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Diphenhydramine Side Effects

The most commonly reported side effects of diphenhydramine include off label use, fatigue, and nausea, based on 174,304 FDA adverse event reports from 2004 to 2025. 7.0% of reports found the drug to be ineffective.

Diphenhydramine side effects

Percentages show how often each reaction appears relative to total reports for diphenhydramine.

1
Off Label Use10.0%17,416
2
Fatigue8.8%15,258
3
Nausea7.5%13,029
4
Headache7.4%12,845
5
Drug Ineffective7.0%12,238
6
Pain6.3%10,959
7
Dyspnoea5.4%9,496
8
Pruritus5.4%9,377
9
Infusion Related Reaction5.2%9,006
10
Arthralgia5.0%8,722
11
Diarrhoea4.8%8,327
12
Rash4.7%8,176
13
Pyrexia4.3%7,452
14
Malaise4.1%7,222
15
Cough4.0%7,025

These are voluntary reports and do not establish that diphenhydramine caused these reactions.

Report severity

68.9%Serious120,150 reports
27.8%Hospitalizations48,506 reports
13.7%Fatal23,889 reports

Seriousness is determined by the reporter, not by OpenClaim.

Diphenhydramine drug interactions

Other drugs that appear in adverse event reports alongside diphenhydramine. Drugs flagged as a suspected cause appear in the first column. Drugs taken at the same time but not suspected appear in the second.

Also suspected

1
Rituximab12.4%21,543
2
Infliximab5.3%9,240
3
Acetaminophen5.1%8,862
4
Ibuprofen4.6%8,046
5
Prednisone3.2%5,535
6
Adalimumab2.9%5,068
7
Methotrexate2.8%4,893
8
Lenalidomide2.7%4,662
9
Methylprednisolone2.3%4,081
10
Pantoprazole-sodium2.3%4,069
11
Tocilizumab2.3%4,054
12
Cetirizine-hydrochloride2.2%3,844
13
Naproxen2.0%3,468
14
Oxycodone2.0%3,437
15
Etanercept1.9%3,225

Taken alongside

1
Acetaminophen41.6%72,476
2
Methylprednisolone14.6%25,393
3
Epinephrine13.7%23,801
4
Ergocalciferol13.6%23,695
5
Prednisone13.4%23,393
6
Albuterol12.1%21,063
7
Aspirin11.4%19,894
8
Ondansetron10.7%18,677
9
Levothyroxine-sodium9.9%17,221
10
Dexamethasone9.1%15,814
11
Fluticasone9.0%15,743
12
Omeprazole8.6%15,032
13
Ibuprofen8.3%14,462
14
Sodium-chloride8.1%14,144
15
Gabapentin7.9%13,796

Co-occurrence in adverse event reports does not establish a drug interaction. Patients often take multiple medications, and these lists reflect prescribing patterns rather than causal relationships. Consult a healthcare provider about potential drug interactions.

Who reports diphenhydramine side effects

57.2% of diphenhydramine adverse event reports involve female patients and 29.1% involve male patients. The largest age group is adult at 64%. These figures reflect who reports side effects, not underlying risk.

Sex

Female57.2%
Male29.1%
Unknown13.8%

Age group

< 20.8%
2–113.7%
12–173.7%
18–6464.4%
65+27.3%

What is diphenhydramine used for

Conditions and purposes for which patients were taking diphenhydramine when the adverse event was reported.

Abdominal DiscomfortAbdominal NeoplasmAbdominal PainAbdominal Pain UpperAbdominal RigidityAbnormal BehaviourAbnormal FaecesAbnormal Sensation In EyeAbnormal Sleep-related EventAbscessAcarodermatitisAccident At WorkAccidental Drug Intake By ChildAccidental ExposureAccidental Exposure To Product

Showing 15 of 1,698 indications

Diphenhydramine brand names and reporting trend

Diphenhydramine is sold under brand names including Ibuprofen And Diphenhydramine Citrate, Naproxen Sodium And Diphenhydramine Hydrochloride.

Brand names

Ibuprofen And Diphenhydramine Citrate230
Naproxen Sodium And Diphenhydramine Hydrochloride4

Quarterly reports (20042025)

20052010201520202025

An upward trend reflects increased FAERS reporting overall, not necessarily increased risk.

Taking diphenhydramine with another medication?

Ask OpenClaim about your specific drug combination. Get a sourced report using FDA data, drug labels, and medical literature.