protamine sulfate
Brand: Protamine Sulfate Injection
Prototype Drug
Drug Class: anticoagulant reversal agent
Drug Family: reversal agent
Subclass: polycationic heparin antagonist
Organ Systems: cardiovascularhematology-oncology
Mechanism of Action
Strongly basic polycationic protein from fish sperm; binds negatively-charged heparin forming stable inactive complex; reverses heparin anticoagulation.
heparin (ionic binding — reversal)
Indications
- reversal of UFH
- partial reversal of LMWH (60-80%)
- heparin rebound after CPB
Contraindications
- fish/protamine allergy (higher risk of reactions)
- diabetics using NPH insulin (higher sensitivity)
Adverse Effects
Common
- hypotension
- bradycardia
- anaphylaxis
- flushing
Serious
- severe anaphylaxis/anaphylactoid reaction
- pulmonary hypertension (IV rapid)
- heparin rebound
Pharmacokinetics (ADME)
| Absorption | IV only |
| Distribution | intravascular |
| Metabolism | proteolysis |
| Excretion | renal |
| Half-life | short (~5 min effect duration) |
| Onset | immediate |
| Peak | immediate |
| Duration | 2 hours |
| Protein Binding | low |
| Vd | low |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| heparin | specific antagonism — beneficial reversal | beneficial |
Nursing Considerations
- 1 mg protamine reverses approximately 100 units UFH given in last 2-3 hours
- Administer slowly IV over 10 minutes to reduce hypotension and bradycardia
- Monitor aPTT after administration
- Fish allergy or prior NPH insulin use increases anaphylaxis risk — have resuscitation ready
- LMWH: protamine reverses only ~60-80% of anti-Xa activity
Clinical Pearls
- Excess protamine itself has anticoagulant effects (paradoxically)
- Heparin rebound: heparin re-released from tissue stores hours after protamine reversal — monitor INR/aPTT
Safety Profile
Pregnancy use-with-caution
Lactation insufficient-data
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.