NDC 51662-1414 Protamine Sulfate

Protamine Sulfate

NDC Product Information

Protamine Sulfate with NDC 51662-1414 is a a human prescription drug product labeled by Hf Acquisition Co Llc, Dba Healthfirst. The generic name of Protamine Sulfate is protamine sulfate. The product's dosage form is injection, solution and is administered via intravenous form.

Labeler Name: Hf Acquisition Co Llc, Dba Healthfirst

Dosage Form: Injection, Solution - A liquid preparation containing one or more drug substances dissolved in a suitable solvent or mixture of mutually miscible solvents that is suitable for injection.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Protamine Sulfate Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • PROTAMINE SULFATE 10 mg/mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • SODIUM CHLORIDE (UNII: 451W47IQ8X)
  • SODIUM PHOSPHATE, DIBASIC (UNII: GR686LBA74)
  • SULFURIC ACID (UNII: O40UQP6WCF)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intravenous - Administration within or into a vein or veins.
  • Intravenous - Administration within or into a vein or veins.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Heparin Binding Activity - [MoA] (Mechanism of Action)
  • Heparin Reversal Agent - [EPC] (Established Pharmacologic Class)
  • Reversed Anticoagulation Activity - [PE] (Physiologic Effect)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Hf Acquisition Co Llc, Dba Healthfirst
Labeler Code: 51662
FDA Application Number: ANDA089454 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 10-13-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Protamine Sulfate Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Other

For Intravenous Use

Www.fresenius-kabi.us

45848G
Revised: December 2016

Description

Protamines are simple proteins of low molecular weight that are rich in arginine and strongly basic. They occur in the sperm of salmon and certain other species of fish.Protamine sulfate occurs as fine white or off-white amorphous or crystalline powder. It is sparingly soluble in water. The pH is between 6.0 and 7.0. The cationic hydrogenated protamine at a pH of 6.8 to 7.1 reacts with anionic heparin at a pH of 5.0 to 7.5 to form an inactive complex.Protamine Sulfate Injection, USP is a sterile, isotonic solution of protamine sulfate. It acts as a heparin antagonist. It is also a weak anticoagulant.Each mL contains: Protamine sulfate 10 mg; sodium chloride 9 mg; Water for Injection q.s. Sulfuric acid and/or dibasic sodium phosphate (heptahydrate) may have been added for pH adjustment.The preparation is preservative free.Protamine sulfate is administered intravenously.

Clinical Pharmacology

When administered alone, protamine has an anticoagulant effect. However, when it is given in the presence of heparin (which is strongly acidic), a stable salt is formed and the anticoagulant activity of both drugs is lost.Protamine sulfate has a rapid onset of action. Neutralization of heparin occurs within five minutes after intravenous administration of an appropriate dose of protamine sulfate. Although the metabolic fate of the heparin-protamine complex has not been elucidated, it has been postulated that protamine sulfate in the heparin-protamine complex may be partially metabolized or may be attacked by fibrinolysin, thus freeing heparin.

Indications & Usage

Protamine Sulfate Injection, USP is indicated in the treatment of heparin overdosage.

Contraindications

Protamine sulfate is contraindicated in patients who have shown previous intolerance to the drug.

Warnings

Hyperheparinemia or bleeding has been reported in experimental animals and in some patients 30 minutes to 18 hours after cardiac surgery (under cardiopulmonary bypass) in spite of complete neutralization of heparin by adequate doses of protamine sulfate at the end of the operation. It is important to keep the patient under close observation after cardiac surgery. Additional doses of protamine sulfate should be administered if indicated by coagulation studies, such as the heparin titration test with protamine and the determination of plasma thrombin time.Too-rapid administration of protamine sulfate can cause severe hypotensive and anaphylactoid reactions (see
DOSAGE & ADMINISTRATION and
WARNINGS). Facilities to treat shock should be available.

Precautions

GeneralBecause of the anticoagulant effect of protamine, it is unwise to give more than 50 mg over a short period unless a larger dose is clearly needed.Patients with a history of allergy to fish may develop hypersensitivity reactions to protamine, although to date no relationship has been established between allergic reactions to protamine and fish allergy.Previous exposure to protamine can induce a humoral immune response and predispose susceptible individuals to the development of untoward reactions from the subsequent use of this drug. Patients exposed to protamine through the use of protamine-containing insulin or during heparin neutralization may experience life-threatening reactions and fatal anaphylaxis upon receiving large doses of protamine intravenously. Severe reactions to intravenous protamine can occur in the absence of local or systemic allergic reactions to subcutaneous injection of protamine-containing insulin. Reports of the presence of antiprotamine antibodies in the sera of infertile or vasectomized men suggest that some of these individuals may react to the use of protamine sulfate.Fatal anaphylaxis has been reported in one patient with no prior history of allergies.Drug InteractionsProtamine sulfate has been shown to be incompatible with certain antibiotics, including several of the cephalosporins and penicillins (see
DOSAGE & ADMINISTRATION).
Carcinogenesis, Mutagenesis, Impairment of FertilityStudies have not been performed to determine potential for carcinogenicity, mutagenicity or impairment of fertility.PregnancyPregnancy Category C

Animal reproduction studies have not been conducted with protamine sulfate. It is also not known whether protamine sulfate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Protamine sulfate should be given to a pregnant woman only if clearly needed.
Nursing MothersIt is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when protamine sulfate is administered to a nursing woman.Pediatric UseSafety and effectiveness in children have not been established.

Adverse Reactions

The intravenous administration of protamine sulfate may cause a sudden fall in blood pressure and bradycardia. Other reactions include transitory flushing and feeling of warmth, dyspnea, nausea, vomiting and lassitude. Back pain has been reported in conscious patients undergoing such procedures as cardiac catheterization.Severe adverse reactions have been reported including: (1) Anaphylaxis that resulted in severe respiratory distress, circulation collapse and capillary leak (see
PRECAUTIONS). Fatal anaphylaxis has been reported in one patient with no prior history of allergies; (2) Anaphylactoid reactions with circulatory collapse, capillary leak, and noncardiogenic pulmonary edema; acute pulmonary hypertension.
Complement activation by the heparin-protamine complexes, release of lysosomal enzymes from neutrophils, and prostaglandin and thomboxane generation have been associated with the development of anaphylactoid reactions.Severe and potentially irreversible circulatory collapse associated with myocardial failure and reduced cardiac output can also occur. The mechanism(s) of this reaction and the role played by concurrent factors are unclear.High-protein, noncardiogenic pulmonary edema associated with the use of protamine has been reported in patients on cardiopulmonary bypass who are undergoing cardiovascular surgery. The etiologic role of protamine in the pathogenesis of this condition is uncertain, and multiple factors have been present in most cases. The condition has been reported in association with administration of certain blood products, other drugs, cardiopulmonary bypass alone, and other etiologic factors. It is difficult to treat, and it can be life-threatening. Because fatal anaphylactic and anaphylactoid reactions have been reported after the administration of protamine sulfate, the drug should be given only when resuscitation techniques and treatment of anaphyactic and anaphylactoid shock are readily available.

Overdosage

Signs and SymptomsOverdose of protamine sulfate may cause bleeding. Protamine has a weak anticoagulant effect due to an interaction with platelets and with many proteins including fibrinogen. This effect should be distinguished from the rebound anticoagulation that may occur 30 minutes to 18 hours following the reversal of heparin with protamine.Rapid administration of protamine is more likely to result in bradycardia, dyspnea, a sensation of warmth, flushing, and severe hypotension. Hypertension has also occurred.The median lethal dose of protamine sulfate is 50 mg/kg in mice. Serum concentrations of protamine sulfate are not clinically useful. Information is not available on the amount of drug in a single dose that is associated with overdosage or is likely to be life-threatening.TreatmentTo obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians' Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs and unusual drug kinetics in your patient.Replace blood loss with blood transfusions or fresh frozen plasma. If the patient is hypotensive, consider fluids, epinephrine, dobutamine or dopamine.

Dosage & Administration

Each mg of protamine sulfate, calculated on the dried basis, neutralizes not less than 100 USP Heparin Units.Protamine sulfate injection should be given by very slow intravenous injection over a 10-minute period in doses not to exceed 50 mg (see
WARNINGS).
Protamine sulfate is intended for injection without further dilution; however, if further dilution is desired, D5-W or normal saline may be used. Diluted solutions should not be stored since they contain no preservative.Protamine sulfate should not be mixed with other drugs without knowledge of their compatibility, because protamine sulfate has been shown to be incompatible with certain antibiotics, including several of the cephalosporins and penicillins.Because heparin disappears rapidly from the circulation, the dose of protamine sulfate required also decreases rapidly with the time elapsed following intravenous injection of heparin. For example, if the protamine sulfate is administered 30 minutes after the heparin, one-half the usual dose may be sufficient.The dosage of protamine sulfate should be guided by blood coagulation studies (see
WARNINGS).
Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration, whenever solution and container permit.

How Suplied

PROTAMINE SULFATE INJECTION, USP is supplied in the following dosage forms.

NDC 51662-1414-1

PROTAMINE SULFATE INJECTION, USP 50mg/5mL (10mg/mL) 5mL VIAL
HF Acquisition Co LLC, DBA HealthFirst

Mukilteo, WA 98275
Also supplied in the following manufacture supplied dosage formsStore at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Do not permit to freeze.CAUTION: The total dose of protamine sulfate contained in product No. 22925 and 22930 (250 mg in 25 mL) is 5 times greater than in product No. 22905 (50 mg in 5 mL).The large size 25 mL vials are designed for antiheparin treatment only when large doses of heparin have been given during surgery and are to be neutralized by large doses of protamine sulfate after surgical procedures.

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