Diphenhydramine: Formula, Presentation, Indications, Mechanism of Action, Dosage, Side Effects and Interactions

These types of medications can reduce or prevent allergic reactions by counteracting the effects of histamine.

Diphenhydramine belongs to a group of medicines known as antihistamines.

Chemical formula

  • C17H21NO.


This medicine is available as:

Liquid / oral solution: 12.5 mg / 5 ml and 50 mg / 30 ml.

Elixir: 12.5 mg / ml.

Jarabe: 12.5 mg / ml.

Tablets and capsules:  25 mg and 50 mg.


Tableta masticable: 12.5 mg.

Tabletas dispersables: 25 mg.

Injectable solution: 50 mg / ml.

It is also available in creams.


Antihistamines are used primarily to treat symptoms caused by allergies, including watery and itchy eyes, sneezing, runny nose, rashes, and irritations.

The cream form of this medication is also used to relieve the swelling and itching caused by insect bites, poison ivy, poison oak, and some mild cases of sunburn and other minor skin irritations.

Mechanism of action

This medication works by blocking the effects of histamine, a substance released by the body involved in allergies.

It usually starts working after one hour.

Its drying effects on symptoms such as watery eyes and nasal discharge are caused by the blockage of another natural substance produced by the body called acetylcholine.

When it reduces the activity of a chemical messenger in the brain called acetylcholine, it relieves spasms and muscle tremors.


Many factors can affect the dose of medication that should be administered to the patient; among them are:

The patient’s body weight, the presence of other medical conditions, and the treatment with other medications concomitant with diphenhydramine.

The recommended standard doses are:

In adults:

  • From 25 to 50 mg orally every 6 to 8 hours, without exceeding the maximum dose of 300 mg per day.
  • From 10 to 50 mg, with a total dose of 100 mg intravenously or intramuscularly every 4 to 6 hours, without exceeding 400 mg per day.

In children:

  • In children aged 2 to 6 years, a dose of 6.25 mg should be administered every 4 to 6 hours, without exceeding 37.5 mg per day.
  • In children aged 6 to 12 years, a dose of 12.5 to 25 mg orally should be administered every 4 to 6 hours, without exceeding 150 mg per day.
  • Children 12 years and older should be administered a dose of 25 to 50 mg orally every 4 to 6 hours, without exceeding 300 mg per day.


  • 25 mg orally, intravenously, or intramuscularly every 8 to 12 hours should be used only for emergency allergic reactions at the minimum effective dose.
  • Non-anticholinergic antihistamines should be considered first to treat the allergic reaction (Beers criteria). The use of diphenhydramine in the acute treatment of severe allergic reactions may be appropriate.


  • The recommended dose is 50 mg orally, 30 minutes before bedtime.
  • For children under 12 years, the dose of 1 mg per kg 30 minutes before bedtime should not exceed 50 mg per day.
  • For children 12 years of age or older, the recommended dose is 50 mg orally 30 minutes before bedtime.


  • From 25 to 50 mg orally, every 4 hours as needed (syrup), without exceeding 150 mg per day.
  • For children under 12 years, safety and effectiveness have not been established.
  • For children 12 years old or older, the recommended dose is 25 to 50 mg orally every 4 to 6 hours, without exceeding 300 mg per day.


  • The recommended dose is 25 mg orally every 8 to 12 hours. However, its use in the elderly should be avoided if possible.


  • Dosage of 25 mg orally every 8 hours initially, then 50 mg orally every 6 hours, without exceeding 300 mg per day.
  • Alternatively, from 10 to 50 mg intravenously at a rate not exceeding 25 mg per minute, the daily dose should not exceed 400 mg; 100 mg may also be administered intramuscularly.

Dystonic reaction:

  • 50 mg intravenously and intramuscularly can be repeated in 20 to 30 minutes if necessary.


Apply a thin layer of cream 3 or 4 times a day on the affected area for adults and children two years and older.

If the skin condition worsens or persists for more than seven days, do not continue this medication without consulting your doctor or pharmacist.

Side effects

The following side effects have been reported with the application of diphenhydramine treatment, many of these side effects can be controlled, and some disappear over time.

Among the side effects, we have:

  • Constipation.
  • The throat and dry nasal mucosa.
  • Drowsiness.
  • Dizziness
  • The excitement (especially in children).
  • Nausea
  • Nervousness.
  • Thickening of mucus.
  • Sedation.
  • Confusion.
  • They have decreased cognitive function in geriatric patients.
  • Thick bronchial sputum.
  • Low count of white blood cells and blood platelets.
  • The presence of seizures.
  • Low blood pressure
  • Restlessness.
  • Blurry vision.
  • Irregular and rapid heartbeat (palpitations).
  • The sensation of rotation (vertigo).
  • Menstrual irregularities.
  • Euphoria.
  • Loss of appetite
  • Urinary retention.
  • Inflammation of the nerves.
  • Double vision.
  • We are ringing in the ears (tinnitus).
  • Presence of difficult or painful urination.

The medication should be discontinued, and the doctor should be consulted immediately in case of symptoms of a severe allergic reaction such as:

Urticaria, difficulty breathing, swelling of the face, mouth, tongue or throat.

Warnings and contraindications

You should not use this medication if you are allergic to diphenhydramine or any other ingredient in the formula.

Topical cream should not be used for diseases such as chickenpox, measles, or large areas of the skin.

If the condition worsens or lasts more than seven days, you should see a doctor.

With the administration of the topical cream, it is not advisable to administer it with other medicines that contain diphenhydramine as tablets, capsules, and liquids.

In the short term, depression of the central nervous system can cause drowsiness or reduced alertness, which can affect the driving of vehicles or the operation of heavy machinery.

Therefore, it is recommended not to do so until you have determined that this medication does not affect your ability to perform these tasks safely.

It can also increase the effects of sedatives like alcohol.

In elderly patients, this medication is considered high risk for this age group since it can increase the risk of falls and has a high incidence of anticholinergic effects; it can also exacerbate existing urinary problems and prostatic hyperplasia.

Diphenhydramine is not recommended for the treatment of insomnia in elderly patients as tolerance develops.

In elderly patients, this medication is more likely to cause dizziness, drowsiness, and low blood pressure.

Caution should be exercised in patients with angle-closure glaucoma, prostatic hypertrophy, peptic ulcer, pyloroduodenal obstruction, and thyroid dysfunction.

The use of diphenhydramine during pregnancy is not recommended, studies in animals have shown no risk, but no studies have been conducted in humans.

The doctor can recommend treatment when the benefits outweigh the risks to the fetus.

In case the patient becomes pregnant, the doctor should be contacted immediately.

The safety of using this medication during breastfeeding has not been established.

In cases where nursing mothers take this medication, the baby can be affected since the drug is excreted in breast milk and can induce a paradoxical stimulation of the central nervous system in newborn babies or convulsions in the case of premature babies.

This medicine can also produce inhibition of breastfeeding; you should consult your doctor about whether you should continue breastfeeding.

It should not be administered to children under two years of age since its safety and effectiveness in using this drug have not been established yet.


Interactions have been reported between diphenhydramine and any of the following medications:

  1. Anticholinergics such as benztropine and oxybutynin.
  2. Antihistamines such as brompheniramine and chlorpheniramine.
  3. Barbiturates such as phenobarbital and butalbital.
  4. Benzodiazepines such as diazepam, lorazepam and oxazepam.
  5. Muscle relaxants such as cyclobenzaprine.
  6. Opioid medications such as codeine or morphine.
  7. Other drugs that cause drowsiness include chlorpromazine, gabapentin, loxapine,  mirtazapine, quetiapine, zopiclone, and droperidol.
  8. As well as the concomitant use of diphenhydramine with alcoholic beverages.