Phytonadione (injection)

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# Black Box Warning

# Overview
Phytonadione (injection) is a vitamin that is FDA approved for the treatment of 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. It's also been used as a prophylaxis of hemorrhagic disease of the newborn. There is a Black Box Warning for this drug as shown here.  Common adverse reactions include skin reaction.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)

### Indications
- anticoagulant-induced prothrombin deficiency 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.

### Dosage

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Phytonadione (injection) in adult patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Phytonadione (injection) in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)

### Indications
- prophylaxis and therapy of hemorrhagic disease of the newborn.

### Dosage

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Phytonadione (injection) in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Phytonadione (injection) in pediatric patients.

# Contraindications
Hypersensitivity to any component of this medication.

# Warnings
Benzyl alcohol as a preservative in Bacteriostatic Sodium Chloride Injection has been associated with toxicity in newborns. Data are unavailable on the toxicity of other preservatives in this age group. There is no evidence to suggest that the small amount of benzyl alcohol contained in Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP), when used as recommended, is associated with toxicity.
An immediate coagulant effect should not be expected after administration of phytonadione. It takes a minimum of 1 to 2 hours for measurable improvement in the prothrombin time. Whole blood or component therapy may also be necessary if bleeding is severe.
Phytonadione will not counteract the anticoagulant action of heparin.
When vitamin K1 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 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.
Repeated large doses of vitamin K are not warranted in liver disease if the response to initial use of the vitamin is unsatisfactory. Failure to respond to vitamin K may indicate that the condition being treated is inherently unresponsive to vitamin K.
Benzyl alcohol has been reported to be associated with a fatal Gasping Syndrome in premature infants.
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 required 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.

# Adverse Reactions

## Clinical Trials Experience
- Deaths have occurred after intravenous and intramuscular 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.
- 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.

## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Phytonadione (injection) in the drug label.

# 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.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA): C
Animal reproduction studies have not been conducted with Vitamin K1 Injection. It is also not known whether Vitamin K1 Injection can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Vitamin K1 Injection should be given to a pregnant woman only if clearly needed.
Pregnancy Category (AUS): 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Phytonadione (injection) in women who are pregnant.

### Labor and Delivery
There is no FDA guidance on use of Phytonadione (injection) during labor and delivery.

### Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Vitamin K1 Injection is administered to a nursing woman.

### Pediatric Use
Hemolysis, jaundice, and hyperbilirubinemia in neonates, particularly those that are premature, may be related to the dose of Vitamin K1 Injection. Therefore, the recommended dose should not be exceeded.

### Geriatic Use
There is no FDA guidance on the use of Phytonadione (injection) with respect to geriatric patients.

### Gender
There is no FDA guidance on the use of Phytonadione (injection) with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Phytonadione (injection) with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Phytonadione (injection) in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Phytonadione (injection) in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Phytonadione (injection) in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Phytonadione (injection) in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- intramuscular
- Intravenous

### Monitoring
Prothrombin time should be checked regularly as clinical conditions indicate.

# IV Compatibility
There is limited information regarding the compatibility of Phytonadione (injection) and IV administrations.

# Overdosage
The intravenous LD50 of Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) in the mouse is 41.5 and 52 mL/kg for the 0.2% and 1% concentrations, respectively.

# Pharmacology

## Mechanism of Action
Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) aqueous dispersion of vitamin K1 for parenteral injection, possesses the same type and degree of activity as does naturally-occurring vitamin K, which is necessary for the production via the liver of active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX), and Stuart factor (factor X). The prothrombin test is sensitive to the levels of three of these four factorsII, VII, and X. Vitamin K is an essential cofactor for a microsomal enzyme that catalyzes the post-translational carboxylation of multiple, specific, peptide-bound glutamic acid residues in inactive hepatic precursors of factors II, VII, IX, and X. The resulting gamma-carboxy-glutamic acid residues convert the precursors into active coagulation factors that are subsequently secreted by liver cells into the blood.

## Structure
Phytonadione is a vitamin, which is a clear, yellow to amber, viscous, odorless or nearly odorless liquid. 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 C31H46O2 and its structural formula is:
Vitamin K1 Injection (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 2 or 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.

## Pharmacodynamics
In normal animals and humans, phytonadione is virtually devoid of pharmacodynamic activity. However, in animals and humans deficient in vitamin K, the pharmacological action of vitamin K is related to its normal physiological function, that is, to promote the hepatic biosynthesis of vitamin K dependent clotting factors.
The action of the aqueous dispersion, when administered intravenously, is generally detectable within an hour or two and hemorrhage is usually controlled within 3 to 6 hours. A normal prothrombin level may often be obtained in 12 to 14 hours.
In the prophylaxis and treatment of hemorrhagic disease of the newborn, phytonadione has demonstrated a greater margin of safety than that of the water-soluble vitamin K analogues.

## Pharmacokinetics
Phytonadione is readily absorbed following intramuscular administration. After absorption, phytonadione is initially concentrated in the liver, but the concentration declines rapidly. Very little vitamin K accumulates in tissues. Little is known about the metabolic fate of vitamin K. Almost no free unmetabolized vitamin K appears in bile or urine.

## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Phytonadione (injection) in the drug label.

# Clinical Studies
There is limited information regarding Clinical Studies of Phytonadione (injection) in the drug label.

# How Supplied
Vitamin K1 Injection (Phytonadione Injectable Emulsion, USP) is supplied in a package of 25 as follows:

## Storage
Store at 20 to 25C (68 to 77F). 
Protect from light. Keep ampuls in tray until time of use.

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Phytonadione (injection) in the drug label.

# Precautions with Alcohol
- Alcohol-Phytonadione (injection) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
- VITAMIN K1

# Look-Alike Drug Names
- Mephyton  methadone

# Drug Shortage Status

# Price