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.
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
- Fatigue
Fatigue
5,076 reports
- Nausea
Nausea
4,484 reports
- Pain
Pain
4,014 reports
- Sinusitis
Sinusitis
3,668 reports
- Toxicity To Various Agents
Toxicity To Various Agents
3,497 reports
- Dyspnoea
Dyspnoea
3,387 reports
- Pyrexia
Pyrexia
3,386 reports
- Infusion Related Reaction
Infusion Related Reaction
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) 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.
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.
This is a plain-language summary of FDA-label interaction records and does not provide individual medication-combination directions.
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?
What pregnancy or breastfeeding source fields are listed for diphenhydramine?
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 →
Compare beyond drug class
Nationwide peers by FAERS volume & death-report share
Two PlainMeds-derived comparison paths for diphenhydramine: nearest FDA FAERS report volume and nearest death-report share among drugs with at least 1,000 logged reports, excluding same-class neighbors listed above. Counts reflect reporting volume, not proven individual harm.
Similar FAERS report volume
Nearest drugs by total FAERS reports. This record: 60,533.
Similar death-report share
Nearest drugs by FAERS death-report share. This record: 18.77%.
- chlorpromazine Δ 0.04 pts · 6,862 reports · Typical Antipsychotic (Phenothiazine) 18.73%death share
- phytonadione Δ 0.10 pts · 8,078 reports · Vitamin K Supplement 18.67%death share
- gentamicin Δ 0.12 pts · 12,687 reports · Aminoglycoside Antibiotic 18.65%death share
- linezolid Δ 0.18 pts · 28,005 reports · Oxazolidinone Antibiotic 18.58%death share
Medication Guides
Understanding Drug Interactions
How CYP450 enzymes, inhibitors, and inducers affect your medications
Generic vs Brand Name Drugs
FDA requirements, cost savings, and when the difference matters
Pain Relievers Compared
NSAIDs vs acetaminophen, which OTC pain reliever to use
Narrow Therapeutic Index Drugs
FDA bioequivalence and label-record context for narrow therapeutic index medicines
Common Drug Interactions
Dangerous medication combinations and how to protect yourself
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 are separate source-record fields. This page is a public FDA/CMS registry and does not provide medical, treatment, substitution, or medication-change directions.
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. This registry does not provide medication decisions.
Last updated: January 22, 2025
PlainMeds is rendered directly from FDA openFDA/FAERS extracts, DailyMed labels, and CMS drug-pricing files, no number is typed in by an editor. FAERS counts, recalls, shortages, and price figures on this page are queried live from those federal extracts. See our editorial standards & corrections policy, the methodology behind these numbers, or report a data error. Data current as of 2026-05-15. Primary sources: openFDA / FAERS, DailyMed and CMS Part B ASP.
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 from the source snapshot dated . See our methodology for per-source dates and refresh cadence. Spot a figure that looks wrong? Report a data issue.
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