Drug · FAERS side-effect profile with label screen
Protamine side effects: what 1,837 FDA adverse event reports show
Drug class
Not stated in label
Label matched
Protamine Sulfate (Protamine Sulfate)
closest FDA label found for this product string; brand list suppressed because the label is a related product, not an exact match
Who reports
1,837 reports · 94% serious · 686 with death outcome · 40% female
openFDA FAERS counts, all years, deduplication not applied
Used for
Protamine Sulfate Injection, USP is indicated in the treatment of heparin overdosage.
FDA label, Indications and Usage
What it is
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.
FDA label, Description section
Boxed warning
Protamine sulfate can cause severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension. Risk factors include high dose or overdose.
FDA label
How to read this page. FAERS is a spontaneous-reporting system: counts are not incidence rates and a signal is not proof of causation.
Each reaction below is run through an automated screen — is the term in the FDA label (known), in the indications (the disease being treated), an administrative/coding term, or none of these (unlabeled)?
That screen is mechanical text matching, not a causality assessment. The 30 hand-written Bradford Hill assessments are on the causality assessment page. Not medical advice.
Causality screen of the 40 strongest signals
Labeled — boxed warning 8Labeled (related wording) 3Reporting / coding artifact 5Lab value / disease marker 1Not in label — unassessed 23
What the badges mean
- Labeled — boxed warning The term (or its clinical synonym) appears in the FDA boxed warning: causality is regulator-recognised and considered serious.
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only and flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 27 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
Show:
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Fear | 837 | 364.1 345.8–383.3ROR 668.2 · χ² 293,585 / p <1e-300 | 349.9 EB05 330.4 · IC025 +8.1 3/3 methods agree | Not in label — unassessed | serious PRR 291.9 | no trial data cached |
| Multi-organ failure | 441 | 294.5 271.1–319.9ROR 387.3 · χ² 125,540 / p <1e-300 | 283.5 EB05 262.0 · IC025 +7.6 3/3 methods agree | Not in label — unassessed | serious PRR 175.3 | no trial data cached |
| Renal injury | 729 | 284.3 268.4–301.1ROR 470.9 · χ² 200,748 / p <1e-300 | 275.3 EB05 259.0 · IC025 +7.7 3/3 methods agree | Not in label — unassessed | serious PRR 169.7 | no trial data cached |
| Anhedonia | 625 | 276.1 258.7–294.5ROR 418.0 · χ² 167,132 / p <1e-300 | 267.3 EB05 250.1 · IC025 +7.7 3/3 methods agree | Not in label — unassessed | serious PRR 181.2 | no trial data cached |
| Injury | 971 | 159.1 152.3–166.3ROR 336.7 · χ² 150,813 / p <1e-300 | 156.5 EB05 148.4 · IC025 +7.1 3/3 methods agree | Not in label — unassessed | serious PRR 118.6 | no trial data cached |
| Unevaluable event | 932 | 142.4 136.1–149.1ROR 288.3 · χ² 129,587 / p <1e-300 | 140.3 EB05 132.9 · IC025 +6.9 3/3 methods agree | Reporting / coding artifact | serious PRR 151.7 | no trial data cached |
| Stress | 585 | 93.7 87.6–100.2ROR 137.0 · χ² 53,273 / p <1e-300 | 92.6 EB05 86.5 · IC025 +6.3 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 94.0 | no trial data cached |
| Renal failure (kidney failure) | 1,007 | 86.6 83.1–90.3ROR 190.6 · χ² 85,037 / p <1e-300 | 85.8 EB05 81.5 · IC025 +6.3 3/3 methods agree | Not in label — unassessed | serious PRR 52.8 | no trial data cached |
| Renal impairment | 592 | 81.4 76.1–87.0ROR 119.6 · χ² 46,770 / p <1e-300 | 80.6 EB05 75.3 · IC025 +6.1 3/3 methods agree | Not in label — unassessed | serious PRR 51.2 | no trial data cached |
| Emotional distress | 708 | 66.9 63.2–70.9ROR 108.3 · χ² 45,917 / p <1e-300 | 66.4 EB05 62.4 · IC025 +5.9 3/3 methods agree | Not in label — unassessed | serious PRR 45.7 | no trial data cached |
| Renal failure acute | 180 | 48.0 41.7–55.1ROR 53.1 · χ² 8,211 / p <1e-300 | 47.5 EB05 42.0 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | serious PRR 29.2 | no trial data cached |
| Post procedural haemorrhage | 44 | 43.2 32.2–57.9ROR 44.2 · χ² 1,766 / p <1e-300 | 42.3 EB05 32.8 · IC025 +4.4 3/3 methods agree | Reporting / coding artifact | serious PRR 10.0 · 100% clinician | no trial data cached |
| Cardiogenic shock | 46 | 36.9 27.7–49.1ROR 37.9 · χ² 1,568 / p <1e-300 | 36.3 EB05 28.3 · IC025 +4.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 22.4 | no trial data cached |
| Anxiety | 902 | 36.2 34.6–38.0ROR 70.2 · χ² 31,185 / p <1e-300 | 36.1 EB05 34.2 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious PRR 32.4 | no trial data cached |
| Disability | 47 | 27.2 20.5–36.1ROR 27.9 · χ² 1,158 / p 4e-254 | 26.9 EB05 21.0 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious PRR 17.0 | no trial data cached |
| Pulmonary hypertension | 40 | 21.9 16.1–29.7ROR 22.4 · χ² 776 / p 5e-171 | 21.6 EB05 16.6 · IC025 +3.6 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 12.8 · 97% clinician | no trial data cached |
| Pain | 1,031 | 19.2 18.4–20.0ROR 42.4 · χ² 18,242 / p <1e-300 | 19.1 EB05 18.2 · IC025 +4.1 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 18.5 | no trial data cached |
| Depression | 343 | 17.2 15.6–18.9ROR 20.9 · χ² 5,256 / p <1e-300 | 17.1 EB05 15.7 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious PRR 14.7 | no trial data cached |
| Mucosal inflammation | 36 | 15.8 11.4–21.8ROR 16.1 · χ² 484 / p 1e-107 | 15.6 EB05 11.6 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 10.2 · 97% clinician | no trial data cached |
| Transfusion | 14 | 15.2 9.0–25.7ROR 15.3 · χ² 172 / p 1e-39 | 14.2 EB05 8.3 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 9.7 | no trial data cached |
| Nervousness | 69 | 15.0 11.9–18.9ROR 15.6 · χ² 890 / p 6e-196 | 14.9 EB05 12.1 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious PRR 18.8 | no trial data cached |
| Post procedural complication | 25 | 14.9 10.1–21.9ROR 15.0 · χ² 309 / p 2e-69 | 14.4 EB05 10.0 · IC025 +2.9 3/3 methods agree | Reporting / coding artifact | serious PRR 9.9 | no trial data cached |
| Ventricular fibrillation | 14 | 14.4 8.5–24.2ROR 14.5 · χ² 161 / p 4e-37 | 13.3 EB05 7.7 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 8.1 | no trial data cached |
| Cerebrovascular accident (stroke) | 213 | 14.3 12.6–16.3ROR 16.1 · χ² 2,645 / p <1e-300 | 14.3 EB05 12.7 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious PRR 8.8 | no trial data cached |
| Anaphylactic reaction (severe allergic reaction) | 67 | 13.9 11.0–17.6ROR 14.4 · χ² 793 / p 7e-175 | 13.8 EB05 11.2 · IC025 +3.3 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 8.2 · ♀ 19% (drug 40%) · 94% clinician | no trial data cached |
| Coagulopathy | 18 | 12.4 7.8–19.6ROR 12.5 · χ² 177 / p 1e-40 | 11.4 EB05 7.1 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 7.9 | no trial data cached |
| Disseminated intravascular coagulation | 14 | 11.3 6.7–19.1ROR 11.4 · χ² 122 / p 1e-28 | 9.9 EB05 5.7 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 6.9 | no trial data cached |
| Bronchospasm (airway tightening) | 14 | 11.2 6.6–18.8ROR 11.3 · χ² 120 / p 4e-28 | 9.7 EB05 5.7 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 6.5 | no trial data cached |
| Circulatory collapse | 15 | 10.0 6.1–16.6ROR 10.1 · χ² 113 / p 1e-26 | 8.6 EB05 5.2 · IC025 +2.1 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 6.1 | no trial data cached |
| Emotional disorder | 27 | 9.9 6.8–14.5ROR 10.1 · χ² 209 / p 1e-47 | 9.2 EB05 6.4 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 11.1 | no trial data cached |
| Ventricular tachycardia | 14 | 9.7 5.7–16.3ROR 9.7 · χ² 100 / p 7e-24 | 8.2 EB05 4.9 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 5.5 | no trial data cached |
| Cardiac arrest (heart stopping) | 67 | 9.2 7.3–11.7ROR 9.6 · χ² 486 / p 6e-108 | 8.9 EB05 7.2 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious PRR 5.5 | no trial data cached |
| No therapeutic response | 10 | 9.2 5.0–17.1ROR 9.3 · χ² 65 / p 3e-16 | 7.2 EB05 4.0 · IC025 +1.7 3/3 methods agree | Reporting / coding artifact | serious PRR 6.3 | no trial data cached |
| Hypotension (low blood pressure) | 159 | 9.1 7.8–10.5ROR 9.8 · χ² 1,144 / p 4e-251 | 8.9 EB05 7.8 · IC025 +2.9 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 5.8 · 95% clinician | no trial data cached |
| Bradycardia (slow heart rate) | 36 | 7.7 5.6–10.7ROR 7.9 · χ² 205 / p 8e-47 | 7.2 EB05 5.4 · IC025 +2.3 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 4.1 · ♀ 17% (drug 40%) · 94% clinician | no trial data cached |
| Therapeutic product effect decreased | 30 | 7.7 5.4–11.0ROR 7.8 · χ² 169 / p 6e-39 | 7.1 EB05 5.1 · IC025 +2.2 3/3 methods agree | Reporting / coding artifact | 100% clinician | no trial data cached |
| Blood urea increased | 11 | 7.5 4.1–13.5ROR 7.5 · χ² 55 / p 5e-14 | 6.0 EB05 3.5 · IC025 +1.5 3/3 methods agree | Lab value / disease marker | serious PRR 5.0 | no trial data cached |
| Mental disorder | 27 | 7.1 4.9–10.3ROR 7.2 · χ² 135 / p 2e-31 | 6.4 EB05 4.6 · IC025 +2.0 3/3 methods agree | Labeled (related wording) related wording | serious PRR 5.2 | no trial data cached |
| Shock | 13 | 6.5 3.8–11.2ROR 6.5 · χ² 55 / p 5e-14 | 5.4 EB05 3.3 · IC025 +1.5 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 4.0 | no trial data cached |
| Cardiac disorder | 53 | 6.4 4.9–8.4ROR 6.6 · χ² 239 / p 3e-54 | 6.1 EB05 4.9 · IC025 +2.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 4.5 | no trial data cached |
Trial evidence (ClinicalTrials.gov)
Trial cross-check not yet run for this drug (ClinicalTrials.gov pull covers the 800 most-reported drugs first).
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Pain | 1,031 | 19.2 18.4–20.0ROR 42.4 · χ² 18,242 / p <1e-300 | 19.1 EB05 18.2 · IC025 +4.1 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 18.5 | no trial data cached |
| Renal failure (kidney failure) | 1,007 | 86.6 83.1–90.3ROR 190.6 · χ² 85,037 / p <1e-300 | 85.8 EB05 81.5 · IC025 +6.3 3/3 methods agree | Not in label — unassessed | serious PRR 52.8 | no trial data cached |
| Injury | 971 | 159.1 152.3–166.3ROR 336.7 · χ² 150,813 / p <1e-300 | 156.5 EB05 148.4 · IC025 +7.1 3/3 methods agree | Not in label — unassessed | serious PRR 118.6 | no trial data cached |
| Unevaluable event | 932 | 142.4 136.1–149.1ROR 288.3 · χ² 129,587 / p <1e-300 | 140.3 EB05 132.9 · IC025 +6.9 3/3 methods agree | Reporting / coding artifact | serious PRR 151.7 | no trial data cached |
| Anxiety | 902 | 36.2 34.6–38.0ROR 70.2 · χ² 31,185 / p <1e-300 | 36.1 EB05 34.2 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | serious PRR 32.4 | no trial data cached |
| Fear | 837 | 364.1 345.8–383.3ROR 668.2 · χ² 293,585 / p <1e-300 | 349.9 EB05 330.4 · IC025 +8.1 3/3 methods agree | Not in label — unassessed | serious PRR 291.9 | no trial data cached |
| Renal injury | 729 | 284.3 268.4–301.1ROR 470.9 · χ² 200,748 / p <1e-300 | 275.3 EB05 259.0 · IC025 +7.7 3/3 methods agree | Not in label — unassessed | serious PRR 169.7 | no trial data cached |
| Emotional distress | 708 | 66.9 63.2–70.9ROR 108.3 · χ² 45,917 / p <1e-300 | 66.4 EB05 62.4 · IC025 +5.9 3/3 methods agree | Not in label — unassessed | serious PRR 45.7 | no trial data cached |
| Anhedonia | 625 | 276.1 258.7–294.5ROR 418.0 · χ² 167,132 / p <1e-300 | 267.3 EB05 250.1 · IC025 +7.7 3/3 methods agree | Not in label — unassessed | serious PRR 181.2 | no trial data cached |
| Renal impairment | 592 | 81.4 76.1–87.0ROR 119.6 · χ² 46,770 / p <1e-300 | 80.6 EB05 75.3 · IC025 +6.1 3/3 methods agree | Not in label — unassessed | serious PRR 51.2 | no trial data cached |
| Stress | 585 | 93.7 87.6–100.2ROR 137.0 · χ² 53,273 / p <1e-300 | 92.6 EB05 86.5 · IC025 +6.3 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 94.0 | no trial data cached |
| Death | 448 | 5.9 5.5–6.4ROR 7.5 · χ² 1,915 / p <1e-300 | 5.9 EB05 5.5 · IC025 +2.4 3/3 methods agree | Outcome field, not a reaction boxed warning mentions mortality | serious PRR 3.6 | no trial data cached |
| Multi-organ failure | 441 | 294.5 271.1–319.9ROR 387.3 · χ² 125,540 / p <1e-300 | 283.5 EB05 262.0 · IC025 +7.6 3/3 methods agree | Not in label — unassessed | serious PRR 175.3 | no trial data cached |
| Depression | 343 | 17.2 15.6–18.9ROR 20.9 · χ² 5,256 / p <1e-300 | 17.1 EB05 15.7 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | serious PRR 14.7 | no trial data cached |
| Cerebrovascular accident (stroke) | 213 | 14.3 12.6–16.3ROR 16.1 · χ² 2,645 / p <1e-300 | 14.3 EB05 12.7 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious PRR 8.8 | no trial data cached |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Fear — n=837, PRR 364.1
- Multi-organ failure — n=441, PRR 294.5
- Renal injury — n=729, PRR 284.3
- Anhedonia — n=625, PRR 276.1
- Injury — n=971, PRR 159.1
- Renal failure — n=1,007, PRR 86.6
- Renal impairment — n=592, PRR 81.4
- Emotional distress — n=708, PRR 66.9
- Renal failure acute — n=180, PRR 48.0
- Anxiety — n=902, PRR 36.2
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Protamine?
In FDA FAERS, the most frequently co-reported reaction terms for Protamine are pain, renal failure, injury, anxiety, fear, renal injury. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Protamine have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: Protamine sulfate can cause severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension. Risk factors include high dose or overdose.
Do FAERS signals prove that Protamine causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID c76876da-b9a8-45d0-9278-7df3288d3a06, effective 20250429; matched on
openfda.generic_name.exact:"PROTAMINE SULFATE") - Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 67 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath
Page generated 2026-10-08. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.