Diphenhydramine HCL side effects: what 11,074 FDA adverse event reports show

Diphenhydramine Hcl · Nightime Sleep Aid · 1,124 reaction terms · 50,118 drug–reaction co-reports · data 2026-09-14

Drug class

Not stated in label

Brand names

Nightime Sleep Aid

openFDA label

Who reports

11,074 reports · 79% serious · 3,061 with death outcome · 61% female

openFDA FAERS counts, all years, deduplication not applied

Used for

For relief of occasional sleeplessness.

FDA label, Indications and Usage

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 12Outcome field, not a reaction 2No label text to screen 25

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.
Outcome field, not a reaction Death is a report outcome, not a reaction term. It is dominated by the underlying illness; see the seriousness profile and the boxed warning instead.
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.
No label text to screen No validated FDA label was retrievable for this product, so the screen could not run. Disproportionality only.

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. 1,084 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
Multiple drug overdose accidental	20	85.3 54.5–133.4ROR 85.4 · χ² 1,513 / p <1e-300	75.9 EB05 51.9 · IC025 +4.0 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=20 · ♀ 40% (drug 61%)	no trial arm names this drug
Multiple drug overdose	123	47.4 39.7–56.6ROR 47.9 · χ² 5,404 / p <1e-300	45.9 EB05 39.5 · IC025 +5.0 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=123 · 100% clinician	no trial arm names this drug
Blood pressure systolic abnormal	53	41.2 31.4–54.0ROR 41.3 · χ² 1,993 / p <1e-300	39.8 EB05 31.6 · IC025 +4.4 3/3 methods agree	Lab value / disease marker	serious n=53 · 92% clinician	no trial arm names this drug
Blood pressure diastolic abnormal	52	39.1 29.7–51.4ROR 39.3 · χ² 1,853 / p <1e-300	37.8 EB05 29.9 · IC025 +4.4 3/3 methods agree	Lab value / disease marker	serious n=50	no trial arm names this drug
Visceral congestion	10	39.1 20.9–73.1ROR 39.1 · χ² 327 / p 2e-73	35.9 EB05 20.8 · IC025 +2.7 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=10	no trial arm names this drug
Drug toxicity	279	39.0 34.7–43.9ROR 40.0 · χ² 10,092 / p <1e-300	38.1 EB05 34.5 · IC025 +5.0 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious PRR 28.6 · 95% clinician	no trial arm names this drug
Multiple drug overdose intentional	59	34.9 27.0–45.1ROR 35.0 · χ² 1,872 / p <1e-300	33.9 EB05 27.2 · IC025 +4.3 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=59 · 100% clinician	no trial arm names this drug
Granulomatosis with polyangiitis	18	29.1 18.2–46.3ROR 29.1 · χ² 453 / p 9e-101	27.9 EB05 18.6 · IC025 +3.2 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=18	no trial arm names this drug
Intentional misuse	26	25.8 17.5–37.9ROR 25.8 · χ² 586 / p 9e-130	25.0 EB05 17.9 · IC025 +3.5 3/3 methods agree	Reporting / coding artifact	serious n=26 · ♀ 35% (drug 61%)	no trial arm names this drug
Anticholinergic syndrome	19	22.8 14.5–35.9ROR 22.9 · χ² 371 / p 7e-83	22.1 EB05 14.9 · IC025 +3.1 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=18	no trial arm names this drug
Accidental death	21	21.7 14.1–33.3ROR 21.7 · χ² 390 / p 5e-87	21.1 EB05 14.4 · IC025 +3.1 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=22	no trial arm names this drug
Respiratory arrest	299	20.6 18.4–23.0ROR 21.1 · χ² 5,493 / p <1e-300	20.3 EB05 18.5 · IC025 +4.1 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious PRR 14.8 · 99% clinician	no trial arm names this drug
Blood pressure diastolic decreased	77	19.9 15.9–24.8ROR 20.0 · χ² 1,346 / p 5e-295	19.6 EB05 16.2 · IC025 +3.8 3/3 methods agree	Lab value / disease marker	serious PRR 15.1	no trial arm names this drug
Anaphylactoid reaction	39	18.2 13.3–24.9ROR 18.2 · χ² 611 / p 4e-135	17.9 EB05 13.6 · IC025 +3.4 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=38 · 100% clinician	no trial arm names this drug
Completed suicide (death by suicide)	797	18.1 16.9–19.4ROR 19.4 · χ² 12,785 / p <1e-300	17.9 EB05 16.9 · IC025 +4.0 3/3 methods agree	Outcome field, not a reaction	serious PRR 13.0 · 98% clinician	no trial arm names this drug
Respiratory rate increased	73	15.6 12.4–19.7ROR 15.7 · χ² 978 / p 4e-215	15.4 EB05 12.6 · IC025 +3.4 3/3 methods agree	Lab value / disease marker	serious PRR 12.6 · 94% clinician	no trial arm names this drug
Exposure to toxic agent	25	14.8 10.0–21.9ROR 14.8 · χ² 306 / p 1e-68	14.3 EB05 9.9 · IC025 +2.9 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=25 · 100% clinician	no trial arm names this drug
Poisoning	95	14.4 11.7–17.6ROR 14.5 · χ² 1,159 / p 3e-254	14.2 EB05 11.9 · IC025 +3.4 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious PRR 10.5 · 100% clinician	no trial arm names this drug
Infusion related reaction (reaction during infusion)	496	14.3 13.1–15.6ROR 14.9 · χ² 6,104 / p <1e-300	14.2 EB05 13.2 · IC025 +3.7 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious PRR 12.5	no trial arm names this drug
Serum sickness	20	13.7 8.8–21.3ROR 13.7 · χ² 222 / p 2e-50	12.9 EB05 8.4 · IC025 +2.6 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=20	no trial arm names this drug
Mucous membrane disorder	10	13.7 7.4–25.5ROR 13.7 · χ² 105 / p 7e-25	11.7 EB05 5.8 · IC025 +2.0 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=10	no trial arm names this drug
Pupil fixed	12	13.1 7.4–23.1ROR 13.1 · χ² 121 / p 1e-28	11.5 EB05 6.2 · IC025 +2.2 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=12	no trial arm names this drug
Cardio-respiratory arrest	287	13.0 11.6–14.6ROR 13.3 · χ² 3,150 / p <1e-300	12.9 EB05 11.7 · IC025 +3.5 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious PRR 9.4 · 99% clinician	no trial arm names this drug
Flat affect	15	12.6 7.6–20.9ROR 12.6 · χ² 147 / p 4e-34	11.3 EB05 6.6 · IC025 +2.3 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=15	no trial arm names this drug
Blood pressure systolic increased	127	12.3 10.4–14.7ROR 12.5 · χ² 1,306 / p 4e-286	12.2 EB05 10.5 · IC025 +3.3 3/3 methods agree	Lab value / disease marker	serious PRR 9.5	no trial arm names this drug
Brain death	19	11.7 7.4–18.3ROR 11.7 · χ² 174 / p 6e-40	10.6 EB05 6.7 · IC025 +2.4 3/3 methods agree	Outcome field, not a reaction	serious n=19	no trial arm names this drug
Blood pressure diastolic increased	27	11.1 7.6–16.2ROR 11.1 · χ² 236 / p 1e-53	10.3 EB05 7.2 · IC025 +2.6 3/3 methods agree	Lab value / disease marker	serious n=26 · 93% clinician	no trial arm names this drug
Blood ph decreased	10	11.1 5.9–20.6ROR 11.1 · χ² 81 / p 1e-19	8.9 EB05 4.6 · IC025 +1.8 3/3 methods agree	Lab value / disease marker	serious n=10	no trial arm names this drug
Blood bicarbonate decreased	11	11.0 6.1–19.8ROR 11.0 · χ² 89 / p 2e-21	9.0 EB05 4.9 · IC025 +1.9 3/3 methods agree	Lab value / disease marker	serious n=11	no trial arm names this drug
Blood pressure fluctuation	135	10.7 9.0–12.6ROR 10.8 · χ² 1,169 / p 2e-256	10.5 EB05 9.1 · IC025 +3.1 3/3 methods agree	Lab value / disease marker	serious PRR 9.5	no trial arm names this drug
Mucosal dryness	11	10.5 5.8–18.9ROR 10.5 · χ² 85 / p 2e-20	8.5 EB05 4.7 · IC025 +1.9 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=11	no trial arm names this drug
Pupillary reflex impaired	10	10.4 5.6–19.4ROR 10.5 · χ² 76 / p 2e-18	8.3 EB05 4.4 · IC025 +1.8 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=10	no trial arm names this drug
Body temperature decreased	54	10.3 7.9–13.5ROR 10.4 · χ² 444 / p 6e-99	10.0 EB05 7.8 · IC025 +2.8 3/3 methods agree	Lab value / disease marker	serious PRR 8.1	no trial arm names this drug
Excoriation	14	10.3 6.1–17.5ROR 10.4 · χ² 108 / p 1e-25	8.8 EB05 5.2 · IC025 +2.1 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=14	no trial arm names this drug
Electrocardiogram qrs complex prolonged	27	10.0 6.9–14.6ROR 10.1 · χ² 210 / p 8e-48	9.2 EB05 6.4 · IC025 +2.5 3/3 methods agree	Lab value / disease marker	serious n=27 · 100% clinician	no trial arm names this drug
Oxygen saturation decreased	283	9.6 8.6–10.8ROR 9.9 · χ² 2,179 / p <1e-300	9.5 EB05 8.6 · IC025 +3.0 3/3 methods agree	Lab value / disease marker	serious PRR 7.6	no trial arm names this drug
Drug abuser	30	9.2 6.4–13.1ROR 9.2 · χ² 209 / p 1e-47	8.4 EB05 6.0 · IC025 +2.4 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=31 · 100% clinician	no trial arm names this drug
Cardiac arrest (heart stopping)	370	8.5 7.7–9.4ROR 8.7 · χ² 2,435 / p <1e-300	8.4 EB05 7.7 · IC025 +2.9 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious PRR 6.1 · 97% clinician	no trial arm names this drug
Computerised tomogram abnormal	10	8.3 4.5–15.5ROR 8.3 · χ² 57 / p 2e-14	6.5 EB05 3.6 · IC025 +1.5 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=9	no trial arm names this drug
Sinus tachycardia	62	8.3 6.5–10.7ROR 8.4 · χ² 390 / p 4e-87	7.9 EB05 6.4 · IC025 +2.5 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious PRR 6.0	no trial arm names this drug

Trial evidence (ClinicalTrials.gov)

ClinicalTrials.gov returned results-bearing trials mentioning Diphenhydramine only as a background or rescue medication (NCT00153101, NCT02625181); 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
Completed suicide (death by suicide)	797	18.1 16.9–19.4ROR 19.4 · χ² 12,785 / p <1e-300	17.9 EB05 16.9 · IC025 +4.0 3/3 methods agree	Outcome field, not a reaction	serious PRR 13.0 · 98% clinician	no trial arm names this drug
Death	684	1.5 1.4–1.6ROR 1.5 · χ² 120 / p 3e-28	1.5 EB05 1.4 · IC025 +0.5	Outcome field, not a reaction	serious PRR 1.1	no trial arm names this drug
Fatigue (tiredness)	651	1.6 1.5–1.7ROR 1.6 · χ² 146 / p 6e-34	1.6 EB05 1.5 · IC025 +0.5	No label text to screen label has no adverse-reaction text	serious PRR 1.7	no trial arm names this drug
Nausea	629	1.5 1.4–1.6ROR 1.5 · χ² 112 / p 2e-26	1.5 EB05 1.4 · IC025 +0.5	No label text to screen label has no adverse-reaction text	serious PRR 1.7	no trial arm names this drug
Pain	565	1.7 1.6–1.9ROR 1.8 · χ² 182 / p 9e-42	1.7 EB05 1.6 · IC025 +0.7	No label text to screen label has no adverse-reaction text	serious PRR 1.7	no trial arm names this drug
Dyspnoea (shortness of breath)	547	1.8 1.7–2.0ROR 1.9 · χ² 211 / p 3e-48	1.8 EB05 1.7 · IC025 +0.7	No label text to screen label has no adverse-reaction text	serious PRR 1.6	no trial arm names this drug
Diarrhoea (diarrhea)	532	1.6 1.4–1.7ROR 1.6 · χ² 112 / p 2e-26	1.6 EB05 1.5 · IC025 +0.5	No label text to screen label has no adverse-reaction text	serious PRR 1.5	no trial arm names this drug
Headache	508	1.5 1.4–1.7ROR 1.6 · χ² 97 / p 3e-23	1.5 EB05 1.4 · IC025 +0.5	No label text to screen label has no adverse-reaction text	serious PRR 1.8	no trial arm names this drug
Drug ineffective (drug did not work)	497	0.7 0.7–0.8ROR 0.7 · χ² 60 / p 4e-15	0.7 EB05 0.7 · IC025 -0.6 PRR-only: not supported by EBGM or IC	Reporting / coding artifact	serious PRR 0.9	no trial arm names this drug
Infusion related reaction (reaction during infusion)	496	14.3 13.1–15.6ROR 14.9 · χ² 6,104 / p <1e-300	14.2 EB05 13.2 · IC025 +3.7 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious PRR 12.5	no trial arm names this drug
Arthralgia (joint pain)	473	2.2 2.0–2.4ROR 2.2 · χ² 300 / p 2e-67	2.2 EB05 2.0 · IC025 +1.0 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious PRR 2.5	no trial arm names this drug
Rash	430	1.9 1.7–2.1ROR 1.9 · χ² 179 / p 3e-41	1.9 EB05 1.7 · IC025 +0.7	No label text to screen label has no adverse-reaction text	serious PRR 2.0	no trial arm names this drug
Vomiting	429	1.7 1.6–1.9ROR 1.8 · χ² 135 / p 1e-31	1.7 EB05 1.6 · IC025 +0.6	No label text to screen label has no adverse-reaction text	serious PRR 1.6	no trial arm names this drug
Pyrexia (fever)	410	2.2 2.0–2.5ROR 2.3 · χ² 286 / p 2e-64	2.2 EB05 2.1 · IC025 +1.0 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious PRR 1.9	no trial arm names this drug
Toxicity to various agents	396	4.5 4.1–4.9ROR 4.6 · χ² 1,071 / p 3e-235	4.4 EB05 4.1 · IC025 +2.0 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious PRR 3.3 · 92% clinician	no trial arm names this drug

Unlabeled candidate signals

Every screened signal with n ≥ 20 was either labeled, an indication term, or an artifact pattern — no unlabeled candidate stood out in the top signals.

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 Diphenhydramine?

In FDA FAERS, the most frequently co-reported reaction terms for Diphenhydramine are fatigue, nausea, pain, dyspnoea, diarrhoea, headache. 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 Diphenhydramine have an FDA boxed warning?

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

Do FAERS signals prove that Diphenhydramine 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 9c44e54f-d8bc-4451-8382-40d2e8e03b42, effective 20180521; matched on openfda.generic_name.exact:"DIPHENHYDRAMINE")
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, 1,124 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 DIPHENHYDRAMINE, 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.