DIPHENHYDRAMINE

65/100 · Elevated

Manufactured by AAA Pharmaceutical, Inc.

Diphenhydramine Adverse Events: Common Mild Reactions with Serious Incidents

181,665 FDA adverse event reports analyzed

Last updated: 2026-05-12

About DIPHENHYDRAMINE

DIPHENHYDRAMINE is a medication tracked in the FDA Adverse Event Reporting System (FAERS), manufactured by AAA Pharmaceutical, Inc.. Based on analysis of 181,665 FDA adverse event reports, DIPHENHYDRAMINE has a safety score of 65 out of 100. This moderate score indicates a notable volume of adverse event reports that patients and providers should be aware of. The most commonly reported adverse reactions for DIPHENHYDRAMINE include OFF LABEL USE, HEADACHE, FATIGUE, NAUSEA, PAIN. This page provides a comprehensive breakdown of reported side effects, safety signals, patient demographics, and AI-powered safety analysis for DIPHENHYDRAMINE.

AI Safety Analysis

Diphenhydramine has a safety concern score of 65 out of 100, placing it in the elevated concern category based on analysis of FDA adverse event data. The FDA has received approximately 181,665 adverse event reports for this medication, which is primarily manufactured by Aaa Pharmaceutical, Inc..

The most commonly reported adverse events include Off Label Use, Headache, Fatigue. Of classified reports, 76.0% were designated as serious by the FDA, meaning they involved hospitalization, disability, or other significant medical outcomes. Most common reactions include headache, fatigue, and nausea, which are generally mild.

Serious adverse events, such as pneumonia, heart arrest, and death, are reported but less frequent. Drug interactions and misuse are significant concerns, particularly with intentional misuse and overdose. The majority of reactions are non-serious, but the presence of serious events warrants ongoing monitoring.

Patients taking Diphenhydramine should monitor for the commonly reported side effects and contact their healthcare provider if they experience any unusual symptoms. Diphenhydramine can interact with other medications, potentially leading to increased side effects or reduced efficacy. Misuse, including intentional overdose, is a significant risk. This analysis is based on voluntary FDA adverse event reports and should not replace professional medical advice.

Safety Score: 65/100

Diphenhydramine received a safety concern score of 65/100 (elevated concern). This is based on a 76.0% serious event ratio across 60,510 classified reports. The score accounts for 181,665 total adverse event reports and 100 distinct reaction types. This elevated score indicates a notable proportion of serious adverse events and warrants careful monitoring.

Top Adverse Reactions

OFF LABEL USE7,770 reports
HEADACHE5,139 reports
FATIGUE5,076 reports
NAUSEA4,484 reports
PAIN4,013 reports
DRUG INEFFECTIVE3,867 reports
SINUSITIS3,668 reports
TOXICITY TO VARIOUS AGENTS3,497 reports
DYSPNOEA3,389 reports
PYREXIA3,386 reports
INFUSION RELATED REACTION3,345 reports
PNEUMONIA3,100 reports
ARTHRALGIA3,001 reports
INAPPROPRIATE SCHEDULE OF PRODUCT ADMINISTRATION2,918 reports
COMPLETED SUICIDE2,811 reports
PRURITUS2,807 reports
MALAISE2,803 reports
COUGH2,748 reports
BLOOD PRESSURE INCREASED2,724 reports
INTENTIONAL PRODUCT USE ISSUE2,642 reports
NASOPHARYNGITIS2,595 reports
CONDITION AGGRAVATED2,580 reports
COVID 192,570 reports
DIARRHOEA2,559 reports
RASH2,502 reports
VOMITING2,484 reports
WEIGHT DECREASED2,464 reports
HYPERTENSION2,391 reports
DEATH2,293 reports
DIZZINESS2,256 reports
PRODUCT DOSE OMISSION ISSUE2,159 reports
URINARY TRACT INFECTION2,049 reports
WEIGHT INCREASED2,002 reports
BACK PAIN1,919 reports
FALL1,905 reports
ERYTHEMA1,866 reports
DRUG ABUSE1,834 reports
ASTHENIA1,769 reports
INFECTION1,690 reports
BLOOD PRESSURE FLUCTUATION1,664 reports
PRODUCT USE ISSUE1,632 reports
PAIN IN EXTREMITY1,622 reports
DRUG HYPERSENSITIVITY1,604 reports
HYPOTENSION1,586 reports
UPPER RESPIRATORY TRACT INFECTION1,580 reports
URTICARIA1,571 reports
HYPERSENSITIVITY1,551 reports
ANXIETY1,533 reports
BRONCHITIS1,503 reports
ABDOMINAL PAIN1,497 reports
INFLUENZA1,422 reports
RHEUMATOID ARTHRITIS1,404 reports
FEBRILE NEUTROPENIA1,391 reports
CHILLS1,342 reports
OVERDOSE1,337 reports
HEART RATE INCREASED1,247 reports
OXYGEN SATURATION DECREASED1,223 reports
CONSTIPATION1,218 reports
CHEST DISCOMFORT1,210 reports
CHEST PAIN1,201 reports
SOMNOLENCE1,189 reports
PRODUCT USE IN UNAPPROVED INDICATION1,183 reports
OROPHARYNGEAL PAIN1,162 reports
ILLNESS1,136 reports
FLUSHING1,132 reports
JOINT SWELLING1,119 reports
HEART RATE DECREASED1,116 reports
PERIPHERAL SWELLING1,116 reports
INSOMNIA1,094 reports
ASTHMA1,074 reports
THROAT IRRITATION1,046 reports
EAR INFECTION1,009 reports
HYPERHIDROSIS1,002 reports
BLOOD PRESSURE SYSTOLIC INCREASED992 reports
DECREASED APPETITE949 reports
MIGRAINE935 reports
ANAEMIA927 reports
HYPOAESTHESIA918 reports
ABDOMINAL PAIN UPPER914 reports
TACHYCARDIA907 reports
CARDIAC ARREST900 reports
GAIT DISTURBANCE856 reports
FEELING ABNORMAL852 reports
CARDIO RESPIRATORY ARREST833 reports
ABDOMINAL DISCOMFORT811 reports
INFUSION SITE PAIN806 reports
MUSCLE SPASMS788 reports
HEPATIC ENZYME INCREASED785 reports
CONTUSION759 reports
PARAESTHESIA757 reports
ALOPECIA748 reports
DEHYDRATION747 reports
TREMOR737 reports
THROMBOCYTOPENIA720 reports
INTENTIONAL PRODUCT MISUSE718 reports
SEPSIS709 reports
MUSCULAR WEAKNESS705 reports
NASAL CONGESTION704 reports
SWELLING699 reports
ACUTE KIDNEY INJURY698 reports

Key Safety Signals

  • Intentional misuse and overdose are key safety signals.
  • Heart-related issues, including arrest, are serious safety concerns.
  • Pneumonia and other infections are notable adverse events.
  • Drug ineffectiveness and inappropriate schedule of administration are frequent issues.

Patient Demographics

Adverse event reports by sex: Female: 33,647, Male: 18,719, Unknown: 94. The most frequently reported age groups are age 58 (922 reports), age 57 (804 reports), age 50 (790 reports). These demographics reflect reporting patterns and may not represent the full patient population.

Report Outcomes

Out of 60,510 classified reports for DIPHENHYDRAMINE:

  • Serious: 46,005 reports (76.0%) — includes hospitalization, disability, life-threatening events, or death
  • Non-Serious: 14,505 reports (24.0%)
Serious 76.0%Non-Serious 24.0%

The FDA classifies an adverse event as “serious” if it results in death, hospitalization, disability, congenital anomaly, or requires intervention to prevent permanent damage.

Demographics Breakdown

Reports by Sex

Female33,647 (64.1%)
Male18,719 (35.7%)
Unknown94 (0.2%)

Reports by Age

Age 58922 reports
Age 57804 reports
Age 50790 reports
Age 61788 reports
Age 65772 reports
Age 54771 reports
Age 60766 reports
Age 59737 reports
Age 56732 reports
Age 53703 reports
Age 62697 reports
Age 69693 reports
Age 63688 reports
Age 71686 reports
Age 70680 reports
Age 51665 reports
Age 64664 reports
Age 66664 reports
Age 67663 reports
Age 55651 reports

Demographics reflect voluntary FDA adverse event reporting patterns and may not represent the full patient population.

Drug Interactions & Warnings

Diphenhydramine can interact with other medications, potentially leading to increased side effects or reduced efficacy. Misuse, including intentional overdose, is a significant risk.

What You Should Know

If you are taking Diphenhydramine, here are important things to know. The most commonly reported side effects include off label use, headache, fatigue, nausea, pain. While many of these may be mild and temporary, you should contact your healthcare provider if any symptoms are severe or persistent. Always follow the prescribed dosage and duration of use. Report any unusual symptoms or side effects to your healthcare provider immediately. If you experience a serious adverse reaction, seek emergency medical attention immediately or call 911. You can report side effects to the FDA's MedWatch program at 1-800-FDA-1088.

Regulatory Context

The FDA continues to monitor Diphenhydramine for safety, particularly in elderly populations and those with pre-existing conditions. Regularly review medication instructions and avoid self-medicating without a prescription.

Frequently Asked Questions

How many adverse event reports has the FDA received for Diphenhydramine?

The FDA has received approximately 181,665 adverse event reports associated with Diphenhydramine. These reports come from healthcare professionals, consumers, and manufacturers through the FDA Adverse Event Reporting System (FAERS). Note that the number of reports does not directly indicate the frequency of side effects, as adverse events are voluntarily reported and may be underrepresented.

What are the most commonly reported side effects of Diphenhydramine?

The most frequently reported adverse events for Diphenhydramine include Off Label Use, Headache, Fatigue, Nausea, Pain. By volume, the top reported reactions are: Off Label Use (7,770 reports), Headache (5,139 reports), Fatigue (5,076 reports). These figures reflect FDA adverse event reports and may not represent the true incidence rate of these side effects in all patients taking Diphenhydramine.

What percentage of Diphenhydramine adverse event reports are serious?

Out of 60,510 classified reports, 46,005 (76.0%) were classified as serious and 14,505 as non-serious. The FDA classifies an event as "serious" if it results in death, hospitalization, disability, or other medically significant outcomes. A higher serious-event ratio warrants closer attention but does not necessarily mean the drug is unsafe.

Who reports adverse events for Diphenhydramine (by sex)?

Adverse event reports for Diphenhydramine break down by patient sex as follows: Female: 33,647, Male: 18,719, Unknown: 94. This distribution reflects reporting patterns rather than actual risk differences between groups. Reporting rates can be influenced by prescribing patterns, disease demographics, and reporting behavior.

What age groups report the most side effects for Diphenhydramine?

The most frequently reported age groups for Diphenhydramine adverse events are: age 58: 922 reports, age 57: 804 reports, age 50: 790 reports, age 61: 788 reports, age 65: 772 reports. Age-related reporting patterns can reflect both the demographics of the patient population and potential age-related susceptibility to certain side effects.

Who manufactures Diphenhydramine?

The primary manufacturer associated with Diphenhydramine adverse event reports is Aaa Pharmaceutical, Inc.. Multiple manufacturers may produce generic versions of this drug. The manufacturer listed reflects the most frequently reported brand in FDA adverse event data.

What other side effects have been reported for Diphenhydramine?

Beyond the most common reactions, other reported adverse events for Diphenhydramine include: Drug Ineffective, Sinusitis, Toxicity To Various Agents, Dyspnoea, Pyrexia. Less common side effects can still be clinically significant. Patients should report any unusual symptoms to their healthcare provider.

How do I report a side effect from Diphenhydramine?

You can report adverse events from Diphenhydramine to the FDA through their MedWatch program at www.fda.gov/medwatch, by calling 1-800-FDA-1088, or by completing Form FDA 3500. Healthcare professionals, consumers, and manufacturers can all submit reports. Reporting helps the FDA monitor drug safety after approval.

What is Diphenhydramine's safety score and what does it mean?

Diphenhydramine has a safety concern score of 65 out of 100 (elevated concern). This score is calculated from the ratio of serious to non-serious adverse events, the diversity of reported reactions, and the overall volume of reports relative to usage. Most common reactions include headache, fatigue, and nausea, which are generally mild.

What are the key safety signals for Diphenhydramine?

Key safety signals identified in Diphenhydramine's adverse event data include: Intentional misuse and overdose are key safety signals.. Heart-related issues, including arrest, are serious safety concerns.. Pneumonia and other infections are notable adverse events.. Drug ineffectiveness and inappropriate schedule of administration are frequent issues.. These signals are derived from patterns in FDA reports and should be discussed with a healthcare provider for personalized assessment.

Does Diphenhydramine interact with other drugs?

Diphenhydramine can interact with other medications, potentially leading to increased side effects or reduced efficacy. Misuse, including intentional overdose, is a significant risk. Always inform your healthcare provider about all medications, supplements, and over-the-counter drugs you are taking before starting Diphenhydramine.

What should patients know before taking Diphenhydramine?

Always follow the prescribed dosage and duration of use. Report any unusual symptoms or side effects to your healthcare provider immediately.

Are Diphenhydramine side effects well-documented?

Diphenhydramine has 181,665 adverse event reports on file with the FDA. Serious adverse events, such as pneumonia, heart arrest, and death, are reported but less frequent. The volume of reports for Diphenhydramine reflects both the drug's usage level and the vigilance of the reporting community.

What is the FDA's position on Diphenhydramine?

The FDA continues to monitor Diphenhydramine for safety, particularly in elderly populations and those with pre-existing conditions. Regularly review medication instructions and avoid self-medicating without a prescription. For the most current regulatory information, check the FDA's drug labeling database or consult your pharmacist.

Related Drugs

Drugs related to DIPHENHYDRAMINE based on therapeutic use, drug class, or shared indications:

AcetaminophenIbuprofenAspirin
Important Disclaimer: This content is generated by AI analysis of FDA adverse event reports and is provided for informational purposes only. It is not medical advice. Adverse event reports submitted to the FDA do not prove that a medication caused the reported side effect. Always consult your healthcare provider before starting, stopping, or changing any medication. If you experience a serious side effect, contact your doctor or call 911 immediately.