Diphenhydramine side effects: what 62,798 FDA adverse event reports show

Diphenhydramine · Nightime Sleep Aid · 1,213 reaction terms · 350,586 drug–reaction co-reports · data 2026-09-14

Drug class

Not stated in label

Brand names

Nightime Sleep Aid

openFDA label

Who reports

62,798 reports · 76% serious · 11,756 with death outcome · 64% 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 5No label text to screen 34

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.
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, for the 300 most-reported drugs, adjusted for age band), and flags pairs whose reports are unusually skewed by sex or come mostly from consumers. Each row also shows the PRR against the other drugs of the same FDA class, which removes most confounding by the condition being treated, and a calibrated p-value: on validation, known non-causes average an ROR of about 2, so significance is judged against that empirical null (✓ = p < 0.05 after calibration). 1,173 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
Vaginal flatulence	146	307.4 245.3–385.1ROR 308.1 · calibrated p 1e-11 ✓	156.0 EB05 135.9 · IC025 +6.4 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=146 · ♀ 100% (drug 64%)	no trial arm names this drug
Grip strength	77	166.4 126.5–218.8ROR 166.6 · calibrated p 4e-9 ✓	107.9 EB05 89.1 · IC025 +5.6 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=77 · ♀ 100% (drug 64%) · 100% clinician	no trial arm names this drug
Central nervous system lupus	55	113.6 83.6–154.3ROR 113.7 · calibrated p 8e-8 ✓	82.3 EB05 65.6 · IC025 +5.1 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=55 · ♀ 100% (drug 64%) · 100% consumer	no trial arm names this drug
Administration site swelling	61	77.3 58.5–102.2ROR 77.4 · calibrated p 1e-6 ✓	61.6 EB05 49.7 · IC025 +5.0 3/3 methods agree	No label text to screen label has no adverse-reaction text	♀ 100% (drug 64%) · 100% clinician	no trial arm names this drug
Blood pressure diastolic abnormal	457	72.2 65.2–79.8ROR 72.7 · calibrated p 1e-6 ✓	59.2 EB05 54.8 · IC025 +5.6 3/3 methods agree	Lab value / disease marker	serious n=446 · 90% clinician	no trial arm names this drug
Temperature regulation disorder	354	64.5 57.6–72.2ROR 64.8 · calibrated p 3e-6 ✓	53.9 EB05 49.4 · IC025 +5.5 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=354 · ♀ 100% (drug 64%)	no trial arm names this drug
Infusion site mass	158	57.9 48.9–68.6ROR 58.1 · calibrated p 6e-6 ✓	49.1 EB05 43.0 · IC025 +5.2 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=118	no trial arm names this drug
Blood pressure systolic abnormal	359	56.2 50.2–62.8ROR 56.5 · calibrated p 7e-6 ✓	48.0 EB05 44.0 · IC025 +5.3 3/3 methods agree	Lab value / disease marker	serious n=350 · 91% clinician	no trial arm names this drug
Postmortem blood drug level increased	52	55.8 41.6–74.9ROR 55.9 · calibrated p 1e-5 ✓	47.1 EB05 37.3 · IC025 +4.6 3/3 methods agree	Lab value / disease marker	serious n=52 · ♀ 100% (drug 64%)	no trial arm names this drug
Infusion site discharge	245	55.8 48.7–63.8ROR 56.0 · calibrated p 7e-6 ✓	47.6 EB05 42.8 · IC025 +5.2 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=222 · 83% consumer	no trial arm names this drug
Epidural lipomatosis	49	54.5 40.3–73.8ROR 54.6 · calibrated p 1e-5 ✓	46.1 EB05 36.3 · IC025 +4.5 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=49 · ♀ 0% (drug 64%) · 100% clinician	no trial arm names this drug
Infusion site urticaria	89	52.1 41.7–65.1ROR 52.2 · calibrated p 1e-5 ✓	44.7 EB05 37.4 · IC025 +4.8 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=55 · ♀ 100% (drug 64%)	no trial arm names this drug
Infusion site bruising	278	50.1 44.2–56.9ROR 50.4 · calibrated p 1e-5 ✓	43.5 EB05 39.4 · IC025 +5.1 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=210	no trial arm names this drug
Infusion site pruritus	378	46.0 41.3–51.2ROR 46.3 · calibrated p 2e-5 ✓	40.4 EB05 37.1 · IC025 +5.1 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=242	no trial arm names this drug
Pharyngeal paraesthesia	169	40.5 34.5–47.5ROR 40.6 · calibrated p 5e-5 ✓	36.0 EB05 31.7 · IC025 +4.8 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=167 · 100% clinician	no trial arm names this drug
Neurologic neglect syndrome	56	37.0 28.1–48.8ROR 37.0 · calibrated p 1e-4 ✓	33.0 EB05 26.4 · IC025 +4.3 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=56 · ♀ 100% (drug 64%) · 100% clinician	no trial arm names this drug
Infusion site rash	135	36.6 30.7–43.8ROR 36.7 · calibrated p 1e-4 ✓	32.9 EB05 28.5 · IC025 +4.6 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=86	no trial arm names this drug
Female genital tract fistula	169	36.3 31.0–42.5ROR 36.4 · calibrated p 1e-4 ✓	32.7 EB05 28.7 · IC025 +4.7 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=169 · ♀ 100% (drug 64%)	no trial arm names this drug
Infusion site haemorrhage	311	35.4 31.5–39.7ROR 35.5 · calibrated p 1e-4 ✓	32.0 EB05 29.1 · IC025 +4.7 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=236	no trial arm names this drug
Infusion site discomfort	97	34.9 28.3–43.1ROR 35.0 · calibrated p 1e-4 ✓	31.5 EB05 26.6 · IC025 +4.4 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=72	no trial arm names this drug
Infusion site swelling	570	34.0 31.2–37.0ROR 34.3 · calibrated p 1e-4 ✓	30.9 EB05 28.8 · IC025 +4.8 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=359	no trial arm names this drug
Lupus vulgaris	110	33.9 27.9–41.3ROR 34.0 · calibrated p 2e-4 ✓	30.7 EB05 26.2 · IC025 +4.4 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=110 · ♀ 100% (drug 64%) · 100% clinician	no trial arm names this drug
Ear pruritus	318	33.5 29.9–37.6ROR 33.7 · calibrated p 1e-4 ✓	30.4 EB05 27.7 · IC025 +4.7 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=304 · ♀ 85% (drug 64%) · 92% clinician	no trial arm names this drug
Infusion site nodule	75	30.3 23.9–38.3ROR 30.3 · calibrated p 3e-4 ✓	27.6 EB05 22.8 · IC025 +4.2 3/3 methods agree	No label text to screen label has no adverse-reaction text	–	no trial arm names this drug
Infusion site extravasation	517	30.2 27.6–33.0ROR 30.4 · calibrated p 2e-4 ✓	27.7 EB05 25.8 · IC025 +4.6 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=330	no trial arm names this drug
Anticholinergic syndrome	128	29.1 24.3–34.8ROR 29.1 · calibrated p 3e-4 ✓	26.7 EB05 23.0 · IC025 +4.3 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=127 · 100% clinician	no trial arm names this drug
Porphyria acute	102	26.6 21.7–32.5ROR 26.6 · calibrated p 6e-4 ✓	24.6 EB05 20.8 · IC025 +4.1 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=102 · ♀ 100% (drug 64%)	no trial arm names this drug
Blood pressure fluctuation	1,676	24.9 23.7–26.2ROR 25.6 · calibrated p 6e-4 ✓	23.2 EB05 22.3 · IC025 +4.4 3/3 methods agree	Lab value / disease marker	serious PRR 21.9	no trial arm names this drug
Chronic sinusitis	258	24.6 21.7–27.9ROR 24.7 · calibrated p 7e-4 ✓	22.9 EB05 20.7 · IC025 +4.3 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=242 · ♀ 94% (drug 64%)	no trial arm names this drug
Poor venous access	709	24.6 22.8–26.5ROR 24.8 · calibrated p 7e-4 ✓	22.9 EB05 21.5 · IC025 +4.4 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=630	no trial arm names this drug
Food allergy	518	24.5 22.4–26.8ROR 24.7 · calibrated p 7e-4 ✓	22.9 EB05 21.3 · IC025 +4.3 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=507 · ♀ 97% (drug 64%)	no trial arm names this drug
Infusion site erythema	554	23.9 21.9–26.0ROR 24.1 · calibrated p 8e-4 ✓	22.3 EB05 20.8 · IC025 +4.3 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=347	no trial arm names this drug
Carotid artery thrombosis	57	23.8 18.2–31.2ROR 23.8 · calibrated p 0.001 ✓	22.1 EB05 17.7 · IC025 +3.8 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=57 · ♀ 100% (drug 64%) · 100% clinician	no trial arm names this drug
Infusion site pain	817	22.8 21.2–24.4ROR 23.1 · calibrated p 0.001 ✓	21.3 EB05 20.1 · IC025 +4.3 3/3 methods agree	No label text to screen label has no adverse-reaction text	age-adj. PRR 17.0 · serious n=530	no trial arm names this drug
Deep vein thrombosis postoperative	125	22.7 18.9–27.2ROR 22.7 · calibrated p 0.001 ✓	21.2 EB05 18.3 · IC025 +4.0 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=125 · ♀ 100% (drug 64%)	no trial arm names this drug
Blood pressure diastolic decreased	469	22.5 20.5–24.7ROR 22.6 · calibrated p 0.001 ✓	21.1 EB05 19.5 · IC025 +4.2 3/3 methods agree	Lab value / disease marker	serious PRR 16.6 · 91% clinician	no trial arm names this drug
Infusion site discolouration	54	22.3 16.9–29.3ROR 22.3 · calibrated p 0.001 ✓	20.8 EB05 16.5 · IC025 +3.7 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=42 · ♀ 100% (drug 64%)	no trial arm names this drug
Radiculopathy	165	22.2 19.0–26.0ROR 22.3 · calibrated p 0.001 ✓	20.8 EB05 18.3 · IC025 +4.0 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=165 · ♀ 100% (drug 64%)	no trial arm names this drug
Infusion site irritation	77	22.0 17.5–27.7ROR 22.0 · calibrated p 0.001 ✓	20.6 EB05 17.0 · IC025 +3.8 3/3 methods agree	No label text to screen label has no adverse-reaction text	serious n=47	no trial arm names this drug
Incorrect drug administration rate	259	21.7 19.2–24.6ROR 21.8 · calibrated p 0.001 ✓	20.4 EB05 18.4 · IC025 +4.1 3/3 methods agree	Reporting / coding artifact	serious n=214	no trial arm names this drug

Clinical concept groups

MedDRA splits one clinical problem across several terms (e.g. "neutropenia", "neutrophil count decreased", "agranulocytosis"), which dilutes term-level signals. These rows count reports with any term in a concept group (an exact union, not a sum), compared with all other drugs. Groups are hand-built and listed in the methods.

Concept	Reports	PRR 95% CI	Reading
Suicidality	3,297	4.54.4–4.7	signal
Serious infection	7,135	3.13.0–3.2	signal
Opportunistic infection	1,223	3.02.9–3.2	signal
Neutropenia / agranulocytosis	2,077	2.82.7–2.9	signal
Anaphylaxis / angioedema	1,025	2.72.6–2.9	signal
Anaemia	1,816	2.01.9–2.1	raised
Fall / fracture	2,170	1.91.8–2.0	raised
Thrombocytopenia	1,210	1.81.7–1.9	raised
Arrhythmia / qt	1,049	1.81.7–1.9	raised
Liver injury	1,621	1.81.7–1.9	raised
Interstitial lung disease	514	1.81.6–2.0	raised
Seizure	1,023	1.71.6–1.9	raised
Pancreatitis	350	1.51.3–1.6	raised
Hyponatraemia	334	1.41.2–1.5	raised
Gi bleeding	710	1.31.2–1.4	raised
Venous thromboembolism	835	1.31.2–1.4	raised

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
Off label use (used outside approved label)	8,239	3.2 3.1–3.3ROR 3.5 · calibrated p 0.479	3.2 EB05 3.1 · IC025 +1.6 3/3 methods agree	Reporting / coding artifact	age-adj. PRR 2.8 · serious PRR 4.1	no trial arm names this drug
Headache	5,326	2.9 2.8–2.9ROR 3.0 · calibrated p 0.617	2.8 EB05 2.8 · IC025 +1.5 3/3 methods agree	No label text to screen label has no adverse-reaction text	age-adj. PRR 2.3 · serious PRR 3.3	no trial arm names this drug
Fatigue (tiredness)	5,270	2.3 2.2–2.3ROR 2.4 · calibrated p 0.861	2.3 EB05 2.2 · IC025 +1.1 3/3 methods agree	No label text to screen label has no adverse-reaction text	age-adj. PRR 2.1 · serious PRR 2.6	no trial arm names this drug
Nausea	4,673	2.0 1.9–2.0ROR 2.1 · calibrated p 0.978	2.0 EB05 1.9 · IC025 +0.9	No label text to screen label has no adverse-reaction text	age-adj. PRR 1.8 · serious PRR 2.3	no trial arm names this drug
Pain	4,152	2.3 2.2–2.3ROR 2.4 · calibrated p 0.879	2.3 EB05 2.2 · IC025 +1.1 3/3 methods agree	No label text to screen label has no adverse-reaction text	age-adj. PRR 2.4 · serious PRR 2.3	no trial arm names this drug
Drug ineffective (drug did not work)	4,010	1.0 1.0–1.0ROR 1.0 · calibrated p 0.318	1.0 EB05 1.0 · IC025 -0.0 PRR-only: not supported by EBGM or IC	Reporting / coding artifact	age-adj. PRR 1.2 · serious PRR 2.0	no trial arm names this drug
Toxicity to various agents	3,778	7.7 7.4–7.9ROR 8.1 · calibrated p 0.064	7.5 EB05 7.3 · IC025 +2.9 3/3 methods agree	No label text to screen label has no adverse-reaction text	age-adj. PRR 6.9 · serious PRR 5.8 · 95% clinician	no trial arm names this drug
Sinusitis	3,733	12.5 12.2–13.0ROR 13.3 · calibrated p 0.011 ✓	12.1 EB05 11.8 · IC025 +3.5 3/3 methods agree	No label text to screen label has no adverse-reaction text	age-adj. PRR 8.6 · serious PRR 10.9	no trial arm names this drug
Pyrexia (fever)	3,540	3.4 3.3–3.6ROR 3.6 · calibrated p 0.464	3.4 EB05 3.3 · IC025 +1.7 3/3 methods agree	No label text to screen label has no adverse-reaction text	age-adj. PRR 2.9 · serious PRR 2.8	no trial arm names this drug
Dyspnoea (shortness of breath)	3,522	2.1 2.0–2.2ROR 2.2 · calibrated p 0.977	2.1 EB05 2.0 · IC025 +1.0 3/3 methods agree	No label text to screen label has no adverse-reaction text	age-adj. PRR 2.0 · serious PRR 1.9	no trial arm names this drug
Infusion related reaction (reaction during infusion)	3,473	18.5 17.9–19.1ROR 19.5 · calibrated p 0.002 ✓	17.5 EB05 17.1 · IC025 +4.1 3/3 methods agree	No label text to screen label has no adverse-reaction text	age-adj. PRR 15.6 · serious PRR 13.7	no trial arm names this drug
Pneumonia (lung infection)	3,230	3.4 3.2–3.5ROR 3.5 · calibrated p 0.488	3.3 EB05 3.2 · IC025 +1.7 3/3 methods agree	No label text to screen label has no adverse-reaction text	age-adj. PRR 3.1 · serious PRR 2.6	no trial arm names this drug
Inappropriate schedule of product administration	3,134	6.0 5.8–6.2ROR 6.3 · calibrated p 0.134	5.9 EB05 5.7 · IC025 +2.5 3/3 methods agree	Reporting / coding artifact	age-adj. PRR 5.3 · serious PRR 10.4	no trial arm names this drug
Arthralgia (joint pain)	3,082	2.5 2.4–2.6ROR 2.6 · calibrated p 0.783	2.5 EB05 2.4 · IC025 +1.3 3/3 methods agree	No label text to screen label has no adverse-reaction text	age-adj. PRR 2.2 · serious PRR 3.1	no trial arm names this drug
Pruritus (itching)	2,969	2.6 2.5–2.7ROR 2.7 · calibrated p 0.726	2.6 EB05 2.5 · IC025 +1.3 3/3 methods agree	No label text to screen label has no adverse-reaction text	age-adj. PRR 2.5 · serious PRR 3.7	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 headache, fatigue, nausea, pain, toxicity to various agents, sinusitis. 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, 1,213 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 2026-10-14. 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.