Drug · FAERS side-effect profile with label screen

Buprenorphine and Naloxone side effects: what 23,980 FDA adverse event reports show

Buprenorphine Hydrochloride, Naloxone Hydrochloride · 1,130 reaction terms · 94,042 drug–reaction co-reports · data 2026-09-14

Drug class

Partial Opioid Agonist

FDA label (Established Pharmacologic Class) of the closest related product

Label matched

Buprenorphine (Buprenorphine)

closest FDA label found for this product string; brand list suppressed because the label is a related product, not an exact match

Who reports

23,980 reports · 63% serious · 1,263 with death outcome · 50% female

openFDA FAERS counts, all years, deduplication not applied

Used for

Buprenorphine transdermal system is indicated for the management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate release opioids. Limitations of Use Bec.

FDA label, Indications and Usage

What it is

Buprenorphine transdermal system is a transdermal system providing systemic delivery of buprenorphine, a mu opioid partial agonist analgesic, continuously for 7 days.

FDA label, Description section

Boxed warning

SERIOUS AND LIFE-THREATENING RISKS FROM USE OF BUPRENORPHINE TRANSDERMAL SYSTEM Addiction, Abuse, and Misuse Because the use of buprenorphine transdermal system exposes patients and other users to the risks of opioid.

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 adverse reaction 2Labeled (related wording) 6Reporting / coding artifact 12Not in label — unassessed 20

What the badges mean

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. 1,090 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
Drug detoxification	258	357.5 309.3–413.1ROR 361.3 · χ² 64,572 / p <1e-300	248.3 EB05 223.9 · IC025 +7.2 3/3 methods agree	Not in label — unassessed	serious n=251 · 72% consumer	NCT00723697: 2/1,305 (0.2%) on Buprenorphine and Naloxone (serious AE)
Tooth erosion	295	306.3 268.3–349.6ROR 310.1 · χ² 66,006 / p <1e-300	223.0 EB05 202.4 · IC025 +7.2 3/3 methods agree	Not in label — unassessed	serious n=149 · 82% consumer	not reported in cached trials
Inappropriate schedule of product discontinuation	125	284.2 232.3–347.8ROR 285.7 · χ² 26,317 / p <1e-300	207.2 EB05 178.5 · IC025 +6.6 3/3 methods agree	Reporting / coding artifact	serious n=30 · 90% consumer	not reported in cached trials
Therapy naive	20	175.9 108.7–284.4ROR 176.0 · χ² 2,745 / p <1e-300	128.6 EB05 87.9 · IC025 +4.3 3/3 methods agree	Not in label — unassessed	serious n=13	not reported in cached trials
Intentional underdose	1,027	143.6 134.5–153.2ROR 149.9 · χ² 124,548 / p <1e-300	122.9 EB05 116.7 · IC025 +6.8 3/3 methods agree	Not in label — unassessed	serious n=341 · 82% consumer	not reported in cached trials
Child neglect	29	137.3 92.8–203.2ROR 137.5 · χ² 3,268 / p <1e-300	110.2 EB05 80.4 · IC025 +4.7 3/3 methods agree	Not in label — unassessed	serious n=12 · 100% consumer	not reported in cached trials
Selective abortion	24	137.0 89.1–210.7ROR 137.1 · χ² 2,679 / p <1e-300	108.3 EB05 76.6 · IC025 +4.4 3/3 methods agree	Not in label — unassessed	serious n=23 · ♀ 100% (drug 50%)	not reported in cached trials
Substance abuse	1,008	123.4 115.6–131.6ROR 128.7 · χ² 106,964 / p <1e-300	107.8 EB05 102.4 · IC025 +6.6 3/3 methods agree	Reporting / coding artifact	serious PRR 60.9 · 82% consumer	not reported in cached trials
Oral administration complication	106	111.3 90.9–136.2ROR 111.8 · χ² 10,161 / p <1e-300	97.0 EB05 82.4 · IC025 +5.8 3/3 methods agree	Reporting / coding artifact	serious n=20	not reported in cached trials
Drug screen negative	174	95.6 81.8–111.8ROR 96.3 · χ² 14,582 / p <1e-300	85.4 EB05 75.3 · IC025 +5.9 3/3 methods agree	Reporting / coding artifact	serious n=18	not reported in cached trials
Product dosage form issue	44	87.8 64.4–119.7ROR 87.9 · χ² 3,347 / p <1e-300	77.2 EB05 59.9 · IC025 +4.9 3/3 methods agree	Reporting / coding artifact	serious n=27 · ♀ 79% (drug 50%)	not reported in cached trials
Tremor neonatal	37	78.3 56.0–109.7ROR 78.5 · χ² 2,519 / p <1e-300	69.4 EB05 52.6 · IC025 +4.7 3/3 methods agree	Labeled (related wording) related wording	serious n=37 · ♀ 29% (drug 50%)	not reported in cached trials
Diarrhoea neonatal	10	73.7 38.6–140.5ROR 73.7 · χ² 595 / p 1e-131	60.5 EB05 35.1 · IC025 +2.9 3/3 methods agree	Labeled (related wording) related wording	serious n=10	not reported in cached trials
Vision abnormal neonatal	30	66.6 46.0–96.6ROR 66.7 · χ² 1,740 / p <1e-300	59.7 EB05 43.8 · IC025 +4.3 3/3 methods agree	Labeled (related wording) related wording	serious n=30 · 100% consumer	not reported in cached trials
Drug withdrawal syndrome neonatal	913	56.8 53.2–60.7ROR 59.0 · χ² 46,945 / p <1e-300	53.3 EB05 50.5 · IC025 +5.6 3/3 methods agree	Labeled (related wording) related wording	serious PRR 48.4	not reported in cached trials
Dental caries	660	55.5 51.4–60.0ROR 57.1 · χ² 33,164 / p <1e-300	52.1 EB05 48.9 · IC025 +5.5 3/3 methods agree	Not in label — unassessed	serious PRR 40.3 · 84% consumer	not reported in cached trials
Neonatal hypoacusis	13	51.2 29.2–89.5ROR 51.2 · χ² 557 / p 2e-123	45.4 EB05 28.2 · IC025 +3.2 3/3 methods agree	Not in label — unassessed	serious n=13	not reported in cached trials
Poor feeding infant	57	49.2 37.7–64.3ROR 49.3 · χ² 2,502 / p <1e-300	45.9 EB05 36.8 · IC025 +4.6 3/3 methods agree	Not in label — unassessed	serious n=57	not reported in cached trials
Crime	14	48.3 28.2–82.7ROR 48.3 · χ² 570 / p 3e-126	43.3 EB05 27.4 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	–	not reported in cached trials
Weight decrease neonatal	10	47.1 24.9–89.0ROR 47.1 · χ² 385 / p 5e-86	41.4 EB05 24.0 · IC025 +2.8 3/3 methods agree	Labeled (related wording) related wording	serious n=10	not reported in cached trials
Detoxification	17	44.8 27.5–72.9ROR 44.8 · χ² 651 / p 7e-144	40.8 EB05 27.0 · IC025 +3.5 3/3 methods agree	Not in label — unassessed	serious n=17	NCT00723697: 2/1,305 (0.2%) on Buprenorphine and Naloxone (serious AE)
Learning disability	259	44.1 38.9–49.9ROR 44.5 · χ² 10,331 / p <1e-300	41.8 EB05 37.7 · IC025 +5.1 3/3 methods agree	Not in label — unassessed	serious n=259 · 98% consumer	not reported in cached trials
Alcohol abuse	122	41.4 34.6–49.7ROR 41.6 · χ² 4,554 / p <1e-300	39.3 EB05 33.8 · IC025 +4.8 3/3 methods agree	Reporting / coding artifact	serious n=68	not reported in cached trials
Jaundice neonatal	80	38.5 30.7–48.1ROR 38.6 · χ² 2,758 / p <1e-300	36.6 EB05 30.3 · IC025 +4.5 3/3 methods agree	Labeled (related wording) related wording	serious n=78	not reported in cached trials
Theft	26	35.3 23.8–52.2ROR 35.3 · χ² 799 / p 4e-176	33.2 EB05 23.8 · IC025 +3.7 3/3 methods agree	Not in label — unassessed	serious n=13 · 100% consumer	not reported in cached trials
Drug withdrawal syndrome	3,345	34.2 33.2–35.4ROR 39.6 · χ² 104,219 / p <1e-300	33.0 EB05 32.0 · IC025 +5.0 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 24.9 · 77% consumer	not reported in cached trials
Product preparation error	775	34.0 31.6–36.5ROR 35.1 · χ² 23,848 / p <1e-300	32.7 EB05 30.8 · IC025 +4.9 3/3 methods agree	Reporting / coding artifact	serious n=181 · 78% consumer	not reported in cached trials
Exposure during breast feeding	125	33.7 28.2–40.3ROR 33.9 · χ² 3,792 / p <1e-300	32.4 EB05 27.9 · IC025 +4.6 3/3 methods agree	Not in label — unassessed	serious n=114	not reported in cached trials
Tongue blistering	83	33.6 27.0–41.8ROR 33.7 · χ² 2,495 / p <1e-300	32.2 EB05 26.8 · IC025 +4.4 3/3 methods agree	Not in label — unassessed	serious n=29	not reported in cached trials
Drug diversion	195	30.8 26.7–35.5ROR 31.0 · χ² 5,401 / p <1e-300	29.7 EB05 26.4 · IC025 +4.6 3/3 methods agree	Reporting / coding artifact	serious n=87 · 77% consumer	not reported in cached trials
Exposure via body fluid	26	29.6 20.1–43.8ROR 29.7 · χ² 668 / p 1e-147	28.2 EB05 20.2 · IC025 +3.6 3/3 methods agree	Reporting / coding artifact	88% consumer	not reported in cached trials
Exposure to allergen	10	29.0 15.5–54.5ROR 29.0 · χ² 235 / p 2e-53	26.7 EB05 15.3 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious n=10	not reported in cached trials
Piloerection	34	28.1 20.0–39.6ROR 28.2 · χ² 835 / p 6e-184	26.9 EB05 20.1 · IC025 +3.7 3/3 methods agree	Not in label — unassessed	serious n=12	not reported in cached trials
Developmental delay	280	27.7 24.6–31.2ROR 28.1 · χ² 6,968 / p <1e-300	26.9 EB05 24.3 · IC025 +4.5 3/3 methods agree	Not in label — unassessed	serious PRR 24.7 · 99% consumer	not reported in cached trials
Euphoric mood	302	26.4 23.5–29.6ROR 26.7 · χ² 7,133 / p <1e-300	25.6 EB05 23.3 · IC025 +4.4 3/3 methods agree	Labeled adverse reaction exact term	serious n=121 · 72% consumer	not reported in cached trials
Victim of sexual abuse	14	24.3 14.3–41.3ROR 24.3 · χ² 282 / p 2e-63	22.9 EB05 14.3 · IC025 +2.8 3/3 methods agree	Reporting / coding artifact	serious n=12	not reported in cached trials
Teeth brittle	28	23.8 16.4–34.7ROR 23.8 · χ² 574 / p 4e-127	22.9 EB05 16.6 · IC025 +3.4 3/3 methods agree	Not in label — unassessed	serious n=17 · 100% consumer	not reported in cached trials
Drug dependence	4,302	23.7 23.1–24.4ROR 28.7 · χ² 91,843 / p <1e-300	23.1 EB05 22.5 · IC025 +4.5 3/3 methods agree	Reporting / coding artifact	serious PRR 19.1 · 85% consumer	NCT00723697: 1/1,305 (0.1%) on Buprenorphine and Naloxone (serious AE)
Sudden infant death syndrome	13	23.4 13.5–40.7ROR 23.4 · χ² 250 / p 1e-56	22.1 EB05 13.5 · IC025 +2.7 3/3 methods agree	Not in label — unassessed	serious n=13	not reported in cached trials
Exposure via father	33	22.4 15.8–31.6ROR 22.4 · χ² 636 / p 2e-140	21.6 EB05 16.1 · IC025 +3.5 3/3 methods agree	Reporting / coding artifact	serious n=18 · 77% consumer	not reported in cached trials

Trial evidence (ClinicalTrials.gov)

✓ Trial adverse-event data found on ClinicalTrials.gov

Largest completed trials with posted results that list Buprenorphine and Naloxone as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (3 of 40 signal terms matched).

NCT00723697 — Observational Study of Misuse of High Dose Buprenorphine (Subutex® or Generic) in Opiate-Addicted Patients in (N=1307, phase n/a; 25 AE terms posted; arms: Patients)
NCT00315341 — Starting Treatment With Agonist Replacement Therapies (START) (N=1269, PHASE4; 28 AE terms posted; arms: Buprenorphine/Nx; Methadone)

Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.

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 dependence	4,302	23.7 23.1–24.4ROR 28.7 · χ² 91,843 / p <1e-300	23.1 EB05 22.5 · IC025 +4.5 3/3 methods agree	Reporting / coding artifact	serious PRR 19.1 · 85% consumer	NCT00723697: 1/1,305 (0.1%) on Buprenorphine and Naloxone (serious AE)
Drug withdrawal syndrome	3,345	34.2 33.2–35.4ROR 39.6 · χ² 104,219 / p <1e-300	33.0 EB05 32.0 · IC025 +5.0 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 24.9 · 77% consumer	not reported in cached trials
Pain	2,563	3.7 3.5–3.8ROR 4.0 · χ² 5,064 / p <1e-300	3.6 EB05 3.5 · IC025 +1.8 3/3 methods agree	Likely indication confounding term in indications; also in warnings	serious PRR 4.1 · 78% consumer	NCT00315341: 50/727 (6.9%) on Buprenorphine and Naloxone
Off label use (used outside approved label)	2,075	2.1 2.0–2.2ROR 2.2 · χ² 1,232 / p 4e-270	2.1 EB05 2.0 · IC025 +1.0 3/3 methods agree	Reporting / coding artifact	serious PRR 0.9 · 72% consumer	not reported in cached trials
Overdose	1,864	7.6 7.3–7.9ROR 8.1 · χ² 10,659 / p <1e-300	7.5 EB05 7.2 · IC025 +2.8 3/3 methods agree	Reporting / coding artifact	serious PRR 8.5	not reported in cached trials
Nausea	1,649	1.8 1.7–1.9ROR 1.9 · χ² 642 / p 7e-142	1.8 EB05 1.8 · IC025 +0.8	Labeled adverse reaction exact term	serious PRR 1.8	not reported in cached trials
Emotional distress	1,484	10.8 10.3–11.3ROR 11.4 · χ² 13,099 / p <1e-300	10.7 EB05 10.2 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious PRR 9.9 · 92% consumer	not reported in cached trials
Anxiety	1,361	4.2 4.0–4.4ROR 4.4 · χ² 3,327 / p <1e-300	4.2 EB05 4.0 · IC025 +2.0 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 3.7 · 79% consumer	not reported in cached trials
Vomiting	1,344	2.5 2.4–2.6ROR 2.6 · χ² 1,244 / p 7e-273	2.5 EB05 2.4 · IC025 +1.2 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 2.1	NCT00315341: 28/727 (3.9%) on Buprenorphine and Naloxone
Headache	1,122	1.6 1.5–1.7ROR 1.6 · χ² 237 / p 1e-53	1.6 EB05 1.5 · IC025 +0.5	Labeled adverse reaction exact term	serious PRR 1.7	NCT00315341: 102/727 (14.0%) on Buprenorphine and Naloxone
Drug abuse	1,111	11.8 11.1–12.5ROR 12.3 · χ² 10,819 / p <1e-300	11.6 EB05 11.0 · IC025 +3.4 3/3 methods agree	Reporting / coding artifact	serious PRR 8.4	not reported in cached trials
Insomnia (trouble sleeping)	1,080	3.6 3.3–3.8ROR 3.7 · χ² 1,993 / p <1e-300	3.5 EB05 3.4 · IC025 +1.7 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 3.6 · 85% consumer	NCT00723697: 1/1,305 (0.1%) on Buprenorphine and Naloxone (serious AE)
Foetal exposure during pregnancy	1,053	11.5 10.8–12.2ROR 11.9 · χ² 9,959 / p <1e-300	11.3 EB05 10.8 · IC025 +3.4 3/3 methods agree	Reporting / coding artifact	serious PRR 10.3	not reported in cached trials
Depression	1,034	4.0 3.7–4.2ROR 4.1 · χ² 2,309 / p <1e-300	3.9 EB05 3.8 · IC025 +1.9 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 3.9 · 83% consumer	NCT00723697: 1/1,305 (0.1%) on Buprenorphine and Naloxone (serious AE)
Intentional underdose	1,027	143.6 134.5–153.2ROR 149.9 · χ² 124,548 / p <1e-300	122.9 EB05 116.7 · IC025 +6.8 3/3 methods agree	Not in label — unassessed	serious n=341 · 82% consumer	not reported in cached trials

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.

Drug detoxification — n=258, PRR 357.5 (also seen in trial arm)
Tooth erosion — n=295, PRR 306.3
Therapy naive — n=20, PRR 175.9
Intentional underdose — n=1,027, PRR 143.6
Child neglect — n=29, PRR 137.3
Selective abortion — n=24, PRR 137.0
Dental caries — n=660, PRR 55.5
Poor feeding infant — n=57, PRR 49.2
Learning disability — n=259, PRR 44.1
Theft — n=26, PRR 35.3

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 Buprenorphine and Naloxone?

In FDA FAERS, the most frequently co-reported reaction terms for Buprenorphine and Naloxone are drug withdrawal syndrome, pain, nausea, emotional distress, anxiety, vomiting. 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 Buprenorphine and Naloxone have an FDA boxed warning?

Yes. The current FDA label carries a boxed warning: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF BUPRENORPHINE TRANSDERMAL SYSTEM Addiction, Abuse, and Misuse Because the use of buprenorphine transdermal system exposes patients and other users to the risks of opioid.

Do FAERS signals prove that Buprenorphine and Naloxone 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 186e3be6-8bc0-4bb9-96f5-429d53632f45, effective 20260428; matched on openfda.generic_name.exact:"BUPRENORPHINE")
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, 1,130 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
ClinicalTrials.gov API v2 (query BUPRENORPHINE, results-bearing studies sorted by enrollment)

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.