Over-the-counter medication · First-Generation Antihistamine
diphenhydramine
Also sold as Benadryl. This medicine temporarily relieves symptoms from allergies or hay fever.
Data updated 2026-05-15
- 60,533
- FDA reportsOften reported
- 2
- InteractionsFew interactions
- 6
- Recall records
What the data shows
diphenhydramine (Benadryl) is an over-the-counter First-Generation Antihistamine, more reported than most tracked drugs (60,533 FDA reports), with 2 documented drug interactions.
Reporting volume reflects how widely a drug is used and studied, not how dangerous it is, a FAERS report documents a temporal association, never proof of cause.
diphenhydramine (Benadryl) is an over-the-counter First-Generation Antihistamine. This medicine temporarily relieves symptoms from allergies or hay fever.
Diphenhydramine, also known as Benadryl, is an antihistamine medicine. It helps relieve allergy and cold symptoms.
Verify with FDA → · CMS NADAC pricing →
Drug Pricing (NADAC)
Generic Price
$0.01/unit
Generic Available
Yes (13 manufacturers)
Pricing data from NADAC (CMS), effective December 18, 2024. Compare all drug costs →
What it does
This medicine temporarily relieves symptoms from allergies or hay fever.
Common side effects
Headache, Fatigue, Nausea
Key warnings
No specific warnings noted. Always follow your prescriber's instructions.
The sections below are summarized in plain English from diphenhydramine's FDA-approved prescribing information. They describe what the official label says, and are not personal medical advice.
How It Works
Diphenhydramine blocks histamine, a natural substance that your body makes during an allergic reaction. By blocking histamine, it reduces allergy symptoms. It can also dry up nasal passages to relieve a runny nose.
How to Take It
Take this medicine every 4 to 6 hours as needed. Do not take more than 6 doses in 24 hours. Children under 4 years old should not use this medicine. Children 4 to under 6 years old should not use this medicine unless a doctor tells you to. Children 6 to under 12 years old can take 1 to 2 teaspoonfuls (5 ml to 10 ml).
This is a plain-language summary of diphenhydramine's FDA labeling, not individualized dosing advice. Ask a pharmacist or prescriber before changing how you take this medication.
Pregnancy & Breastfeeding
If you are pregnant or breastfeeding, talk to your doctor before using this medicine. It is important to weigh the benefits and risks with your doctor.
This is a plain-language summary of diphenhydramine's FDA labeling, not individualized advice. Ask a pharmacist or prescriber about pregnancy or breastfeeding on this medication.
Missed Dose
If you miss a dose, take it as soon as you remember. Do not take more than 6 doses in 24 hours.
This is a plain-language summary of diphenhydramine's FDA labeling, not individualized advice. Ask a pharmacist or prescriber what to do about your specific missed dose.
Storage
Store at room temperature away from moisture and heat.
Side Effects (from patient reports)
Based on 60,533 FDA adverse event reports.
Most-reported reactions
Adverse reactions in FAERS for diphenhydramine, by number of reports
- Headache
Headache
5,138 reports
- Tiredness
Tiredness
5,076 reports
- Feeling sick to your stomach
Feeling sick to your stomach
4,484 reports
- Pain
Pain
4,014 reports
- Sinus infection
Sinus infection
3,668 reports
- Poisoning from different substances
Poisoning from different substances
3,497 reports
- Difficulty breathing
Difficulty breathing
3,387 reports
- Fever
Fever
3,386 reports
- Reaction to the medicine given through a vein
Reaction to the medicine given through a vein
3,345 reports
- Pneumonia
Pneumonia
3,100 reports
What this shows Bars show how often each reaction was reported, not how likely it is to happen, a report records a temporal association, never proof that the drug caused it.
Reports over time
Adverse-event reports filed for diphenhydramine each year to the FDA Adverse Event Reporting System (FAERS).
Year-to-year volume tracks usage, prescribing, and scrutiny, not a change in per-patient risk. Source: FDA FAERS.
Where diphenhydramine sits
diphenhydramine has more FDA adverse-event reports than 77% of the drugs FAERS tracks. A high position reflects how widely a drug is used and watched, not how dangerous it is.
Percentile across all drugs PlainMeds tracks by FAERS report volume. The dot is diphenhydramine; the line is the median (50th percentile).
FDA Adverse Event Report Analysis
Detailed analysis of 60,533 reports from the FDA Adverse Event Reporting System (FAERS). Reports span 2003–2025.
Total Reports
60,533
Reports Mentioning Death
11,360
18.8% of reports — not proof of cause
Hospitalization Reports
19,529
Top Indication
Product Used For Unknown Indication
Gender Distribution
Age Distribution
Most Reported Adverse Reactions (FAERS)
| # | Reaction | Reports |
|---|---|---|
| 2 | HEADACHE | 5,138 |
| 3 | FATIGUE | 5,076 |
| 4 | NAUSEA | 4,484 |
| 5 | PAIN | 4,014 |
| 7 | SINUSITIS | 3,668 |
| 8 | TOXICITY TO VARIOUS AGENTS | 3,497 |
| 9 | DYSPNOEA | 3,387 |
| 10 | PYREXIA | 3,386 |
| 11 | INFUSION RELATED REACTION | 3,345 |
| 12 | PNEUMONIA | 3,100 |
| 13 | ARTHRALGIA | 3,001 |
| 14 | INAPPROPRIATE SCHEDULE OF PRODUCT ADMINISTRATION | 2,918 |
| 15 | COMPLETED SUICIDE | 2,811 |
| 16 | PRURITUS | 2,806 |
| 17 | MALAISE | 2,803 |
Reactions in Death Reports
Reactions in Hospitalization Reports
Source: FDA FAERS (Adverse Event Reporting System) FDA FAERS (Adverse Event Reporting System) Reports are voluntary and do not establish causation
Known Drug Interactions
Anticholinergic Drugs Concomitant treatment with clozapine and other drugs with anticholinergic activity (e.g., benztropine, cyclobenzaprine, diphenhydramine) can increase the risk for anticholinergic toxicity and severe gastrointestinal adverse reactions related to hypomotility.
Mechanism: These two drugs both block certain signals in the body, which can lead to a 'double dose' of side effects like extreme sleepiness and severe constipation. This happens because both medications have similar drying and slowing effects on the body.
What to do: Be careful when using these together and watch for signs of severe constipation or confusion. Consult your healthcare provider before taking over-the-counter allergy or sleep aids while on clozapine.
Diphenhydramine: Diphenhydramine is reported to be a weak inhibitor of aldehyde oxidase in rat liver, but its inhibitory effects in human liver are not known. There is no pharmacokinetic interaction between zaleplon and diphenhydramine following the administration of a single dose (10 mg and 50 mg, respectively) of each drug.
Mechanism: Diphenhydramine might weakly block a liver enzyme, but studies show it does not change how the body processes zaleplon. There is no evidence that these drugs interfere with each other's levels in the blood.
What to do: No dose adjustments are usually needed when taking these two drugs together. Always inform your doctor about all medications you are using.
This is a plain-language summary of interactions documented in FDA labeling, not individualized advice. Ask a pharmacist or prescriber before combining medications.
Common Questions
What is the active ingredient?
Can I give this to my baby?
Will this medicine make me sleepy?
Can I take this with other medicines?
How long does it take to work?
Can I drive after taking this?
What if my symptoms don't improve?
Can I take this for a cough?
Can I drink alcohol while taking this?
How often can I take this?
What are the common side effects of diphenhydramine?
Does diphenhydramine interact with other medications?
What drug class is diphenhydramine?
Is diphenhydramine safe during pregnancy?
Has diphenhydramine been recalled?
Active Recalls
CGMP Deviations; detection of Nitrosamine Drug Substance-Related Impurities (NDSRI), N-nitroso-desmethyl-diphenhydramine (n-dph), above the FDA Recommended Intake Limit
Chattem Inc
CGMP Deviations: Nitrosamine Drug Substance Related Issue impurity above the daily acceptable intake limit defined by the Food and Drug Administration.
Chattem Inc
Labeling: Not Elsewhere Classified: Tablets/Capsules imprinted with wrong ID.
Akron Pharma, Inc.
Labeling: Not Elsewhere Classified: Tablets/Capsules imprinted with wrong ID.
Akron Pharma, Inc.
CGMP Deviations: product held outside appropriate storage temperature conditions.
Family Dollar Stores, Llc.
Lack of Assurance of Sterility: FDA inspection findings resulted in concerns regarding quality control processes
Lowlite Investments, Inc. D/B/A Olympia Pharmacy
Related Medications in First-Generation Antihistamine
Other drugs grouped near diphenhydramine - same-class peers and common alternatives.
azelastine
Astelin, Astepro
Azelastine nasal spray is an antihistamine medicine.
Compare with diphenhydramine →
budesonide nasal
Rhinocort
Rhinocort is a nasal spray that helps relieve allergy symptoms.
Compare with diphenhydramine →
cetirizine
Zyrtec
Cetirizine (Zyrtec) is an antihistamine medicine.
Compare with diphenhydramine →
chlorpheniramine
Chlor-Trimeton
Chlorpheniramine is an antihistamine medicine.
Compare with diphenhydramine →
ciclesonide nasal
Omnaris, Zetonna
Omnaris Nasal Spray is a medicine that helps treat allergy symptoms in your nose.
Compare with diphenhydramine →
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What the FDA Data Shows for diphenhydramine
The FDA label for diphenhydramine (sold under brand names such as Benadryl) classifies it as an over-the-counter product in the First-Generation Antihistamine class. This medicine temporarily relieves symptoms from allergies or hay fever. Official labeling lists 3 commonly reported side effects, including Headache, Fatigue, Nausea.
Post-market surveillance from the FDA Adverse Event Reporting System (FAERS) captures real-world experience. For this drug, FAERS contains 60,533 voluntary reports. The database also lists 2 documented drug interactions derived from FDA labeling, with the top-flagged interaction rated moderate severity. NADAC pricing from CMS shows a generic unit cost of $0.01.
Report counts do not establish causation, a FAERS entry documents a temporal association, not proof that the drug produced the outcome. Widely prescribed medications naturally accumulate more reports than niche therapies, so raw totals must be interpreted alongside total exposure. Shortage status, recall history (currently 6 recall records on file), and patent information further shape supply and switching decisions. This page summarizes public FDA data for educational purposes only and is not a substitute for professional medical advice, always consult a licensed healthcare provider before starting, stopping, or changing any medication.
Data Sources
Drug labeling: FDA Drug Labels (SPL/DailyMed). Adverse events: FDA Adverse Event Reporting System (FAERS). Pricing: CMS National Average Drug Acquisition Cost (NADAC).
FAERS reports are voluntary and do not establish causation. Drug interactions are derived from FDA labeling and clinical references. Always consult a healthcare professional before making medication decisions.
Last updated: January 22, 2025
Read our methodology - how this data is sourced, computed, and verified.
Data currency: FDA FAERS adverse-event reports through 2025, CMS NADAC acquisition-cost pricing effective December 2024, compiled and last refreshed May 2026. See our methodology for per-source dates and refresh cadence. Spot a figure that looks wrong? Report a correction.
All federal data sources used on this page
- FDA Orange Book - approved drug products with therapeutic equivalence. accessdata.fda.gov/cder/ob
- FDA DailyMed - NIH-hosted drug labeling for FDA-approved meds. dailymed.nlm.nih.gov
- FDA Adverse Event Reporting System (FAERS) - post-marketing safety surveillance. fda.gov/drugs/faers
- NLM RxNorm - standardized clinical drug nomenclature. nlm.nih.gov/research/umls/rxnorm
- CMS Medicare Part B Drug Average Sales Price Files - federal drug pricing data. cms.gov/medicare/part-b-drugs/asp
- FDA Drug Shortages Database - current and resolved drug shortage tracking. accessdata.fda.gov/drugshortages