Drug · FAERS side-effect profile with label screen
Diphenoxylate and Atropine side effects: what 13,612 FDA adverse event reports show
Drug class
Not stated in label
Label matched
Diphenoxylate Hydrochloride And Atropine Sulfate (Diphenoxylate Hydrochloride And Atropine 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
13,612 reports · 66% serious · 1,339 with death outcome · 64% female
openFDA FAERS counts, all years, deduplication not applied
Used for
Diphenoxylate hydrochloride and atropine sulfate tablets are indicated as adjunctive therapy in the management of diarrhea in patients 13 years of age and older.
FDA label, Indications and Usage
What it is
DESCRIPTION Each diphenoxylate hydrochloride and atropine sulfate tablet, USP contains: 2.5 mg of diphenoxylate hydrochloride, USP (equivalent to 2.3 mg of diphenoxylate) and 0.025 mg of atrop.
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 2Lab value / disease marker 8Not in label — unassessed 30
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. 1,118 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 |
|---|---|---|---|---|---|---|
| Vaginal flatulence | 77 | 519.6 401.4–672.7ROR 522.6 · χ² 29,310 / p <1e-300 | 353.3 EB05 291.9 · IC025 +6.4 3/3 methods agree | Not in label — unassessed | serious n=77 · ♀ 100% (drug 64%) | no trial arm names this drug |
| Presbyacusis | 60 | 368.8 278.3–488.8ROR 370.5 · χ² 17,414 / p <1e-300 | 271.3 EB05 218.4 · IC025 +6.0 3/3 methods agree | Not in label — unassessed | serious n=60 · ♀ 100% (drug 64%) | no trial arm names this drug |
| Gastrointestinal stoma output abnormal | 16 | 192.8 114.6–324.3ROR 193.0 · χ² 2,541 / p <1e-300 | 142.5 EB05 93.0 · IC025 +4.0 3/3 methods agree | Lab value / disease marker | serious n=16 | no trial arm names this drug |
| Pleural thickening | 56 | 137.8 104.9–181.1ROR 138.4 · χ² 6,848 / p <1e-300 | 121.3 EB05 96.9 · IC025 +5.5 3/3 methods agree | Not in label — unassessed | serious n=56 · ♀ 100% (drug 64%) | no trial arm names this drug |
| Pleural fibrosis | 70 | 112.2 88.1–143.0ROR 112.8 · χ² 7,083 / p <1e-300 | 101.7 EB05 83.3 · IC025 +5.5 3/3 methods agree | Not in label — unassessed | serious n=70 · ♀ 92% (drug 64%) | no trial arm names this drug |
| Blood magnesium increased | 57 | 103.7 79.3–135.5ROR 104.1 · χ² 5,329 / p <1e-300 | 94.1 EB05 75.3 · IC025 +5.3 3/3 methods agree | Lab value / disease marker | serious n=57 · ♀ 100% (drug 64%) | no trial arm names this drug |
| Gastrointestinal stoma output increased | 26 | 91.6 61.7–136.0ROR 91.8 · χ² 2,113 / p <1e-300 | 81.4 EB05 58.4 · IC025 +4.4 3/3 methods agree | Lab value / disease marker | serious n=25 | no trial arm names this drug |
| Female genital tract fistula | 88 | 82.9 67.0–102.7ROR 83.5 · χ² 6,678 / p <1e-300 | 77.4 EB05 64.8 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | serious n=88 · ♀ 100% (drug 64%) | no trial arm names this drug |
| Gastroenteritis radiation | 15 | 73.2 43.6–122.9ROR 73.3 · χ² 952 / p 3e-209 | 64.4 EB05 41.5 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=15 | no trial arm names this drug |
| Bone cyst | 41 | 70.2 51.3–95.9ROR 70.4 · χ² 2,607 / p <1e-300 | 65.2 EB05 50.1 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious n=41 · ♀ 100% (drug 64%) | no trial arm names this drug |
| Short-bowel syndrome | 23 | 56.3 37.2–85.4ROR 56.4 · χ² 1,152 / p 6e-253 | 52.1 EB05 36.6 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | serious n=22 | no trial arm names this drug |
| Chronic sinusitis | 124 | 52.7 44.1–63.0ROR 53.2 · χ² 6,027 / p <1e-300 | 50.6 EB05 43.5 · IC025 +5.1 3/3 methods agree | Not in label — unassessed | serious n=122 · ♀ 100% (drug 64%) | no trial arm names this drug |
| Stoma complication | 33 | 51.4 36.4–72.7ROR 51.6 · χ² 1,530 / p <1e-300 | 48.5 EB05 36.1 · IC025 +4.3 3/3 methods agree | Reporting / coding artifact | serious n=31 | no trial arm names this drug |
| Radiculopathy | 83 | 50.0 40.2–62.2ROR 50.3 · χ² 3,813 / p <1e-300 | 47.9 EB05 39.9 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious n=82 · ♀ 100% (drug 64%) | no trial arm names this drug |
| Proctitis | 88 | 49.9 40.3–61.6ROR 50.2 · χ² 4,033 / p <1e-300 | 47.8 EB05 40.0 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious n=87 · ♀ 93% (drug 64%) | no trial arm names this drug |
| Osteosclerosis | 49 | 49.3 37.1–65.5ROR 49.5 · χ² 2,201 / p <1e-300 | 47.0 EB05 37.0 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious n=49 · ♀ 89% (drug 64%) | no trial arm names this drug |
| Bulimia nervosa | 11 | 39.3 21.6–71.5ROR 39.3 · χ² 364 / p 2e-81 | 36.1 EB05 21.5 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=11 | no trial arm names this drug |
| Pouchitis | 21 | 38.4 24.9–59.2ROR 38.5 · χ² 710 / p 8e-157 | 36.4 EB05 25.1 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=18 · ♀ 43% (drug 64%) | no trial arm names this drug |
| Faecal volume decreased | 11 | 35.8 19.7–65.2ROR 35.9 · χ² 331 / p 3e-74 | 33.2 EB05 19.7 · IC025 +2.8 3/3 methods agree | Lab value / disease marker | serious n=9 | no trial arm names this drug |
| Gastrointestinal stoma complication | 33 | 33.2 23.5–46.9ROR 33.3 · χ² 978 / p 5e-215 | 32.0 EB05 23.8 · IC025 +3.9 3/3 methods agree | Reporting / coding artifact | serious n=31 | no trial arm names this drug |
| Deafness neurosensory | 64 | 30.6 23.9–39.2ROR 30.8 · χ² 1,770 / p <1e-300 | 29.8 EB05 24.2 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | serious n=64 · ♀ 100% (drug 64%) | no trial arm names this drug |
| Rectal fissure | 12 | 29.5 16.7–52.3ROR 29.6 · χ² 297 / p 7e-67 | 27.8 EB05 16.9 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=11 | no trial arm names this drug |
| Macular degeneration | 217 | 28.5 25.0–32.6ROR 29.0 · χ² 5,637 / p <1e-300 | 28.0 EB05 25.0 · IC025 +4.5 3/3 methods agree | Not in label — unassessed | serious PRR 26.5 · ♀ 100% (drug 64%) | no trial arm names this drug |
| Epigastric discomfort | 68 | 27.1 21.4–34.5ROR 27.3 · χ² 1,657 / p <1e-300 | 26.5 EB05 21.6 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=66 · ♀ 100% (drug 64%) | no trial arm names this drug |
| Perirectal abscess | 13 | 18.1 10.5–31.3ROR 18.1 · χ² 191 / p 8e-44 | 17.1 EB05 10.0 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious n=11 | no trial arm names this drug |
| Chronic kidney disease-mineral and bone disorder | 12 | 17.4 9.8–30.6ROR 17.4 · χ² 167 / p 2e-38 | 16.1 EB05 9.0 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious n=12 | no trial arm names this drug |
| Intestinal dilatation | 14 | 16.4 9.7–27.8ROR 16.5 · χ² 186 / p 1e-42 | 15.4 EB05 9.1 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious n=14 | no trial arm names this drug |
| Culture urine positive | 14 | 15.4 9.1–26.1ROR 15.4 · χ² 173 / p 1e-39 | 14.3 EB05 8.3 · IC025 +2.5 3/3 methods agree | Lab value / disease marker | serious n=14 | no trial arm names this drug |
| Blood magnesium decreased | 85 | 15.3 12.4–18.9ROR 15.4 · χ² 1,111 / p 6e-244 | 15.1 EB05 12.5 · IC025 +3.4 3/3 methods agree | Lab value / disease marker | serious PRR 13.5 | no trial arm names this drug |
| Small intestinal obstruction | 117 | 14.8 12.4–17.8ROR 14.9 · χ² 1,480 / p <1e-300 | 14.6 EB05 12.5 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious PRR 12.8 | no trial arm names this drug |
| Therapeutic reaction time decreased | 28 | 14.8 10.2–21.4ROR 14.8 · χ² 343 / p 8e-77 | 14.3 EB05 10.1 · IC025 +2.9 3/3 methods agree | Lab value / disease marker | serious n=26 | no trial arm names this drug |
| Paraesthesia oral | 134 | 14.5 12.2–17.2ROR 14.6 · χ² 1,654 / p <1e-300 | 14.3 EB05 12.4 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious PRR 20.9 · ♀ 94% (drug 64%) | no trial arm names this drug |
| Vascular device infection | 42 | 14.4 10.7–19.6ROR 14.5 · χ² 507 / p 1e-112 | 14.1 EB05 10.7 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=42 | no trial arm names this drug |
| Failure to thrive | 47 | 14.0 10.5–18.7ROR 14.0 · χ² 550 / p 8e-122 | 13.7 EB05 10.6 · IC025 +3.1 3/3 methods agree | Not in label — unassessed | serious n=47 | no trial arm names this drug |
| Blood electrolytes abnormal | 11 | 13.8 7.6–25.0ROR 13.8 · χ² 117 / p 1e-27 | 12.1 EB05 6.3 · IC025 +2.1 3/3 methods agree | Lab value / disease marker | serious n=10 | no trial arm names this drug |
| Hyperparathyroidism secondary | 22 | 13.5 8.9–20.5ROR 13.5 · χ² 240 / p 2e-54 | 12.8 EB05 8.5 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=22 | no trial arm names this drug |
| Incisional hernia | 12 | 13.4 7.6–23.7ROR 13.4 · χ² 125 / p 3e-29 | 11.8 EB05 6.4 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious n=11 | no trial arm names this drug |
| Nephrogenic anaemia | 40 | 13.3 9.7–18.1ROR 13.3 · χ² 438 / p 1e-97 | 12.9 EB05 9.7 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious n=40 | no trial arm names this drug |
| Frequent bowel movements | 229 | 13.2 11.6–15.0ROR 13.4 · χ² 2,553 / p <1e-300 | 13.1 EB05 11.7 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious PRR 14.3 | no trial arm names this drug |
| Rectal abscess | 14 | 12.9 7.6–21.8ROR 12.9 · χ² 141 / p 8e-33 | 11.5 EB05 6.6 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious n=11 | no trial arm names this drug |
Trial evidence (ClinicalTrials.gov)
ClinicalTrials.gov returned results-bearing trials mentioning Diphenoxylate and Atropine only as a background or rescue medication (NCT02858310, NCT03030417); no trial listing it as the tested intervention was cached, so no trial cross-check is shown.
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 |
|---|---|---|---|---|---|---|
| Diarrhoea (diarrhea) | 2,730 | 6.6 6.3–6.8ROR 8.0 · χ² 13,207 / p <1e-300 | 6.5 EB05 6.3 · IC025 +2.6 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 6.7 | no trial arm names this drug |
| Nausea | 1,620 | 3.2 3.0–3.3ROR 3.5 · χ² 2,487 / p <1e-300 | 3.2 EB05 3.0 · IC025 +1.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.8 | no trial arm names this drug |
| Fatigue (tiredness) | 1,475 | 2.9 2.8–3.1ROR 3.2 · χ² 1,938 / p <1e-300 | 2.9 EB05 2.8 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 3.2 | no trial arm names this drug |
| Drug ineffective (drug did not work) | 1,130 | 1.3 1.2–1.4ROR 1.4 · χ² 94 / p 2e-22 | 1.3 EB05 1.3 · IC025 +0.3 | Reporting / coding artifact | serious PRR 2.0 | no trial arm names this drug |
| Vomiting | 916 | 3.0 2.8–3.2ROR 3.2 · χ² 1,255 / p 4e-275 | 3.0 EB05 2.8 · IC025 +1.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.0 | no trial arm names this drug |
| Weight decreased (weight loss) | 885 | 4.9 4.6–5.2ROR 5.2 · χ² 2,768 / p <1e-300 | 4.9 EB05 4.6 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 5.2 | no trial arm names this drug |
| Pain | 782 | 2.0 1.8–2.1ROR 2.0 · χ² 376 / p 4e-84 | 2.0 EB05 1.8 · IC025 +0.8 | Not in label — unassessed | serious PRR 2.2 | no trial arm names this drug |
| Dehydration | 767 | 8.9 8.3–9.5ROR 9.4 · χ² 5,373 / p <1e-300 | 8.8 EB05 8.3 · IC025 +3.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 8.4 | no trial arm names this drug |
| Off label use (used outside approved label) | 752 | 1.3 1.2–1.4ROR 1.4 · χ² 65 / p 3e-16 | 1.3 EB05 1.3 · IC025 +0.3 | Reporting / coding artifact | serious PRR 1.6 | no trial arm names this drug |
| Abdominal pain | 744 | 4.9 4.6–5.3ROR 5.2 · χ² 2,353 / p <1e-300 | 4.9 EB05 4.6 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 4.7 | no trial arm names this drug |
| Asthenia (weakness) | 716 | 2.9 2.7–3.2ROR 3.0 · χ² 927 / p 8e-204 | 2.9 EB05 2.8 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 2.9 | no trial arm names this drug |
| Dyspnoea (shortness of breath) | 675 | 1.8 1.7–2.0ROR 1.9 · χ² 264 / p 1e-59 | 1.8 EB05 1.7 · IC025 +0.7 | Not in label — unassessed | serious PRR 1.8 | no trial arm names this drug |
| Headache | 671 | 1.7 1.5–1.8ROR 1.7 · χ² 177 / p 1e-40 | 1.6 EB05 1.5 · IC025 +0.6 | Labeled adverse reaction exact term | serious PRR 2.0 | no trial arm names this drug |
| Decreased appetite (loss of appetite) | 643 | 4.3 4.0–4.6ROR 4.4 · χ² 1,629 / p <1e-300 | 4.3 EB05 4.0 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 4.5 | no trial arm names this drug |
| Malaise (feeling unwell) | 594 | 2.1 1.9–2.3ROR 2.1 · χ² 340 / p 4e-76 | 2.1 EB05 1.9 · IC025 +0.9 | Labeled adverse reaction exact term | serious PRR 2.4 | no trial arm names this drug |
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.
- Vaginal flatulence — n=77, PRR 519.6
- Presbyacusis — n=60, PRR 368.8
- Pleural thickening — n=56, PRR 137.8
- Pleural fibrosis — n=70, PRR 112.2
- Female genital tract fistula — n=88, PRR 82.9
- Bone cyst — n=41, PRR 70.2
- Short-bowel syndrome — n=23, PRR 56.3
- Chronic sinusitis — n=124, PRR 52.7
- Radiculopathy — n=83, PRR 50.0
- Proctitis — n=88, PRR 49.9
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 Diphenoxylate and Atropine?
In FDA FAERS, the most frequently co-reported reaction terms for Diphenoxylate and Atropine are diarrhoea, nausea, fatigue, vomiting, weight decreased, pain. 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 Diphenoxylate and Atropine have an FDA boxed warning?
No. The FDA label retrieved for Diphenoxylate and Atropine has no boxed warning; see the label's Warnings and Precautions for the recognised risks.
Do FAERS signals prove that Diphenoxylate and Atropine 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 14bf7191-580f-76dc-e063-6294a90aed2a, effective 20240408; matched on
openfda.generic_name.exact:"DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE 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, 1,158 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
DIPHENOXYLATE, 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.