Protamine Sulfate
10 mg/mL · Injection, Solution
- Prescription only
- Heparin Reversal Agent
- Active substance
- Protamine Sulfate
- Used in
- Blood, clotting and anaemia
- Made by
- HF Acquisition Co LLC, DBA HealthFirst
- Source
- Official label
Quoted from the official source. Not yet reviewed by Mediclarum — the leaflet in your pack is authoritative.
At a glance
Quoted from the official label · 2024-01-22
Heparin Reversal Agent
- Protamine Sulfate Injection, USP is indicated in the treatment of heparin overdosage.
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 ).
Full directions ↓Protamine sulfate is contraindicated in patients who have shown previous intolerance to the drug.
All warnings ↓- Prescription only
- FDA enforcement reports list no ongoing recall, and none from the last two years, for this product code · checked 2026-10-02
Every line above is selected, not written, from the official label. Nothing is reworded. DailyMed
What it is for
- Protamine Sulfate Injection, USP is indicated in the treatment of heparin overdosage.
From the official label · 2024-01-22 · DailyMed
How it works
From this product’s own US prescribing label.
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.
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.
Quoted from the prescribing label, sections “Mechanism of Action” and “Pharmacokinetics”. DailyMed · 2024-01-22
Serious warning
The strongest warning the FDA requires. It is printed in a box at the top of the label.
BOXED WARNING
Quoted from the official label, section “Boxed Warning”.
Do not take it if
Protamine sulfate is contraindicated in patients who have shown previous intolerance to the drug.
Quoted from the official label, section “Contraindications”.
How to take it
These directions are for this exact strength and form. Another one is different.
- 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.
Quoted from the official label, section “Dosage & Administration”.
Other 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.
- General Because 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.
- Drug Interactions Protamine sulfate has been shown to be incompatible with certain antibiotics, including several of the cephalosporins and penicillins (see DOSAGE & ADMINISTRATION ).
- Carcinogenesis, Mutagenesis, Impairment of Fertility Studies have not been performed to determine potential for carcinogenicity, mutagenicity or impairment of fertility.
- Pregnancy Pregnancy 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 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 protamine sulfate is administered to a nursing woman.
- Pediatric Use Safety and effectiveness in children have not been established.
Quoted from the official label, section “Warnings”.
If you take too much
In an emergency, call your local emergency number or a poison control centre.
- Signs and Symptoms Overdose 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.
- Treatment To 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.
Quoted from the official label, section “Overdosage”.
Side effects
- 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.
Quoted from the official label, section “Adverse Reactions”.
What it looks like and how it is packed
- 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 NDC 51662-1414-2 PROTAMINE SULFATE INJECTION, USP 50mg/5mL (10mg/mL) 5mL VIAL in a POUCH NDC 51662-1414-3 PROTAMINE SULFATE INJECTION, USP 50mg/5mL (10mg/mL) 5mL VIAL in a POUCH, 25 Pouches in a Case HF Acquisition Co LLC, DBA HealthFirst Mukilteo, WA 98275
- Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
- Do not permit to freeze.
- Also supplied in the following manufacture supplied dosage forms 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.
- How Supplied
Quoted from the official label, section “How Supplied”.
What is in it
- 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.
Quoted from the official label, section “Description”.
Ingredients people check for
Lactose, gluten, dyes, sugars and other ingredients that matter with an allergy, intolerance or diet — as this product’s FDA label lists them.
The stored label for this product has no list of inactive ingredients. The list on the pack is the one to check.
Quoted from the FDA label. A label that does not name an ingredient is not a guarantee that the product is free of it, and formulations change. With an allergy, check the pack and ask a pharmacist.
Every version of this medicine (2)
The same active substance, strength and kind of form, from every company that sells it — with what each label lists.
Showing 2 of 2
Same active substance, strength and form in other countries
Matched on active substance, strength and kind of form only. This is not a statement that the products are equivalent or interchangeable: other ingredients, release and approved uses can differ — ask a pharmacist before swapping.
Medicine passport: one printable page to show a pharmacist abroad
CanadaNo exact match for this strength and form
Details
| Made by | HF Acquisition Co LLC, DBA HealthFirst |
|---|---|
| Active substance | Protamine Sulfate |
| Used in | Blood, clotting and anaemia |
| Strength | 10 mg/mL |
| Form | Injection, Solution |
| Route | Intravenous |
| Packs | 5 mL in 1 VIAL, SINGLE-DOSE · 25 POUCH in 1 CASE / 1 VIAL, SINGLE-DOSE in 1 POUCH / 5 mL in 1 VIAL, SINGLE-DOSE |
| NDC | 51662-1414 |
Source: NDC Directory · 2026-09-13 · not reviewed by a clinician
Source: US Food and Drug Administration, NDC Directory. Reuse terms: US government work (FDA).
Other strengths and forms
2 products are sold under this name. Grouped by form; a number on a strength means several companies make it.
- Injection, Solution2 products
10 mg/mL2
10 mg/mL · 2 companies
- Fresenius Kabi USA, LLC
- HF Acquisition Co LLC, DBA HealthFirst · this page
Same active substance
These contain the same substance. That does not mean one can replace another — ask a pharmacist.