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.

Uses

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

  • Anaphylaxis
  • Insomnia
  • Antitussive (anti-cough)
  • Parkinsonian syndrome including extrapyramidal symptoms
  • Prevention and treatment of motion sickness
  • Cold symptoms

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).

Dosage 

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 dayInsomnia: 50 mg orally once a day at bedtimeMotion sickness: 25 to 50 mg 3 to 4 times a dayAllergic rhinitis: 25 to 50 mg orally every 4 to 6 hours as needed Maximum dose: 300 mg/dayCold symptoms: 25 to 50 mg orally every 4 to 6 hours as needed. Maximum dose: 300 mg/dayPruritus: 25 to 50 mg orally every 4 to 6 hours as needed. Maximum dose: 300 mg/dayUrticaria: 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.

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:

  • Breastfeeding
  • History of hypotension
  • A history of alcoholism or drug abuse
  • Are currently taking benzodiazepines, antidepressants, and/or antipsychotics
  • Have a history of asthma
  • Have a history of narrow-angle glaucoma
  • Have a history of peptic ulcer disease
  • Have an intestinal obstruction
  • Have a history of high blood pressure or heart disease

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.  

  • LexiComp. Diphenhydramine uses.
  • Benadryl. Benadryl dosing guide.
  • 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
  • Benadryl. Diphenhydramine side effects.
  • 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.

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