Drug information of Protamine sulfat
Protamine sulfate is a drug that reverses the anticoagulant effects of heparin by binding to it. It was originally isolated from the sperm of salmon and other species of fish but is now produced primarily through recombinant biotechnology. Protamine sulfate was approved for medical use in the United States in 1969.
Mechanism of effect
It is a highly cationic peptide that binds to either heparin or low molecular weight heparin (LMWH) to form a stable ion pair, which does not have anticoagulant activity. The ionic complex is then removed and broken down by the reticuloendothelial system. In large doses, protamine sulfate may also have an independent—however weak—anticoagulant effect.
Protamine sulphate 1% demonstrates activity neutralising anticoagulant properties of heparin, creating the complex heparin/protamine. Activity of protamine (towards heparin) takes place within five minutes after intravenous injection of the preparation.
Half-life elimination: 7 min
Onset: 5 min
Duration: 2 hr
Vd: 5.4 L
Clearance: 1.4 L/min
- 10 mg/mL
1-1.5 mg per 100 USP units of heparin; not to exceed 50 mg
Monitor APTT 5-15 min after dose then in 2-8 hr
In accidental overdoses of heparin, consider t1/2 heparin 60-90 min
Complex of protamine and heparin may degrade over time requiring further doses
Dalteparin or Tinzaparin Overdose
1 mg protamine for 100 units dalteparin or tinzaparin; if PTT prolonged 4hr after protamine overdose administer 0.5 mg per 100 units of dalteparin or tinzaparin
1 mg per mg enoxaparin (if enoxaparin overdose given within 8 hr); if >8 hr of overdose or bleeding continues after 4 hr after first dose, give 0.5 mg protamine per mg enoxaparin
Time Elapsed Since Heparin Dose
Dose of protamine (mg) to neutralize 100 units of heparin
- <1/2 hr: 1-1.5 mg/100 units of heparin
- 30-120 min: 0.5-0.75 mg/100 units of heparin
- >2 hr: 0.25-0.375 mg/100 units of heparin
- 10 mg/mL
Heparin Neutralization (Off-label)
~1 mg protamine neutralizes 100 units of heparin; not to exceed 50 mg/dose
Monagle P, et al. Chest 2008:133(6 Suppl):S887-S968
Time elapsed since heparin dose
- Protamine dose to neutralize 100 units of heparin
- <1/2 hr: 1 mg
- 30-120 min: 0.5-0.75 mg
- >2 hr: 0.25-0.375 mg
Drug contraindicationshypersensitivity to this drug
InteractionsAzathioprine , Azithromycin , Allopurinol , Eptifibatide , Erythromycin , Steradiol , Estrogen cojugated , Enoxaparin , Budesonide , Prasugrel , Tanacetum parthenium , Feverfew , Vitamin E , Glucagon , Netonal , Triphasic , Primidone , Ticlopidine , Dipyridamole , Sulfadiazine , Cilostazol , Phenobarbital , Levothyroxine , Heparin , Warfarin , Capecitabine , Carbamazepine , Clarithromycin , Clopidogrel , Aspirin , Liothyronine , Hexobarbital , Pentobarbital , Amobarbital , Phenindione , Bivalirudin , Argatroban , Lepirudin , Mifepristone , Tirofiban , Anagrelide , Butalbital and Acetaminophen , Dalteparin , Aceclofenac , Celecoxib , Acemetacin , Chitosan , Tinzaparin , Agrimony , Azapropazone , Butabarbital , Antithrombin alfa , Cefamandole , Secobarbital , Roxithromycin , tibolone , bazedoxifene/conjugated estrogens , fondaparinux
Black Box Warnings
- Protamine sulfate can cause severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension
- Risk factors include high dose or overdose, rapid administration, repeated doses, previous administration of protamine, and current or previous use of protamine-containing drugs (NPH insulin, protamine zinc insulin, and certain beta-blockers).
- Allergy to fish, previous vasectomy, severe left ventricular dysfunction, and abnormal preoperative pulmonary hemodynamics also may be risk factors. In patients with any of these risk factors, the risk to benefit of administration of protamine sulfate should be carefully considered. Vasopressors and resuscitation equipment should be immediately available in case of a severe reaction to protamine.
- Protamine should not be given when bleeding occurs without prior heparin use
Points of recommendation
- This medicine may cause very low blood pressure or very bad heart or lung problems. Sometimes, these may be deadly. Tell your doctor if you have heart or lung problems, if you have had a vasectomy, or if you have an allergyto fish. Talk with your doctor.
- This medicine is not for use when bleeding happens without heparin use. Talk with the doctor.
- Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
- Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.
- Importance of informing patients of other important precautionary information.
- It is given as a shot into a vein over a period of time.
- You will be watched closely by your doctor.