.5 mL 0.5 mL Prefilled Syringe Label Rx only Amneal Pharmaceuticals LLC NDC 70121-1682-1 Phytonadione Injectable Emulsion USP, 1 mg/0.5 mL 0.5 mL Tray Label Rx only Amneal Pharmaceuticals LLC NDC 70121-1682-7 Phytonadione Injectable Emulsion USP, 1 mg/0.5 mL 10 x 0.5 mL Carton Label Rx only Amneal Pharmaceuticals LLC 1 002 2
Overview
Phytonadione, USP is a vitamin K replacement, which is a clear, yellow to amber, very viscous liquid. It is soluble in dehydrated alcohol, in benzene, in chloroform, in ether and in vegetable oils; slightly soluble in alcohol and insoluble in water. It has a molecular weight of 450.70 g/mol. Phytonadione is 2-Methyl-3-(3,7,11,15-tetramethylhexadec-2-en-1-yl)naphthalene-1,4-dione. Its molecular formula is C 31 H 46 O 2 and its molecular structure is: Phytonadione Injectable Emulsion, USP is a sterile, clear yellow color solution of vitamin K 1 , with a pH of 3.5 to 7.0, available for injection by the intravenous, intramuscular and subcutaneous routes. Phytonadione injectable emulsion, USP is available in 1 mg (1 mg/0.5 mL) single-dose prefilled glass syringe. Each 0.5 mL of Phytonadione Injectable Emulsion, USP contains: Active: Phytonadione, USP (Vitamin K1)………………1 mg Inactive: Polysorbate 80 …………………………10 mg Propylene glycol ………………………10.4 mg Sodium acetate anhydrous.…………..…0.17 mg Glacial acetic acid .………….….….......0.00002 mL Water for injection.….…………………q.s. to 0.5 mL Additional glacial acetic acid or sodium acetate anhydrous may have been added to adjust pH to meet USP limits of 3.5 to 7.0. 1
Indications & 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 & Administration
Administer phytonadione injectable emulsion by the subcutaneous route, whenever possible. ( 2.1 ) When intravenous administration is unavoidable, inject the drug very slowly, not exceeding 1 mg per minute. ( 2.1 ) 2.1 Dosing Considerations Whenever possible, administer phytonadione injectable emulsion by the subcutaneous route [see Boxed Warning ] . When intravenous administration is unavoidable, inject the drug very slowly, not exceeding 1 mg per minute [see Warnings and Precautions (5.1) ] . Monitor international normalized ratio (INR) regularly and as clinical conditions indicate. Use the lowest effective dose of phytonadione injectable emulsion. The coagulant effects of phytonadione injectable emulsion are not immediate; improvement of INR may take 1 hour to 8 hours. Interim use of whole blood or component therapy may also be necessary if bleeding is severe. When phytonadione injectable emulsion is 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 phytonadione injectable emulsion may restore conditions which originally permitted thromboembolic phenomena. Dosage should be kept as low as possible and INR should be checked regularly as clinical conditions indicate. 2.2 Recommended Dosage for Coagulation Disorders from Vitamin K Deficiency or Interference The recommended dosage of phytonadione injectable emulsion is based on whether the hypoprothrombinemia is anticoagulant-induced (e.g., due to coumarin or indanedione derivatives) or non-anticoagulant-induced (e.g., due to antibiotics; salicylates or other drugs; factors limiting absorption or synthesis) as follows: Anticoagulant-Induced Hypoprothrombinemia: Phytonadione injectable emulsion 2.5 mg to 10 mg or more subcutaneously, intramuscularly, or intravenously. Up to 25 mg to 50 mg may be administered as a single-dose. Repeated large doses of phytonadione injectable emulsion are not warranted in liver disease if the initial response is unsatisfactory. Failure to respond to phytonadione injectable emulsion may indicate that the condition being treated is inherently unresponsive to phytonadione injectable emulsion. Hypoprothrombinemia Due to Other Causes (Non-Anticoagulation-Induced Hypoprothrombinemia): Phytonadione injectable emulsion 2.5 mg to 25 mg or more intravenously, intramuscularly, or subcutaneously. Up to 50 mg may be administered as a single-dose. Evaluate INR after 6 hours to 8 hours and repeat dose if INR remains prolonged. Modify subsequent dosage (amount and frequency) based on the INR or clinical condition. 2.3 Recommended Dosage for Prophylaxis and Treatment of Vitamin K Deficiency Bleeding in Neonates Prophylaxis of Vitamin K-Deficiency Bleeding in Neonates The recommended dosage of phytonadione injectable emulsion is 0.5 mg to 1 mg within one hour of birth for a single-dose. Treatment of Vitamin K-Deficiency Bleeding in Neonates The recommended dosage of phytonadione injectable emulsion is 1 mg given either subcutaneously or intramuscularly. Consider higher doses if the mother has been receiving oral anticoagulants. A failure to respond (shortening of the INR in 2 hours to 4 hours) may indicate another diagnosis or coagulation disorder. 2.4 Directions for Dilution CAUTION: The syringe may not be compatible with Luer-activated valve (LAV) connectors that have internal pin designs, such as LAVs with CLAVE design. Dilute phytonadione injectable emulsion with 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or 5% Dextrose and Sodium Chloride Injection. When diluted, start administration of phytonadione injectable emulsion immediately after dilution. Discard unused portions of diluted solution as well as unused contents of the syringe. Protect phytonadione injectable emulsion 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.
Warnings & 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.
Boxed 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 )
Contraindications
Hypersensitivity to phytonadione or any other component of this medication [see Warnings and Precautions (5.1) ] . Hypersensitivity to any component of this medication. ( 4 )
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 and Post-Marketing 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. 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.
Drug Interactions
Anticoagulants Phytonadione injectable emulsion may induce temporary resistance to prothrombin-depressing anticoagulants, especially when larger doses of phytonadione injectable emulsion 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 injectable emulsion does not affect the anticoagulant action of heparin. Anticoagulants: May induce temporary resistance to prothrombin-depressing anticoagulants. ( 7 )
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