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Diphenhydramine (Benadryl) - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

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Diphenhydramine (Benadryl) - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

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Diphenhydramine (Benadryl) is a drug used to relieve symptoms of runny nose, insomnia, itchy eyes, nose or throat, motion sickness, sneezing, sunburn, insect bites, etc. Learn about its uses, dosage, drug warnings, side effects, precautions, drug interactions, etc.

Medically reviewed by

Dr. Mohammad Rajja

Published At March 3, 2022
Reviewed AtOctober 12, 2022


Diphenhydramine (Benadryl) is an over-the-counter (OTC) medicine that belongs to the antihistamine class of drugs and helps to relieve symptoms of seasonal allergies, common cold, hives, insect bites, runny nose, itchiness, watery eyes, scrapes, etc. This drug is available in systemic and topical forms. They are oral tablets, chewable tablets, liquid-filled capsules (liquid-gels), oral liquid solution, topical cream, topical gel, topical spray, and topical stick.

Diphenhydramine (Benadryl) is effective against itchy skin from hives and is often considered the first choice of treatment for hives. Although the effectiveness of this drug for reducing the symptoms of seasonal allergies is high, Benadryl is not often used for this purpose because of its known side effect, sleepiness.


  • Systemic Diphenhydramine (Benadryl)-

This tablet contains,

a) Active Ingredient: Diphenhydramine HCl.

b) Inactive Ingredients:

  • Candelilla wax.

  • Titanium dioxide.

  • Crospovidone.

  • Polyethylene glycol.

  • Hypromellose.

  • Microcrystalline cellulose.

  • Providone.

  • Colloidal silicon dioxide.

  • Stearic acid.

  • Talc.

  • Pregelatinized starch.

Topical Diphenhydramine (Benadryl)-

This cream contains

a) Active Ingredient:

  • Diphenhydramine HCl.

  • Zinc acetate (skin protectant).

b) Inactive Ingredients:

  • Cetyl alcohol.

  • Diazolidinyl urea.

  • Methylparaben.

  • Polyethylene glycol monostearate.

  • Propylene glycol.

  • Propylparaben.

  • Purified water.

Drug Group:

Diphenhydramine (Benadryl) belongs to the class of drugs called antihistamines. Antihistamines are drugs that block the actions of histamine, which causes allergic reactions to the body.

What Is Diphenhydramine (Benadryl) Used For?

A. Systemic Diphenhydramine (Benadryl):

The uses of systemic Diphenhydramine (Benadryl) are as follows,

1. This drug helps to treat symptoms caused by allergies or hay fever. The following are the symptoms of hay fever:

2. This drug temporarily relieves the symptoms caused by the common cold. They are

  • Runny nose.

  • Sneezing.

3. Fights with urticaria (also called hives) - Helps reduce the signs and symptoms of,

4. Physical Urticaria - A condition in which allergic skin rashes (red allergic skin lesions and pruritus) are produced by,

  • Heat exposure.

  • Cold exposure.

  • Contact with chemicals.

  • Contact with plants.

5. Allergic Rhinitis - It is used in allergic rhinitis and helps to relieve the symptoms associated with seasonal and perennial allergic rhinitis in adults and children above 12 years of age.

6. It reduces the symptoms of acute allergic reactions to drugs and foods.

7. Diphenhydramine (Benadryl) antihistamine is also available in combination with Pseudoephedrine which is used to treat allergies, stuffy nose, watery eyes, sneezing, cough, etc., in patients above 12 years of age.

8. It also helps to prevent or treat insomnia and motion sickness.

9. This drug is beneficial to control abnormal movements in people with early-stage Parkinson’s disease.

10. This drug helps prevent and treat dizziness, nausea, and vomiting caused by motion sickness.

11. It is used to relax the body and helps to fall asleep.

12. Extrapyramidal Reactions - It helps with drug-induced movement disorders caused by antipsychotics and other drugs.

B. Topical Diphenhydramine (Benadryl):

The uses of topical Diphenhydramine (Benadryl) are as follows,

1. Itching.

2. Minor burns.

3. Sunburn.

4. Minor cuts.

5. Insect bites.

6. Minor skin irritations.

7. Rashes caused by,

  • Poison ivy.
  • Poison oak.
  • Poison sumac.

8. Dry skin.

9. Minor scrapes.

10. Discharge from the skin.

How Does Diphenhydramine (Benadryl) Work?

Diphenhydramine (Benadryl) belongs to the antihistamine class of drugs that acts as an inverse agonist at histamine-1 (H-1) receptors. These H-1 receptors are located on,

  • Gastrointestinal tract.

  • Cardiac tissue.

  • Respiratory tract.

  • Uterus.

  • Central nervous system.

  • Vascular endothelial cells.

  • Immune cells.

As this drug works on these receptors, it reverses the actions of histamine on capillaries, thus reducing the allergic reactions and their symptoms. Also, Diphenhydramine (Benadryl) belongs to first-generation antihistamines. So, it crosses the blood-brain barrier and acts on the central nervous system, that is, the CNS receptors, resulting in drowsiness.

Onset Of Action:

  • Systemic - Diphenhydramine (Benadryl) has 40 to 60% of oral bioavailability, and it is quickly absorbed orally, showing its maximum activity within an hour. Diphenhydramine (Benadryl) is metabolized in the liver and excreted via feces (6%) and urine (94%). The duration of action is 4 to 6 hours and reaches its peak plasma concentration after 2 to 3 hours of drug intake.

  • Topical - Normally, the topical application of antihistamines starts working within 90 minutes, and the duration of action is less than 180 minutes. They are available in cream forms, gel, spray forms, etc.

Expiry Date:

Avoid taking this medicine after it expires. Diphenhydramine (Benadryl) does not work and may lead to serious side effects when used beyond the expiry date. So before taking medicine, verify the expiry date printed on the back of the pack or ask your pharmacist or doctor in case of any doubts.

What Is the Dosage and Administration of Diphenhydramine (Benadryl)?

The dosage and administration of Diphenhydramine (Benadryl) depend on

  • The Age of the patient.

  • Medical condition.

  • Response to treatment.

1. Systemic Diphenhydramine:

Usual Dosage for Adults

Usual Dosage for Adults

Usual Dosage for Children

Usual Dosage for Children

2. Topical Diphenhydramine:

Preparations and Dosages

Preparations and Dosages

How to Use Diphenhydramine (Benadryl)?

Systemic Diphenhydramine (Benadryl):

  1. Take the tablet, disintegrating tablet, or liquid form of this medicine with or without food. When the doctor has prescribed the medicine, you should take it as directed by the doctor.

  2. You should read all directions on the package label before using this medicine. When you have any doubts or questions, consult your doctor or pharmacist.

  3. On taking the liquid form of this medicine, you should shake the bottle before usage and measure the dose carefully using a dosing syringe or medicine cup or a special measuring device. Avoid using household spoons because you may not get the required dosage.

  4. While taking a disintegrating tablet, you should not immediately swallow the disintegrating tablet; instead, you should allow the disintegrating tablet to dissolve on the tongue before swallowing with or without water.

  5. In terms of chewable tablets, you should not immediately swallow; instead, they should be chewed completely before swallowing.

  6. Always read the dosing instructions before using any product because the dosage of Diphenhydramine may be different for each product.

  7. To prevent motion sickness, you should take the dose 30 minutes before starting your trip. Also, to help with sleep, take medicine 30 minutes before bed.

Topical Diphenhydramine (Benadryl):

  1. Diphenhydramine (Benadryl) should be used only on the skin.

  2. Follow the instructions given by the doctor before usage, and if you are self-treating, you should follow all directions given on the product label.

  3. If you have any doubts, kindly ask the doctor or pharmacist before using them.

  4. Before applying the drug, you should clean the affected area with mild soap and clean water. Pat the area dry and apply on the affected area as directed and should not exceed more than 3 to 4 times a day.

  5. Wash your hands immediately after using the drug, and do not use this medicine for large areas of the body or more than recommended times. This will not cure the condition faster; instead, it improves the chances of risk.

  6. Also, make sure th product does not enter the eyes, ears, nose, or mouth. If it gets in these areas unknowingly, rinse the area or wipe it right away with water.

Missed Dose:

It is important to take the missed dose as soon as you remember it, but if it is almost time for the next dose, you can skip the missed dose and start continuing with the regular dosing schedule. To compensate for a missed one, do not take a double dose.

What Are the Drug Warnings and Precautions?

General precautions for Diphenhydramine (Benadryl):

  1. Before using Diphenhydramine (Benadryl), inform your doctor or pharmacist if you have been allergic to this medicine or have experienced any other allergies because this drug contains inactive ingredients, which may cause allergic reactions or any other problems. So, it is always better to speak to the doctor or pharmacist to know more information.

  2. Before any surgery, tell your doctor or dentist about all the prescription, nonprescription and herbal products you use to avoid future complications.

  3. At the time of pregnancy, this medicine should be used when it is absolutely needed, and the risks and benefits of this medicine should be discussed with your doctor before usage.

  4. It is said that this medication passes into breast milk, so consult with your doctor before taking this drug during breastfeeding.

  5. Avoid increasing the dose by yourself or taking this medication more often than directed by the pharmacist or doctor because the dosage depends on age, response to the treatment, and medical condition.

Specific precautions for Systemic Diphenhydramine (Benadryl):

1. Before using Diphenhydramine (Benadryl), you should tell your doctor or pharmacist about your medical history (present and previous), especially of,

  • Breathing problems:

  1. Asthma.

  2. Emphysema.

  • High pressure in the eye.

  • Heart problems.

  • High blood pressure.

  • Liver disease.

  • Seizures.

  • Stomach problems:

  1. Ulcers.

  2. Blockage.

2. Ask your doctor about the product safety because liquid products may contain sugar, and disintegrating tablets may contain aspartame. So, this medicine should be cautiously taken when there is a need to limit or avoid certain substances in your diet, that is when you have diabetes, phenylketonuria (PKU), or any other conditions.

3. Diphenhydramine (Benadryl) causes drowsiness or blurs the vision, so do not drive or use machinery or do not do things that need alertness. Also, avoid alcoholic beverages.

4. Children are more sensitive to the side effects of Diphenhydramine (Benadryl). It causes excitement in young children.

Specific precautions for Topical Diphenhydramine (Benadryl):

  1. Before using Diphenhydramine (Benadryl), you should tell your doctor or pharmacist about your medical history (present and previous), especially self-treating chickenpox and measles.

  2. There is a possibility that this medication could be absorbed into the blood, so children who use this medicine for an extended period over large areas of the skin, especially on the damaged areas of the skin, may be at higher risk.

  3. Also, people are at high risk if they use other diphenhydramine products, such as those taken by mouth or applied on the skin.

  4. Immediately stop using this drug and seek a doctor right away if any of the following side effects persist. They are,

  • Enlarged pupils.

  • Face flushing.

  • Mood changes:

  • Hallucination.

  • Unusual excitement.

  • Confusion.

  • Difficulty in walking.

  • Difficulty in urinating.

What Are the Side Effects of Diphenhydramine (Benadryl)?

1. Systemic Diphenhydramine-

  • Common Side Effects:

The following are the common side effects of systemic Diphenhydramine (Benadryl), and you should seek a doctor if it worsens and persists for a longer time.

  • Dizziness.

  • Day-time drowsiness.

  • Dry nose.

  • Drowsiness.

  • Loss of coordination.

  • Dry mouth and throat.

  • Stomach upset.

  • Constipation.

  • Dry eyes.

  • Blurred vision.

Serious Side Effects:

Systemic Diphenhydramine (Benadryl) can cause serious side effects, and when you experience any of the following side effects, stop the drug and get emergency medical help.

  • Seizures.

  • Pounding heartbeats.

  • Painful urination.

  • Tightness of the jaw.

  • Little or no urination.

  • Mood changes.

  • Uncontrollable movements of the tongue.

  • Confusion.

  • Lightheadedness.

  • Tightness in the neck.

  • Restlessness.

2.Topical Diphenhydramine-

  • Common Side Effects:

The following are the common side effects of topical Diphenhydramine (Benadryl). You should seek a doctor if it worsens and persists for a longer time.

  • Skin rash.

  • Hives.

  • Skin sensitivity to sunlight.

Serious Side Effects:

Topical Diphenhydramine (Benadryl) does not cause serious side effects but reach a doctor if you experience any of the following symptoms.

  • Rashes.

  • Swelling of the tongue and throat.

  • Itching.

  • Swelling of the face.

  • Trouble breathing.

  • Abnormal sensations of the skin.

What Are the Drug Interactions of Diphenhydramine (Benadryl)?

1. Drug interactions may change the mechanism and effectiveness of the drug; also, they increase the risk of severe side effects. So, it is better to inform your doctor about all the prescription, nonprescription, and herbal drugs you are taking.

2. Do not stop or change the drug dosage by yourself; always ask your doctor's approval before changing the drug dosage.

3. Always read the labels of all medicines you are taking, such as allergy or cough-and-cold products, as they can contain ingredients that cause drowsiness.

4. Ask for any doubts to your doctor or pharmacist about using the products safely.

5. The topical Diphenhydramine has no listed severe, moderate, or mild interactions with other drugs.

6. Diphenhydramine is known to interfere with certain laboratory tests, such as skin allergy testing, so there is a high possibility for false test results. So, tell your laboratory personnel and your doctor about the drug you take.

7. Some of the products interact with Diphenhydramine (Benadryl). Other antihistamines applied to the skin have interaction with Diphenhydramine. Diphenhydramine cream, Diphenhydramine ointment, and Diphenhydramine spray should not be used as they can also produce interactions.

8. Always inform the doctor or pharmacist about the other products you are taking that cause drowsiness. They are

a. Opioid pain relievers:

  • Codeine.

  • Hydrocodone.

b. Alcohol.

c. Marijuana.

d. Drugs for sleep and anxiety:

  • Alprazolam.

  • Lorazepam.

  • Zolpidem.

e. Muscle relaxants:

  • Carisoprodol.

  • Cyclobenzaprine.

f .Other antihistamines:

  • Chlorpheniramine.

  • Cetirizine.

9. Avoid using any other diphenhydramine product applied to the skin or taken by mouth because it can increase the risk of side effects.

10. Always keep a list of all the products you are taking and share it with your doctor or pharmacist to reduce the risk of severe drug interactions.

What Are the Common Brand or Trade Names of Diphenhydramine?

The common brand names of Diphenhydramine are

Systemic Diphenhydramine:

  • Benadryl.

  • Allergy Relief.

  • Banophen.

  • Allergy Relief Children's.

  • Aler-Dryl.

  • Benadryl Allergy.

  • ZzzQuil.

  • Genahist.

  • Aurodryl Allergy Children's.

  • Sominex.

  • Unisom.

  • Allergy Children's.

  • Anti-Hist Allergy.

Topical Diphenhydramine:

  • Benadryl Extra Strength Itch Stopping Gel.

  • Dermamycin.

  • Banophen M-S.

  • Itch Relief.

  • Benadryl Itch Stopping.

  • Aller-Dryl.

  • Banophen Anti-Itch.

  • Benadryl Extra Strength Itch Stopping.

  • Diphenhydramine-D.

Frequently Asked Questions


Is Benadryl the Same as Diphenhydramine?

Benadryl is the trade name for Diphenhydramine. Diphenhydramine (Benadryl) is an over-the-counter (OTC) medication that belongs to the antihistamine drug class and relieves symptoms of seasonal allergies, the common cold, hives, insect bites, runny nose, itchiness, watery eyes, scrapes, etc. There are topical and systemic versions of this medication. These include topical cream, topical gel, topical spray, and topical sticks. In addition, they have liquid-filled capsules (liquid gels), oral liquid solutions, and chewable tablets.


Why Does Diphenhydramine Cause Sleepiness?

Diphenhydramine blocks histamine's effects in the brain, which lessens symptoms. It easily crosses the blood-brain barrier and has an affinity for muscarinic and adrenergic receptors. You may experience drowsiness due to it entering the brain in large quantities


What Is the Best Time to Take Diphenhydramine?

Diphenhydramine is typically taken every four to six hours to treat the symptoms of allergies, colds, and coughs. Diphenhydramine is usually taken 30 minutes before departure and, if necessary, before meals and bedtime to treat motion sickness. Diphenhydramine is taken before bedtime when used to treat insomnia (30 minutes before planned sleep). Diphenhydramine is typically taken four times daily after being taken three times daily to treat abnormal movements


How Much Diphenhydramine Should I Take to Fall Asleep?

Diphenhydramine 50mg is taken before bedtime when used to treat insomnia (30 minutes before planned sleep). The maximum dosage for Diphenhydramine as a sleep aid is 76 mg for Diphenhydramine citrate and 50 mg for Diphenhydramine hydrochloride. It is not advised to use Diphenhydramine as a sleep aid for more than seven to ten nights because you will develop a tolerance to it. The side effects of an overdose of Diphenhydramine can range from dry mouth and sleepiness to coma and even death


How Does Diphenhydramine Affect the Brain?

Diphenhydramine blocks histamine's effects in the brain, which lessens symptoms. It easily crosses the blood-brain barrier and has an affinity for muscarinic and adrenergic receptors. You may experience drowsiness due to it entering the brain in large quantities. Diphenhydramine also inhibits the brain chemical acetylcholine, which is important for attention and short-term memory, so older people who take it may experience confusion. Long-term use of Diphenhydramine can increase a person's risk of developing dementia.


Can Diphenhydramine Raise Blood Pressure?

Diphenhydramine, a first-generation antihistamine that lessens the effects of histamines in your body, does not typically cause increased or high blood pressure. However, the medication can occasionally lower blood pressure or hypotension.  You may also experience other typical side effects such as sleepiness, vertigo, or wobbly gait. You might also find it difficult to focus and have a dry mouth


Is Diphenhydramine a Controlled Substance?

Due to its potentially serious side effects and minimal euphoric effects, Diphenhydramine is not considered to have a high potential for abuse in the United States and is not a controlled substance. If taken regularly in the form of a liquid, tablet, or capsule, the medication used to treat conditions like insomnia, nausea, the common cold, and Parkinson's patients' tremors can become addictive.


Does Diphenhydramine Cause Dementia?

Long-term Diphenhydramine use can increase a person's risk of developing dementia and impair many cognitive processes, including memory. Although rare, older adults or those who have taken the medication for a long time may experience this side effect more frequently. Examples of symptoms are finding the right words to say or having difficulty speaking.


Is Diphenhydramine a Depressant?

Diphenhydramine has both stimulant and depressant effects on the central nervous system, though patients receiving conventional doses rarely experience stimulation, accompanied by agitation, anxiety, and insomnia. Typically, it acts as a CNS depressant and blocks histamine signals. Antihistamine-induced decreases in cognitive and psychomotor function are usually attributed to increased sedative effects.


Is It Safe to Take Diphenhydramine and Ibuprofen Together?

Diphenhydramine is not known to interact with Acetaminophen or Ibuprofen. Combining ibuprofen and Diphenhydramine treats minor aches and pains that interfere with sleep. Additionally, it aids in sleep onset and maintenance. The nonsteroidal anti-inflammatory drug (NSAID) ibuprofen reduces pain, swelling, and inflammation


What Are the Contraindications of Diphenhydramine?

Premature babies and neonates with known Diphenhydramine hypersensitivity.
Lactating mothers.
Pregnancy category B: only apply when necessary.
Diphenhydramine interacts with alcohol and other CNS depressants in a complementary manner (hypnotics, sedatives, tranquilizers).
The anticholinergic effects of antihistamines are prolonged and strengthened by monamine oxidase A inhibitors
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Dr. Mohammad Rajja
Dr. Mohammad Rajja

General Practitioner


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