Reviewed on 6/27/2022

What Is Diphenhydramine and How Does It Work?

Diphenhydramine is a prescription medication used to treat the symptoms of Allergic Reaction, Insomnia, Cough, Motion Sickness, and Parkinsonism.

  • Diphenhydramine is available under the following different brand names: Benadryl, Benadryl Allergy Dye-Free LiquiGels, Children’s Benadryl Allergy, Children’s Triaminic Thin Strips Allergy, Alka-Seltzer Plus Allergy, Nytol, PediaCare Children’s Allergy, Simply Sleep, Sominex, QlearQuil Nighttime Allergy Relief, Tranquil Nighttime Sleep Aid, Unisome SleepGels, Unisom SleepMelts, ZzzQuil

What Are Side Effects Associated with Using Diphenhydramine?

Common side effects of Diphenhydramine include:

  • drowsiness, 
  • dry eyes, 
  • blurry vision, 
  • dry mouth, nose, or throat,
  • decreased urination, 
  • constipation, 
  • feeling restless or excited, and
  • day-time drowsiness or “hangover” feeling after night-time use

Serious side effects of Diphenhydramine include:

  • hives, 
  • difficulty breathing, 
  • swelling of the face, lips, tongue, or throat, 
  • severe drowsiness, and
  • painful or difficulty urinating

Rare side effects of Diphenhydramine include:

  • none

Seek medical care or call 911 at once if you have the following serious side effects:

  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; sudden dizziness, lightheartedness, or passing out.
This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

What Are Dosages of Diphenhydramine?

Adult and Pediatric dosage

Oral liquid

  • 12.5mg/5ml (Benadryl Allergy Children, PediaCare Children’s Allergy, Allergy Relief Children)
  • 50/30mL (ZzzQuil)


  • 12.5 mg/5mL (Altaryl)


  • 12.5 mg/5mL (Altaryl, Quenalin, Silphen Cough)


  • 25mg (Benadryl, Nytol, Simply Sleep, Sominex, Simply Allergy, Tetra-Formula Nighttime Sleep)
  • 50mg (Alter-Dryl, Nytol Maximum Strength)


  • 25mg (Benadryl Allergy Dye-Free Allergy, Anti-Hist Allergy, Allergy Relief, Diphenhist, Geri-Dryl)
  • 50mg (Banophen, Pharbedryl)

Tablet, chewable

  • 12.5mg (Benadryl Allergy Children)

Tablet, dispersible 

  • 25mg (Unisom SleepMelts)


Injectable solution

  • 50mg/mL

Allergic Reaction

Adult dosage

  • 25-50 mg orally every 6-8 hours; not to exceed 300 mg/day
  • 10-50 mg (no more than 100 mg) IV/IM every 4-6 hours; not to exceed 400 mg/day

Pediatric dosage

  • Children 2-6 years: 6.25 mg every 4-6 hours; not to exceed 37.5 mg/day
  • Children 6-12 years: 12.5-25 mg orally every 4-6 hours; not to exceed 150 mg/day
  • Children older than 12 years: 25-50 mg orally every 4-6 hours; not to exceed 300 mg/day


Adult dosage

  • 50 mg orally 30 minutes before bedtime

Occasional Insomnia

Pediatric dosage

  • Children older than 12 years of age: 50 mg orally 30 minutes before bedtime


Adult dosage

  • 25-50 mg orally every 4 hours as needed (syrup preferred); not to exceed 150 mg/day

Pediatric dosage

  • Children older than 12 years of age: 25-50 mg orally every 4-6 hours; not to exceed 300 mg/day

Motion Sickness

Adult dosage

  • Treatment or prophylaxis: 25-50 mg orally every 6-8 hours
  • Alternative, 10-50 mg/dose for treatment; may use up to 100 mg if needed; not to exceed 400 mg

Pediatric dosage

  • Administer 30 minutes before motion
  • 12.5-25 mg orally every 6-8 hours or 150 mg/m2; not to exceed 300 mg/day


  • 25 mg orally every 8 hours initially, then 50 mg orally every 6 hours; not to exceed 300 mg/day
  • Alternatively, 1-50 mg IV at a rate not to exceed 25 mg/min; not to exceed 400 mg/day; may also administer 100 mg IM required

Dosage Considerations – Should be Given as Follows: 

  • See "Dosages."

What Other Drugs Interact with Diphenhydramine?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them.  Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

  • Diphenhydramine has severe interaction with eliglustat. 
  • Diphenhydramine has serious interactions with at least 11 other drugs.
  • Diphenhydramine has moderate interactions with at least 265 other drugs.
  • Diphenhydramine has minor interactions with at least 34 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use.  Keep a list of all your medications with you, and share this information with your doctor and pharmacist.  Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

What Are Warnings and Precautions for Diphenhydramine?


  • Documented hypersensitivity.
  • Lower respiratory tract disease, such as acute asthma (controversial).
  • Premature infants or neonates.  
  • Nursing mothers. 
  • Use as a local anesthetic.
  • To make a child younger than 6 years sleep when used for self-medication.

Effects of drug abuse

  • None

Short-Term Effects

  • See "What Are Side Effects Associated with Using Diphenhydramine?"

Long-Term Effects

  • See “What Are Side Effects Associated with Using Diphenhydramine?”


  • May cause CNS depression, which can impair driving or operating heavy machinery
  • May potentiate effects of sedatives such as alcohol
  • Use caution in patients with angle-closure glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, thyroid dysfunction
  • Elderly patients: Considered high-risk medication for this age group because it may increase the risk of falls and has a high incidence of anticholinergic effects; may exacerbate existing lower urinary tract conditions or benign prostatic hyperplasia; use in special situations may be appropriate; not recommended for treatment of insomnia, because tolerance develops, and risk of anticholinergic effects increases

Pregnancy and Lactation

  • Pregnancy: Use may be acceptable during pregnancy. 
  • Lactation: Drug enters breast milk; contraindicated.

Health Solutions From Our Sponsors