What to Know About Diphenhydramine

An Antihistamine Drug Commonly Used for Allergic Reactions

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Diphenhydramine is a first-generation antihistamine that blocks the effects of histamine, a chemical created by the immune system. An increase in histamine release generally occurs when your immune system overreacts to allergens, such as pollen, pet dander, or a drug, especially in allergic reactions. Histamine can cause symptoms such as coughing, sneezing, itchy watery eyes, itchy skin, or hives.

Diphenhydramine is a common ingredient that is used in a variety of over-the-counter (OTC) medications that can be used in a variety of forms, including single-ingredient and combination-ingredient products, and as pills, capsules, liquids, and chewable tablets. The most common brand name is Benadryl.

Potential Diphenhydramine Side Effects

Verywell / Katie Kerpel


Diphenhydramine is most commonly used to treat allergic symptoms caused by histamine release. It is also used for the following purposes:

Off-Label Uses

These are uses that are not indicated for medication by the Food and Drug Administration (FDA), but a healthcare provider may recommend using it nonetheless:

  • Angioedema
  • Infusion or transfusion-related reactions
  • Nausea and vomiting
  • Scombroid (histamine) poisoning
  • Urticaria (hives)
  • Acute vertigo

Before Taking

Your medical provider will determine your medication dose and timing. It is important to note that diphenhydramine is an OTC medication, and safe dosing instructions are found on all generic and brands of this medication.

How to take diphenhydramine: 

  • Inform all of your healthcare providers that you are taking this drug.
  • Tell your healthcare provider about all other medications, vitamins, and supplements that you are taking, as some may interact with diphenhydramine.
  • Diphenhydramine can be taken via tablet, liquid, and/or intravenously.
  • Chewable tablets and oral-disintegrating tablets should be chewed well or dissolved completely in the mouth.
  • Diphenhydramine can be taken with or without food.
  • Diphenhydramine is taken as needed, but do not take more than the maximum recommended dose.
  • Take the medication dosage as ordered by your medical provider or as indicated on the packaging.
  • Avoid driving or operating heavy machinery until you are aware of how the medication will affect you.
  • Don't use alcohol when you have diphenhydramine in your system.
  • Talk with your healthcare provider if you are planning to use marijuana.
  • Do not take if you are pregnant or breastfeeding unless directed to do so by your healthcare provider.
  • Do not take other medications containing diphenhydramine.

Other Antihistamines

Diphenhydramine is one of the first-generation antihistamines, which are known to be sedating. Others include brompheniramine, chlorpheniramine, dimenhydrinate, and doxylamine.

Second-generation antihistamines are non-sedating. These include Alavert and Claritin (loratadine), Zyrtec (cetirizine), and Allegra (fexofenadine).


All listed dosages are according to the drug manufacturer. Check your prescription and talk to your healthcare provider to make sure you are taking the right dose for you.

General Adult Dosage Information

These dosages are suggested by the manufacturer:

  • Extrapyramidal reaction: 25 to 50 milligrams (mg) orally 3 to 4 times a day
  • Insomnia: 50 mg orally once a day at bedtime
  • Motion sickness: 25 to 50 mg 3 to 4 times a day
  • Allergic rhinitis: 25 to 50 mg orally every 4 to 6 hours as needed Maximum dose: 300 mg/day
  • Cold symptoms: 25 to 50 mg orally every 4 to 6 hours as needed. Maximum dose: 300 mg/day
  • Pruritus: 25 to 50 mg orally every 4 to 6 hours as needed. Maximum dose: 300 mg/day
  • Urticaria: 25 to 50 mg orally every 4 to 6 hours as needed. Maximum dose: 300 mg/day

Pediatric Dosage Information

There are many formulations of products that contain diphenhydramine for children, but it is important to note the age restrictions and recommended dosages. These are examples.

Children's BENADRYL Allergy Liquid (diphenhydramine hydrochloride 12.5 mg in 5 mL)
Age Dose
Children under 2 years Do not use
Children 2 years to 5 years Do not use unless directed by healthcare provider
Children 6 years to 11 years 5 ml to 10 ml
Children's BENADRYL Allergy Plus Congestion (diphenhydramine hydrochloride 12.5 mg and phenylephrine hydrochloride 5 mg in 5 mL)
Age Dose
Children under 4 years Do not use
Children 4 years to 5 years Do not use unless directed by healthcare provider
Children 6 years to 11 years 5 ml
Adults and children 12 years and over 10 ml
Children's BENADRYL Chewable Tablets (diphenhydramine hydrochloride 12.5 mg)
Age Dose
Children under 2 years Do not use
Children 2 years to 5 years Do not use unless directed by a healthcare provider
Children 6 years to 11 years 1 to 2 chewable tablets
Adults and children 12 years and over 2 to 4 chewable tablets

How To Take and Store

Follow these precautions:

  • Store at room temperature and protected from light.
  • Store in a dry place.
  • Do not refrigerate or freeze.
  • Throw away liquid suspension after eight weeks due to potential instability.
  • Throw away unused or expired medication.

Side Effects

Most side effects associated with this medication are not harmful, but you should tell your healthcare provider about all of your side effects.

Common side effects can include:

  • Sedation/sleepiness
  • Dizziness
  • Epigastric distress (abdominal discomfort)
  • Thickening of secretions
  • Headache
  • Coordination difficulties
  • Dry mouth
  • Vertigo
  • Urticaria
  • Irritability
  • Euphoria

Serious side effects, which should be immediately reported to your healthcare provider, include: 

  • Tremor
  • Convulsions
  • Blurred vision
  • Anaphylactic shock
  • Chest tightness
  • Palpitations (sense of a rapid or throbbing heartbeat)
  • Hallucinations
  • Extrapyramidal effects (tremors, stiffness, spasms, and/or involuntary movements)
  • Pharyngeal edema (severe swelling and tightness in your throat)

Hemolytic anemia and thrombocytopenia are side effects that involve blood cells. Symptoms can include fatigue, weakness, rapid pulse, shortness of breath, bleeding, and/or bruising,

Warnings and Interactions

Diphenhydramine or any medications containing it should not be used by adults age 65 or older unless directed by a healthcare provider.

Diphenhydramine should be used with caution by people to whom any of the following may apply, so check with your healthcare provider before using:

A Word From Verywell

Children and the elderly are more sensitive to the effects of antihistamine, and special precautions should be taken when using these products in these age groups. Antihistamines such as Benadryl or others should never be given to children under 4 years of age. These medications can cause life-threatening side effects. Always read and follow the directions on the labels and consult with your healthcare providers or pharmacists if you have concerns or questions.  

5 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. LexiComp. Diphenhydramine uses.

  2. Benadryl. Benadryl dosing guide.

  3. Palmer RB, Reynolds KM, Banner W, et al. Adverse events associated with diphenhydramine in children, 2008–2015. Clinical Toxicology. 2020;58(2):99-106. doi:10.1080/15563650.2019.1609683

  4. Benadryl. Diphenhydramine side effects.

  5. MedlinePlus. Diphenhydramine.

By Kathleen Gaines, MSN, RN, CBC
Kathleen Gaines, MSN, RN, CBC, is a nurse and health journalist, as well as an adjunct clinical faculty member at hospitals in the Philadelphia area.