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diphenhydramine

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Brand names: Benadryl

First-Generation Antihistamine OTC

Diphenhydramine, also known as Benadryl, is an antihistamine medicine. It helps relieve allergy and cold symptoms.

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

There are no boxed warnings for this medication.

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).

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.

Missed Dose

If you miss a dose, take it as soon as you remember. Do not take more than 6 doses in 24 hours.

Storage

Store at room temperature away from moisture and heat.

Side Effects (from patient reports)

Based on 44,288 FDA adverse event reports.

Using the medicine for a purpose it's not approved for
7,772
Headache
5,138
Tiredness
5,076
Feeling sick to your stomach
4,484
Pain
4,014
The medicine is not working
3,866
Sinus infection
3,668
Poisoning from different substances
3,497
Difficulty breathing
3,387
Fever
3,386

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

Death-Related Reports

11,360

Hospitalization Reports

19,529

Top Indication

Product Used For Unknown Indication

Gender Distribution

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

Age Distribution

0–17 3,787
18–44 10,761
45–64 13,785
65–74 6,439
75+ 3,602

Most Reported Adverse Reactions (FAERS)

# Reaction Reports
1 OFF LABEL USE 7,772
2 HEADACHE 5,138
3 FATIGUE 5,076
4 NAUSEA 4,484
5 PAIN 4,014
6 DRUG INEFFECTIVE 3,867
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

Reactions in Death 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
OFF LABEL USE 586
OVERDOSE 550
RESPIRATORY ARREST 472
PNEUMONIA 452

Reactions in Hospitalization Reports

OFF LABEL USE 2,542
PNEUMONIA 2,033
NAUSEA 1,772
FATIGUE 1,710
PYREXIA 1,663
HEADACHE 1,627
PAIN 1,539
DYSPNOEA 1,534
DRUG INEFFECTIVE 1,302
MALAISE 1,283

Source: FDA FAERS (Adverse Event Reporting System) FDA FAERS (Adverse Event Reporting System) Reports are voluntary and do not establish causation

Serious Warnings

There are no boxed warnings for this medication.

Known Drug Interactions

moderate clozapine

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.

Common Questions

What is the active ingredient?
The active ingredient is diphenhydramine.
Can I give this to my baby?
Do not use in children under 4 years of age.
Will this medicine make me sleepy?
Yes, this medicine can cause drowsiness.
Can I take this with other medicines?
Talk to your doctor or pharmacist before taking this with other medicines.
How long does it take to work?
It should start working within 15 to 30 minutes.
Can I drive after taking this?
Do not drive or operate machinery if you feel drowsy.
What if my symptoms don't improve?
Talk to your doctor if your symptoms do not improve after 7 days.
Can I take this for a cough?
This medicine can help with a cough caused by allergies or a cold.
Can I drink alcohol while taking this?
Avoid alcohol while taking this medicine.
How often can I take this?
Take every 4 to 6 hours as needed, but do not take more than 6 doses in 24 hours.
What are the common side effects of diphenhydramine?
The most commonly reported side effects of diphenhydramine include Headache, Fatigue, Nausea. Based on 44,288 FDA adverse event reports. Always consult your healthcare provider about potential side effects.
Does diphenhydramine interact with other medications?
Yes, diphenhydramine has 2 known drug interactions. Notable interactions include clozapine, zaleplon. Always inform your doctor about all medications you are taking.
What drug class is diphenhydramine?
diphenhydramine belongs to the First-Generation Antihistamine drug class. It is available over the counter (OTC). This medicine temporarily relieves symptoms from allergies or hay fever.
Is diphenhydramine safe during pregnancy?
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. Always consult your healthcare provider before using any medication during pregnancy or breastfeeding.
Has diphenhydramine been recalled?
There are 6 recalls associated with diphenhydramine products. CGMP Deviations; detection of Nitrosamine Drug Substance-Related Impurities (NDSRI), N-nitroso-desmethyl-diphenhydramine (n-dph), above the FDA Recommended Intake Limit. Check the recalls section below for full details and affected products.

Active Recalls

Class II March 26, 2025

CGMP Deviations; detection of Nitrosamine Drug Substance-Related Impurities (NDSRI), N-nitroso-desmethyl-diphenhydramine (n-dph), above the FDA Recommended Intake Limit

Chattem Inc

Class II March 4, 2025

CGMP Deviations: Nitrosamine Drug Substance Related Issue impurity above the daily acceptable intake limit defined by the Food and Drug Administration.

Chattem Inc

Class III December 12, 2024

Labeling: Not Elsewhere Classified: Tablets/Capsules imprinted with wrong ID.

Akron Pharma, Inc.

Class III December 12, 2024

Labeling: Not Elsewhere Classified: Tablets/Capsules imprinted with wrong ID.

Akron Pharma, Inc.

Class II June 23, 2022

CGMP Deviations: product held outside appropriate storage temperature conditions.

Family Dollar Stores, Llc.

Class II May 29, 2013

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.

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Medication Guides

Related Health & Safety Data

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 44,288 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

All federal data sources used on this page