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Drug side effects

diphenhydramine Side Effects

The reactions most often reported to the FDA for diphenhydramine (also sold as Benadryl), with demographics, serious outcomes, and reporting trends.

Data updated 2026-05-15

60,533
FAERS reports

Data from the FDA Adverse Event Reporting System (FAERS), 2003 to 2025. A FAERS report records a temporal association, not proof of cause. See our methodology for how figures are compiled and de-duplicated.

The most commonly reported side effects of diphenhydramine come from 60,533 reports to the FDA, broken down here by frequency, patient demographics, and serious outcomes.

This page analyzes 60,533 reports to the FDA Adverse Event Reporting System (FAERS) for diphenhydramine (Benadryl): the reactions reported most often, who reported them, serious outcomes such as hospitalization, and year-over-year trends. A FAERS report does not prove the drug caused the effect, and report volume tracks how widely a drug is used, not how likely an effect is for any one person. Educational information, not medical advice.

Total Reports

60,533

Reports Mentioning Death

11,360

18.8% of reports — not proof the medicine caused the death

Hospitalizations

19,529

32.3% of reports

Top Indication

Product Used For Unknown Indication

Most Reported Adverse Reactions

HEADACHE
5,138
FATIGUE
5,076
NAUSEA
4,484
PAIN
4,014
SINUSITIS
3,668
TOXICITY TO VARIOUS AGENTS
3,497
DYSPNOEA
3,387
PYREXIA
3,386
INFUSION RELATED REACTION
3,345
PNEUMONIA
3,100
ARTHRALGIA
3,001
INAPPROPRIATE SCHEDULE OF PRODUCT ADMINISTRATION
2,918
COMPLETED SUICIDE
2,811
PRURITUS
2,806
MALAISE
2,803
COUGH
2,748
BLOOD PRESSURE INCREASED
2,724

Who Reports Side Effects

Gender Distribution

Female 33,648 (64%)
Male 18,723 (36%)
Unknown 94

Age Distribution

0-17 3,787 (10%)
18-44 10,761 (28%)
45-64 13,785 (36%)
65-74 6,439 (17%)
75+ 3,602 (9%)

Reporting Trend by Year

2003 2025

Reactions in Death Reports

Top reactions reported in 11,360 reports where death was an outcome. These are voluntarily reported and do not establish causation.

Reaction Reports
COMPLETED SUICIDE 2,805
TOXICITY TO VARIOUS AGENTS 2,776
DEATH 2,291
DRUG ABUSE 1,610
CARDIO-RESPIRATORY ARREST 781
CARDIAC ARREST 677
OVERDOSE 550
RESPIRATORY ARREST 472
PNEUMONIA 452
FATIGUE 444
DYSPNOEA 358
PAIN 356
PYREXIA 355
HEADACHE 334
HYPERTENSION 321
NAUSEA 300
INTENTIONAL PRODUCT MISUSE 297
INFUSION RELATED REACTION 289
VOMITING 282

Reactions in Hospitalization Reports

Top reactions in 19,529 reports where hospitalization was an outcome.

Reaction Reports
PNEUMONIA 2,033
NAUSEA 1,772
FATIGUE 1,710
PYREXIA 1,663
HEADACHE 1,627
PAIN 1,539
DYSPNOEA 1,534
MALAISE 1,283
VOMITING 1,224
ARTHRALGIA 1,223
FEBRILE NEUTROPENIA 1,211
DIARRHOEA 1,199
WEIGHT DECREASED 1,191
COVID-19 1,159
INAPPROPRIATE SCHEDULE OF PRODUCT ADMINISTRATION 1,153
FALL 1,148
SINUSITIS 1,098
CONDITION AGGRAVATED 1,061

Compare diphenhydramine vs azelastine →

What the FAERS Data Reveals About diphenhydramine Side Effects

The FDA Adverse Event Reporting System (FAERS) contains 60,533 voluntary reports linked to diphenhydramine and its brand equivalents (Benadryl), spanning 2003 through 2025. Of those, 11,360 (18.8%) listed death as an outcome and 19,529 (32.3%) involved hospitalization. The most common indication reported alongside adverse events was Product Used For Unknown Indication.

Demographic breakdowns help contextualize who is being exposed to the drug. Of reports with known sex, 64% were female and 36% male; age distribution skews toward 45-64, with 13,785 reports in that bracket. The single most reported reaction is headache with 5,138 submissions, followed by fatigue and nausea.

How to read these numbers

FAERS is a signal-detection tool, not a scorecard. Reports are voluntary, and a single case may list multiple suspect drugs, so numbers above should not be read as incidence rates or per-patient risk. Widely prescribed drugs naturally accumulate more reports than niche therapies even when individual risk is low. These aggregates are useful for spotting patterns that merit further pharmacovigilance, not for choosing between medications. This page is for educational reference only and is not medical advice, speak with a licensed clinician about any side-effect concerns.

Drugs With a Similar FAERS Report Volume

Other medications with a total FDA adverse-event report count closest to diphenhydramine's 60,533.