Collagenase Clostridium Histolyticum side effects: what 5,258 FDA adverse event reports show
Drug class
Combination of bacterial collagenases
Brand names
Xiaflex
Who reports
5,258 reports · 26% serious · 60 with death outcome · 8% female
Used for
XIAFLEX is indicated for the treatment of adult patients with Dupuytren’s contracture with a palpable cord. XIAFLEX is indicated for the treatment of adult men with Peyronie’s disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy.
What it is
XIAFLEX contains purified collagenase clostridium histolyticum, consisting of two microbial collagenases in a defined mass ratio, Collagenase AUX-I and Collagenase AUX-II, which are isolated and purified from the fermentation of Clostridium histolyticum bacteria.
Boxed warning
CORPORAL RUPTURE (PENILE FRACTURE) OR OTHER SERIOUS PENILE INJURY IN THE TREATMENT OF PEYRONIE’S DISEASE Corporal rupture (penile fracture) was reported as an adverse reaction in 5 of 1044 (0.5%) XIAFLEX-treated patients in clinical studies.
Causality screen of the 40 strongest signals
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 adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
- 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.
- 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. 46 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Laceration | 85 | 34.8 28.2–43.0ROR 35.3 · χ² 2,734 / p <1e-300 | 34.3 EB05 28.6 · IC025 +4.5 3/3 methods agree | Labeled — boxed warning exact term | serious n=35 | no trial data cached |
| Contusion | 670 | 27.2 25.3–29.2ROR 30.9 · χ² 16,818 / p <1e-300 | 27.0 EB05 25.3 · IC025 +4.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 11.0 · 71% consumer | no trial data cached |
| Tendon rupture (torn tendon) | 82 | 25.8 20.8–32.0ROR 26.2 · χ² 1,919 / p <1e-300 | 25.5 EB05 21.2 · IC025 +4.1 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 63.4 · ♀ 51% (drug 8%) | no trial data cached |
| Swelling | 576 | 24.0 22.2–26.0ROR 26.8 · χ² 12,664 / p <1e-300 | 23.9 EB05 22.3 · IC025 +4.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 8.8 · 78% consumer | no trial data cached |
| Nodule | 75 | 22.4 17.9–28.0ROR 22.7 · χ² 1,502 / p <1e-300 | 22.1 EB05 18.2 · IC025 +3.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.3 · 83% consumer | no trial data cached |
| Skin laceration | 61 | 22.0 17.1–28.2ROR 22.2 · χ² 1,195 / p 4e-262 | 21.7 EB05 17.5 · IC025 +3.8 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 27.3 | no trial data cached |
| Haematoma | 141 | 21.1 17.9–24.8ROR 21.6 · χ² 2,668 / p <1e-300 | 20.9 EB05 18.2 · IC025 +4.0 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 10.7 | no trial data cached |
| Tenderness | 43 | 16.0 11.9–21.6ROR 16.1 · χ² 588 / p 4e-130 | 15.8 EB05 12.1 · IC025 +3.3 3/3 methods agree | Labeled adverse reaction exact term | serious n=7 | no trial data cached |
| Procedural pain | 101 | 14.2 11.7–17.2ROR 14.4 · χ² 1,222 / p 5e-268 | 14.1 EB05 11.9 · IC025 +3.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.5 · 83% consumer | no trial data cached |
| Injection site haematoma | 46 | 12.2 9.1–16.3ROR 12.3 · χ² 460 / p 2e-102 | 11.9 EB05 9.1 · IC025 +2.9 3/3 methods agree | Labeled adverse reaction exact term | serious n=12 | no trial data cached |
| Injection site nodule | 33 | 11.7 8.3–16.4ROR 11.7 · χ² 310 / p 9e-70 | 11.1 EB05 8.1 · IC025 +2.7 3/3 methods agree | Labeled (related wording) related wording | serious n=3 · 85% consumer | no trial data cached |
| Injection site swelling | 213 | 10.9 9.6–12.4ROR 11.3 · χ² 1,909 / p <1e-300 | 10.8 EB05 9.6 · IC025 +3.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 25.7 | no trial data cached |
| Erectile dysfunction | 67 | 10.1 8.0–12.8ROR 10.2 · χ² 539 / p 1e-119 | 9.8 EB05 7.9 · IC025 +2.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 14.3 | no trial data cached |
| Skin discolouration | 117 | 9.9 8.3–11.8ROR 10.1 · χ² 925 / p 2e-203 | 9.7 EB05 8.3 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 8.1 · 79% consumer | no trial data cached |
| Injection site bruising | 191 | 9.4 8.2–10.8ROR 9.7 · χ² 1,427 / p <1e-300 | 9.3 EB05 8.2 · IC025 +3.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 21.1 · 75% consumer | no trial data cached |
| Drug effect less than expected | 31 | 8.5 6.0–12.1ROR 8.6 · χ² 198 / p 2e-45 | 7.8 EB05 5.7 · IC025 +2.3 3/3 methods agree | Reporting / coding artifact | serious n=2 · 77% consumer | no trial data cached |
| Injection site discolouration | 26 | 8.1 5.5–11.9ROR 8.2 · χ² 155 / p 6e-36 | 7.3 EB05 5.2 · IC025 +2.2 3/3 methods agree | Labeled (related wording) related wording | serious n=6 · 84% consumer | no trial data cached |
| Mass | 27 | 7.5 5.1–10.9ROR 7.5 · χ² 145 / p 1e-33 | 6.8 EB05 4.8 · IC025 +2.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.7 | no trial data cached |
| Lymphadenopathy | 64 | 7.0 5.5–8.9ROR 7.1 · χ² 323 / p 1e-72 | 6.7 EB05 5.4 · IC025 +2.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.2 · ♀ 38% (drug 8%) | no trial data cached |
| Injection site discomfort | 18 | 6.8 4.3–10.7ROR 6.8 · χ² 83 / p 5e-20 | 5.9 EB05 3.9 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious n=7 | no trial data cached |
| Disease recurrence | 72 | 5.8 4.6–7.4ROR 5.9 · χ² 285 / p 3e-64 | 5.6 EB05 4.6 · IC025 +2.1 3/3 methods agree | Reporting / coding artifact | serious PRR 6.2 | no trial data cached |
| Dysuria (painful urination) | 47 | 4.9 3.7–6.6ROR 5.0 · χ² 144 / p 2e-33 | 4.7 EB05 3.7 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 3.6 · 82% consumer | no trial data cached |
| Discomfort | 74 | 4.7 3.8–5.9ROR 4.8 · χ² 214 / p 8e-49 | 4.6 EB05 3.8 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.3 · 72% consumer | no trial data cached |
| Inappropriate schedule of product administration | 212 | 4.6 4.1–5.3ROR 4.8 · χ² 608 / p 2e-134 | 4.6 EB05 4.1 · IC025 +2.0 3/3 methods agree | Reporting / coding artifact | serious PRR 2.5 · 74% consumer | no trial data cached |
| Inappropriate schedule of drug administration | 82 | 4.4 3.6–5.5ROR 4.5 · χ² 213 / p 2e-48 | 4.3 EB05 3.6 · IC025 +1.7 3/3 methods agree | Reporting / coding artifact | serious PRR 9.4 | no trial data cached |
| Blister | 62 | 4.3 3.3–5.5ROR 4.3 · χ² 153 / p 2e-35 | 4.2 EB05 3.4 · IC025 +1.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.1 | no trial data cached |
| Peripheral swelling | 164 | 4.1 3.6–4.8ROR 4.2 · χ² 390 / p 4e-87 | 4.1 EB05 3.6 · IC025 +1.8 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.8 · ♀ 42% (drug 8%) | no trial data cached |
| Therapeutic product effect decreased | 47 | 4.1 3.1–5.5ROR 4.1 · χ² 107 / p 2e-25 | 4.0 EB05 3.1 · IC025 +1.5 3/3 methods agree | Reporting / coding artifact | 83% consumer | no trial data cached |
| Injection site pain (pain where injected) | 321 | 4.1 3.7–4.6ROR 4.3 · χ² 759 / p 2e-167 | 4.1 EB05 3.7 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 10.3 · 71% consumer | no trial data cached |
| Product administration error | 21 | 4.1 2.7–6.2ROR 4.1 · χ² 46 / p 7e-12 | 3.8 EB05 2.6 · IC025 +1.2 3/3 methods agree | Reporting / coding artifact | serious PRR 3.3 | no trial data cached |
| Drug ineffective (drug did not work) | 1,358 | 4.0 3.8–4.2ROR 5.0 · χ² 3,249 / p <1e-300 | 4.0 EB05 3.8 · IC025 +1.9 3/3 methods agree | Reporting / coding artifact | serious PRR 1.3 · 71% consumer | no trial data cached |
| Scar | 17 | 3.8 2.4–6.2ROR 3.8 · χ² 33 / p 5e-9 | 3.5 EB05 2.3 · IC025 +1.0 3/3 methods agree | Not in label — unassessed | serious PRR 7.9 | no trial data cached |
| Joint range of motion decreased | 13 | 3.8 2.2–6.5ROR 3.8 · χ² 24 / p 6e-7 | 3.4 EB05 2.1 · IC025 +0.8 3/3 methods agree | Not in label — unassessed | serious PRR 5.1 | no trial data cached |
| Incorrect product administration duration | 18 | 3.4 2.2–5.5ROR 3.4 · χ² 29 / p 4e-8 | 3.2 EB05 2.2 · IC025 +0.9 3/3 methods agree | Reporting / coding artifact | serious n=2 | no trial data cached |
| Drug effect decreased | 48 | 3.4 2.6–4.5ROR 3.4 · χ² 79 / p 3e-19 | 3.3 EB05 2.6 · IC025 +1.3 3/3 methods agree | Reporting / coding artifact | serious PRR 1.7 | no trial data cached |
| Pain | 506 | 3.2 2.9–3.5ROR 3.4 · χ² 779 / p 1e-171 | 3.2 EB05 3.0 · IC025 +1.5 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 1.0 · 82% consumer | no trial data cached |
| Pelvic pain | 14 | 3.0 1.8–5.0ROR 3.0 · χ² 17 / p 2e-5 | 2.8 EB05 1.8 · IC025 +0.6 | Not in label — unassessed | serious PRR 3.3 | no trial data cached |
| Wrong technique in product usage process | 151 | 2.9 2.5–3.4ROR 3.0 · χ² 187 / p 6e-43 | 2.9 EB05 2.5 · IC025 +1.3 3/3 methods agree | Reporting / coding artifact | serious PRR 4.5 | no trial data cached |
| Treatment noncompliance | 40 | 2.9 2.1–3.9ROR 2.9 · χ² 46 / p 5e-12 | 2.8 EB05 2.1 · IC025 +1.0 3/3 methods agree | Reporting / coding artifact | serious PRR 6.6 | no trial data cached |
| Condition aggravated | 208 | 2.7 2.3–3.0ROR 2.7 · χ² 218 / p 1e-49 | 2.7 EB05 2.4 · IC025 +1.2 3/3 methods agree | Reporting / coding artifact | serious PRR 1.5 · 76% consumer | no trial data cached |
Trial evidence (ClinicalTrials.gov)
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 |
|---|---|---|---|---|---|---|
| Drug ineffective (drug did not work) | 1,358 | 4.0 3.8–4.2ROR 5.0 · χ² 3,249 / p <1e-300 | 4.0 EB05 3.8 · IC025 +1.9 3/3 methods agree | Reporting / coding artifact | serious PRR 1.3 · 71% consumer | no trial data cached |
| Contusion | 670 | 27.2 25.3–29.2ROR 30.9 · χ² 16,818 / p <1e-300 | 27.0 EB05 25.3 · IC025 +4.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 11.0 · 71% consumer | no trial data cached |
| Swelling | 576 | 24.0 22.2–26.0ROR 26.8 · χ² 12,664 / p <1e-300 | 23.9 EB05 22.3 · IC025 +4.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 8.8 · 78% consumer | no trial data cached |
| Pain | 506 | 3.2 2.9–3.5ROR 3.4 · χ² 779 / p 1e-171 | 3.2 EB05 3.0 · IC025 +1.5 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 1.0 · 82% consumer | no trial data cached |
| Injection site pain (pain where injected) | 321 | 4.1 3.7–4.6ROR 4.3 · χ² 759 / p 2e-167 | 4.1 EB05 3.7 · IC025 +1.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 10.3 · 71% consumer | no trial data cached |
| Injection site swelling | 213 | 10.9 9.6–12.4ROR 11.3 · χ² 1,909 / p <1e-300 | 10.8 EB05 9.6 · IC025 +3.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 25.7 | no trial data cached |
| Inappropriate schedule of product administration | 212 | 4.6 4.1–5.3ROR 4.8 · χ² 608 / p 2e-134 | 4.6 EB05 4.1 · IC025 +2.0 3/3 methods agree | Reporting / coding artifact | serious PRR 2.5 · 74% consumer | no trial data cached |
| Condition aggravated | 208 | 2.7 2.3–3.0ROR 2.7 · χ² 218 / p 1e-49 | 2.7 EB05 2.4 · IC025 +1.2 3/3 methods agree | Reporting / coding artifact | serious PRR 1.5 · 76% consumer | no trial data cached |
| Injection site bruising | 191 | 9.4 8.2–10.8ROR 9.7 · χ² 1,427 / p <1e-300 | 9.3 EB05 8.2 · IC025 +3.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 21.1 · 75% consumer | no trial data cached |
| Pain in extremity | 187 | 2.5 2.1–2.8ROR 2.5 · χ² 162 / p 2e-37 | 2.4 EB05 2.2 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.1 · ♀ 39% (drug 8%) | no trial data cached |
| Peripheral swelling | 164 | 4.1 3.6–4.8ROR 4.2 · χ² 390 / p 4e-87 | 4.1 EB05 3.6 · IC025 +1.8 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.8 · ♀ 42% (drug 8%) | no trial data cached |
| Wrong technique in product usage process | 151 | 2.9 2.5–3.4ROR 3.0 · χ² 187 / p 6e-43 | 2.9 EB05 2.5 · IC025 +1.3 3/3 methods agree | Reporting / coding artifact | serious PRR 4.5 | no trial data cached |
| Haematoma | 141 | 21.1 17.9–24.8ROR 21.6 · χ² 2,668 / p <1e-300 | 20.9 EB05 18.2 · IC025 +4.0 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 10.7 | no trial data cached |
| Skin discolouration | 117 | 9.9 8.3–11.8ROR 10.1 · χ² 925 / p 2e-203 | 9.7 EB05 8.3 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 8.1 · 79% consumer | no trial data cached |
| Procedural pain | 101 | 14.2 11.7–17.2ROR 14.4 · χ² 1,222 / p 5e-268 | 14.1 EB05 11.9 · IC025 +3.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.5 · 83% consumer | 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.
- Skin discolouration — n=117, PRR 9.9
- Dysuria — n=47, PRR 4.9
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 Collagenase Clostridium Histolyticum?
In FDA FAERS, the most frequently co-reported reaction terms for Collagenase Clostridium Histolyticum are contusion, swelling, pain, injection site pain, injection site swelling, injection site bruising. 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 Collagenase Clostridium Histolyticum have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: CORPORAL RUPTURE (PENILE FRACTURE) OR OTHER SERIOUS PENILE INJURY IN THE TREATMENT OF PEYRONIE’S DISEASE Corporal rupture (penile fracture) was reported as an adverse reaction in 5 of 1044 (0.5%) XIAFLEX-treated patients in clinical studies.
Do FAERS signals prove that Collagenase Clostridium Histolyticum 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 805cecd0-fd1f-11dd-87af-0800200c9a66, effective 20260422; matched on
openfda.generic_name.exact:"COLLAGENASE CLOSTRIDIUM HISTOLYTICUM") - 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, 86 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.