Hyaluronidase side effects: what 1,184 FDA adverse event reports show

Hyaluronidase · Amphadase · 185 reaction terms · 25,705 drug–reaction co-reports · data 2026-09-14

Drug class

Endoglycosidase

FDA label (Established Pharmacologic Class)

Brand names

Amphadase

openFDA label

Who reports

1,184 reports · 83% serious · 523 with death outcome · 82% female

openFDA FAERS counts, all years, deduplication not applied

Used for

Amphadase ® is an endoglycosidase indicated as an adjuvant: • in subcutaneous fluid administration for achieving hydration ( 1.1 ) • to increase absorption and dispersion of other injected drugs ( 1.2 ) • in subcutaneous urography for improving resorpt.

FDA label, Indications and Usage

What it is

Hyaluronidase is an endoglycosidase. It is a preparation of purified bovine testicular hyaluronidase, a protein enzyme. Hyaluronidase is composed of two major glycosylated forms, α and β. The exact chemical structure of this enzyme is unknown.

FDA label, Description section

Boxed warning

None in the current 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

Reporting / coding artifact 1Lab value / disease marker 2Not in label — unassessed 37

What the badges mean

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. 145 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.

Show: hide coding/lab/outcome terms hide indication terms unlabeled only hide PRR-only

Reaction	Reports	PRR 95% CI · ROR · χ²/p	EBGM EB05 · IC025	Label screen	Serious-only & strata	Trial cross-check
Autoimmune disorder	254	482.9 432.2–539.5ROR 614.5 · χ² 118,439 / p <1e-300	453.8 EB05 408.8 · IC025 +7.7 3/3 methods agree	Not in label — unassessed	serious PRR 346.8 · 96% clinician	no trial data cached
Helicobacter infection	262	467.2 419.1–520.8ROR 599.7 · χ² 118,317 / p <1e-300	440.4 EB05 397.4 · IC025 +7.7 3/3 methods agree	Not in label — unassessed	serious PRR 331.8 · 96% clinician	no trial data cached
Folliculitis	241	423.1 377.4–474.4ROR 531.0 · χ² 98,727 / p <1e-300	400.0 EB05 359.4 · IC025 +7.6 3/3 methods agree	Not in label — unassessed	serious PRR 335.0 · 97% clinician	no trial data cached
Bursitis	237	354.9 316.2–398.2ROR 443.4 · χ² 81,669 / p <1e-300	338.3 EB05 303.7 · IC025 +7.4 3/3 methods agree	Not in label — unassessed	serious PRR 282.5 · 98% clinician	no trial data cached
Hand deformity	243	335.2 299.2–375.4ROR 421.5 · χ² 79,160 / p <1e-300	320.6 EB05 288.1 · IC025 +7.4 3/3 methods agree	Not in label — unassessed	serious PRR 246.8 · 96% clinician	no trial data cached
Pemphigus	218	316.1 280.0–356.9ROR 387.2 · χ² 66,991 / p <1e-300	302.3 EB05 270.1 · IC025 +7.3 3/3 methods agree	Not in label — unassessed	serious PRR 214.9 · 96% clinician	no trial data cached
Joint range of motion decreased	204	274.5 242.0–311.4ROR 331.4 · χ² 54,495 / p <1e-300	263.6 EB05 234.6 · IC025 +7.1 3/3 methods agree	Not in label — unassessed	serious PRR 237.7 · 97% clinician	no trial data cached
Wound infection	160	264.6 228.8–306.0ROR 305.8 · χ² 41,154 / p <1e-300	252.8 EB05 221.6 · IC025 +6.9 3/3 methods agree	Not in label — unassessed	serious PRR 192.9 · 96% clinician	no trial data cached
Sciatica	216	244.5 216.5–276.2ROR 298.9 · χ² 51,463 / p <1e-300	236.1 EB05 210.9 · IC025 +7.1 3/3 methods agree	Not in label — unassessed	serious PRR 223.6 · 96% clinician	no trial data cached
Hypercholesterolaemia	127	238.2 201.9–281.1ROR 266.7 · χ² 29,379 / p <1e-300	227.0 EB05 195.8 · IC025 +6.6 3/3 methods agree	Not in label — unassessed	serious PRR 172.4 · 97% clinician	no trial data cached
Pericarditis	214	230.4 203.9–260.3ROR 281.0 · χ² 48,052 / p <1e-300	222.9 EB05 198.9 · IC025 +7.0 3/3 methods agree	Not in label — unassessed	serious PRR 158.2 · 96% clinician	no trial data cached
Obesity	192	215.7 189.3–245.8ROR 257.3 · χ² 40,352 / p <1e-300	208.7 EB05 185.1 · IC025 +6.9 3/3 methods agree	Not in label — unassessed	serious PRR 170.7 · 98% clinician	no trial data cached
Synovitis	211	209.5 185.2–237.0ROR 254.7 · χ² 43,096 / p <1e-300	203.2 EB05 181.2 · IC025 +6.9 3/3 methods agree	Not in label — unassessed	serious PRR 149.6 · 96% clinician	no trial data cached
Lower limb fracture	221	207.4 184.0–233.7ROR 254.7 · χ² 44,692 / p <1e-300	201.4 EB05 180.1 · IC025 +6.9 3/3 methods agree	Not in label — unassessed	serious PRR 155.4 · 96% clinician	no trial data cached
Laryngitis	124	204.6 173.0–241.9ROR 228.4 · χ² 24,645 / p <1e-300	196.2 EB05 168.9 · IC025 +6.5 3/3 methods agree	Not in label — unassessed	serious n=124 · 96% clinician	no trial data cached
Foot deformity	123	198.5 167.7–234.9ROR 221.4 · χ² 23,714 / p <1e-300	190.5 EB05 163.9 · IC025 +6.5 3/3 methods agree	Not in label — unassessed	serious PRR 157.4 · 94% clinician	no trial data cached
Glossodynia (burning tongue/mouth pain)	233	186.5 166.1–209.4ROR 232.0 · χ² 42,402 / p <1e-300	181.8 EB05 163.1 · IC025 +6.8 3/3 methods agree	Not in label — unassessed	serious PRR 184.4 · 96% clinician	no trial data cached
Fibromyalgia	236	173.8 154.9–194.9ROR 216.8 · χ² 40,018 / p <1e-300	169.7 EB05 152.3 · IC025 +6.8 3/3 methods agree	Not in label — unassessed	serious PRR 156.2 · 97% clinician	no trial data cached
Irritable bowel syndrome	203	169.9 149.8–192.7ROR 204.8 · χ² 33,618 / p <1e-300	165.6 EB05 147.4 · IC025 +6.7 3/3 methods agree	Not in label — unassessed	serious PRR 147.4 · 97% clinician	no trial data cached
Liver injury	200	147.7 130.1–167.7ROR 177.5 · χ² 28,784 / p <1e-300	144.5 EB05 128.4 · IC025 +6.5 3/3 methods agree	Not in label — unassessed	serious PRR 104.8 · 96% clinician	no trial data cached
Pulmonary fibrosis	150	140.1 120.5–162.8ROR 160.3 · χ² 20,431 / p <1e-300	136.6 EB05 119.2 · IC025 +6.3 3/3 methods agree	Not in label — unassessed	serious PRR 96.9 · 98% clinician	no trial data cached
Wound	217	139.3 123.5–157.2ROR 170.3 · χ² 29,464 / p <1e-300	136.6 EB05 122.0 · IC025 +6.5 3/3 methods agree	Not in label — unassessed	serious PRR 113.6 · 95% clinician	no trial data cached
Red blood cell sedimentation rate increased	85	136.8 111.3–168.0ROR 147.3 · χ² 11,239 / p <1e-300	131.8 EB05 109.9 · IC025 +5.9 3/3 methods agree	Lab value / disease marker	serious PRR 106.2 · 93% clinician	no trial data cached
Hepatic cirrhosis	141	134.6 115.2–157.3ROR 152.7 · χ² 18,442 / p <1e-300	131.3 EB05 114.1 · IC025 +6.2 3/3 methods agree	Not in label — unassessed	serious PRR 93.3 · 94% clinician	no trial data cached
Sleep disorder due to a general medical condition	121	133.5 112.7–158.2ROR 148.6 · χ² 15,673 / p <1e-300	129.8 EB05 111.5 · IC025 +6.1 3/3 methods agree	Not in label — unassessed	serious PRR 181.0 · 96% clinician	no trial data cached
Hip arthroplasty	112	131.6 110.2–157.1ROR 145.2 · χ² 14,287 / p <1e-300	127.8 EB05 109.1 · IC025 +6.1 3/3 methods agree	Not in label — unassessed	serious PRR 93.0 · 96% clinician	no trial data cached
Type 2 diabetes mellitus	249	131.5 117.7–147.0ROR 166.3 · χ² 31,938 / p <1e-300	129.3 EB05 116.4 · IC025 +6.5 3/3 methods agree	Not in label — unassessed	serious PRR 94.9 · 96% clinician	no trial data cached
Joint dislocation	75	127.0 102.0–158.3ROR 135.6 · χ² 9,191 / p <1e-300	122.3 EB05 100.8 · IC025 +5.7 3/3 methods agree	Not in label — unassessed	serious PRR 98.0 · 93% clinician	no trial data cached
Impaired healing	227	123.3 109.6–138.6ROR 152.3 · χ² 27,260 / p <1e-300	121.2 EB05 108.5 · IC025 +6.4 3/3 methods agree	Reporting / coding artifact	serious PRR 101.7 · 97% clinician	no trial data cached
Systemic lupus erythematosus	238	120.0 107.0–134.4ROR 149.9 · χ² 27,812 / p <1e-300	118.0 EB05 106.0 · IC025 +6.4 3/3 methods agree	Not in label — unassessed	serious PRR 84.3 · 96% clinician	no trial data cached
Prescribed overdose	119	109.6 92.3–130.0ROR 121.7 · χ² 12,626 / p <1e-300	107.1 EB05 91.9 · IC025 +5.9 3/3 methods agree	Not in label — unassessed	serious PRR 128.2 · 92% clinician	no trial data cached
Night sweats	191	105.7 92.8–120.4ROR 125.8 · χ² 19,612 / p <1e-300	104.0 EB05 92.2 · IC025 +6.1 3/3 methods agree	Not in label — unassessed	serious PRR 124.5 · 96% clinician	no trial data cached
Blood cholesterol increased	265	101.2 91.0–112.6ROR 130.1 · χ² 26,098 / p <1e-300	99.9 EB05 90.2 · IC025 +6.2 3/3 methods agree	Lab value / disease marker	serious PRR 105.3 · 95% clinician	no trial data cached
Weight fluctuation	59	100.8 78.6–129.4ROR 106.1 · χ² 5,703 / p <1e-300	97.2 EB05 78.1 · IC025 +5.3 3/3 methods agree	Not in label — unassessed	serious n=59 · 98% clinician	no trial data cached
Pregnancy	114	100.4 84.3–119.6ROR 111.0 · χ² 11,063 / p <1e-300	98.2 EB05 84.0 · IC025 +5.8 3/3 methods agree	Not in label — unassessed	serious PRR 100.8 · 96% clinician	no trial data cached
Road traffic accident	233	99.1 88.3–111.3ROR 123.2 · χ² 22,453 / p <1e-300	97.8 EB05 87.7 · IC025 +6.1 3/3 methods agree	Not in label — unassessed	serious PRR 79.4 · 96% clinician	no trial data cached
Knee arthroplasty	116	99.1 83.3–117.8ROR 109.7 · χ² 11,112 / p <1e-300	97.0 EB05 83.1 · IC025 +5.8 3/3 methods agree	Not in label — unassessed	serious PRR 70.8 · 97% clinician	no trial data cached
Lower respiratory tract infection	243	95.5 85.3–106.8ROR 119.9 · χ² 22,549 / p <1e-300	94.3 EB05 84.7 · IC025 +6.1 3/3 methods agree	Not in label — unassessed	serious PRR 69.3 · 96% clinician	no trial data cached
Psoriatic arthropathy	211	93.4 82.6–105.6ROR 113.4 · χ² 19,130 / p <1e-300	92.2 EB05 82.2 · IC025 +6.0 3/3 methods agree	Not in label — unassessed	serious PRR 80.7 · 96% clinician	no trial data cached
Osteoarthritis	221	92.6 82.2–104.4ROR 113.7 · χ² 19,875 / p <1e-300	91.4 EB05 81.8 · IC025 +6.0 3/3 methods agree	Not in label — unassessed	serious PRR 71.3 · 95% clinician	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
Abdominal discomfort	297	31.5 28.6–34.8ROR 41.7 · χ² 8,802 / p <1e-300	31.4 EB05 28.5 · IC025 +4.7 3/3 methods agree	Not in label — unassessed	serious PRR 48.8 · 96% clinician	no trial data cached
Alopecia (hair loss)	286	25.8 23.3–28.5ROR 33.7 · χ² 6,841 / p <1e-300	25.7 EB05 23.3 · IC025 +4.4 3/3 methods agree	Not in label — unassessed	serious PRR 37.7 · 95% clinician	no trial data cached
Arthralgia (joint pain)	276	11.8 10.6–13.1ROR 15.1 · χ² 2,772 / p <1e-300	11.8 EB05 10.6 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious PRR 14.8 · 94% clinician	no trial data cached
Hypersensitivity (allergic reaction)	275	26.3 23.7–29.2ROR 34.0 · χ² 6,721 / p <1e-300	26.2 EB05 23.7 · IC025 +4.5 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 29.1 · 95% clinician	no trial data cached
Asthenia (weakness)	274	12.9 11.6–14.3ROR 16.5 · χ² 3,052 / p <1e-300	12.9 EB05 11.6 · IC025 +3.5 3/3 methods agree	Not in label — unassessed	serious PRR 12.6 · 96% clinician	no trial data cached
Hepatic enzyme increased	272	71.2 64.1–79.0ROR 92.1 · χ² 18,732 / p <1e-300	70.5 EB05 63.8 · IC025 +5.8 3/3 methods agree	Lab value / disease marker	serious PRR 70.8 · 96% clinician	no trial data cached
Hypertension (high blood pressure)	271	22.7 20.4–25.2ROR 29.1 · χ² 5,640 / p <1e-300	22.6 EB05 20.4 · IC025 +4.2 3/3 methods agree	Not in label — unassessed	serious PRR 19.4 · 96% clinician	no trial data cached
Blood cholesterol increased	265	101.2 91.0–112.6ROR 130.1 · χ² 26,098 / p <1e-300	99.9 EB05 90.2 · IC025 +6.2 3/3 methods agree	Lab value / disease marker	serious PRR 105.3 · 95% clinician	no trial data cached
Discomfort	264	77.5 69.6–86.2ROR 99.4 · χ² 19,818 / p <1e-300	76.7 EB05 69.3 · IC025 +5.9 3/3 methods agree	Not in label — unassessed	serious PRR 93.0 · 96% clinician	no trial data cached
Asthma	262	41.5 37.3–46.2ROR 53.0 · χ² 10,343 / p <1e-300	41.3 EB05 37.3 · IC025 +5.1 3/3 methods agree	Not in label — unassessed	serious PRR 40.2 · 96% clinician	no trial data cached
Helicobacter infection	262	467.2 419.1–520.8ROR 599.7 · χ² 118,317 / p <1e-300	440.4 EB05 397.4 · IC025 +7.7 3/3 methods agree	Not in label — unassessed	serious PRR 331.8 · 96% clinician	no trial data cached
Contusion	260	48.0 43.1–53.5ROR 61.3 · χ² 11,947 / p <1e-300	47.7 EB05 43.1 · IC025 +5.3 3/3 methods agree	Not in label — unassessed	serious PRR 56.9 · 96% clinician	no trial data cached
Decreased appetite (loss of appetite)	258	19.7 17.7–22.0ROR 25.0 · χ² 4,620 / p <1e-300	19.7 EB05 17.8 · IC025 +4.0 3/3 methods agree	Not in label — unassessed	serious PRR 20.7 · 94% clinician	no trial data cached
Dizziness	256	9.1 8.2–10.2ROR 11.3 · χ² 1,884 / p <1e-300	9.0 EB05 8.1 · IC025 +3.0 3/3 methods agree	Not in label — unassessed	serious PRR 11.2 · 96% clinician	no trial data cached
Confusional state (confusion)	255	27.9 25.1–31.1ROR 35.3 · χ² 6,637 / p <1e-300	27.8 EB05 25.1 · IC025 +4.5 3/3 methods agree	Not in label — unassessed	serious PRR 24.4 · 96% clinician	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.

Autoimmune disorder — n=254, PRR 482.9
Helicobacter infection — n=262, PRR 467.2
Folliculitis — n=241, PRR 423.1
Bursitis — n=237, PRR 354.9
Hand deformity — n=243, PRR 335.2
Pemphigus — n=218, PRR 316.1
Joint range of motion decreased — n=204, PRR 274.5
Wound infection — n=160, PRR 264.6
Sciatica — n=216, PRR 244.5
Hypercholesterolaemia — n=127, PRR 238.2

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 Hyaluronidase?

In FDA FAERS, the most frequently co-reported reaction terms for Hyaluronidase are abdominal discomfort, alopecia, arthralgia, hypersensitivity, asthenia, hepatic enzyme increased. 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 Hyaluronidase have an FDA boxed warning?

No. The FDA label retrieved for Hyaluronidase has no boxed warning; see the label's Warnings and Precautions for the recognised risks.

Do FAERS signals prove that Hyaluronidase 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 8396ea96-7cb5-4e26-87a4-90bca9c3c6dd, effective 20240201; matched on openfda.generic_name.exact:"HYALURONIDASE")
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, field patient.drug.openfda.generic_name.exact, 185 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.