Protamine sulfate
protamine
What it isCationic peptide binding heparin; heparin reversal.
Why this oneIt neutralizes unfractionated heparin within minutes, which nothing else does.
What limits itAnaphylaxis, especially after prior protamine-containing insulin or vasectomy. It only partially reverses low molecular weight heparin and can itself cause bleeding in excess.
FDA label
Read the full label on DailyMed ↗
BOXED WARNING Can cause severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension; risk with high/overdose, rapid or repeated administration, prior protamine or protamine-containing drug exposure (NPH/protamine zinc insulin), fish allergy, vasectomy. Keep vasopressors and resuscitation available; do not give without prior heparin use.
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Heparin neutralization | Adults | ~1 mg per 100 USP units of heparin; guided by coagulation studies | 50 mg per slow IV dose (over 10 min) |
Renal Undefined
Hepatic Undefined
Required dose decreases with time elapsed since heparin injection
Instructions
- Give by very slow IV injection over a 10-minute period; do not exceed 50 mg
- Reduce dose as time elapses since heparin (e.g., about half dose if given 30 min after heparin)
- Do not give when bleeding occurs without prior heparin use
- Do not mix with incompatible drugs (certain cephalosporins and penicillins)
Cautions
- Severe hypotension and bradycardia on IV administration
- Fatal anaphylactic and anaphylactoid reactions — resuscitation must be available
- Noncardiogenic (high-protein) pulmonary edema, esp. on cardiopulmonary bypass
- Acute pulmonary hypertension / circulatory collapse
- Higher risk with fish allergy, prior protamine/NPH insulin exposure, vasectomy, LV dysfunction
Adverse reactions
- Sudden fall in blood pressure
- Bradycardia
- Transitory flushing/warmth
- Dyspnea
- Nausea/vomiting
- Lassitude
- Back pain
- Anaphylaxis/anaphylactoid reactions with circulatory collapse and capillary leak
- Noncardiogenic pulmonary edema
- Acute pulmonary hypertension
Pregnancy Undefined
Lactation Undefined
⚠ BOXED WARNING
- Severe hypotension, anaphylaxis and pulmonary hypertension
Classes and tags
Clinical profile
Mechanism of action: Protamine sulfate ballicule
