Diphenhydramine – Side effects, Dosage, and Precautions


Diphenhydramine – perhaps known most commonly as its brand name formulation Benadryl – is a first-generation H1 receptor antihistamine that is used extensively for the treatment of seasonal allergies, insect bites and stings, and rashes. However, it also has antiemetic, antitussive, hypnotic, and anti-parkinson properties. As histamine receptors exist both peripherally and in the central nervous system, diphenhydramine has been shown to cause sedation due to its competitive antagonism of histamine H1 receptors within the central nervous system. While its use in allergy therapy can sometimes fall out of favor due to its sedative effect, diphenhydramine has been repurposed for use within many non-prescription over-the-counter sleep aids and cough-and-cold medications that have been marketed for “night time” use.

Diphenhydramine is also used in combination with 8-chlorotheophylline as the anti-nausea drug Dimenhydrinate where it is utilized primarily for its antagonism of H1 histamine receptors within the vestibular system.

Diphenhydramine has also been shown to be implicated in a number of neurotransmitter systems that affect behaviour including dopamine, norepinephrine, serotonin, acetylcholine, and opioid. As a result, diphenhydramine is being investigated for its anxiolytic and anti-depressant properties.

Properties and characteristics of Diphenhydramine

Drug class Antihistamines
Brand Names Acetadryl, Advil PM, Aleve PM, Allegra Cooling Relief Anti-itch, Banophen, Benadryl, Benadryl Itch Stopping, Benadryl-D Allergy and Sinus, Calagel, Damylin With Codeine, Dimetapp Nighttime Cold & Congestion, Diphen, Diphenhist, Diphenist, Excedrin PM Triple Action, Goody’s PM, Legatrin PM, Motrin PM, Nytol, Nytol Quickgels, Percogesic Reformulated Jan 2011, Siladryl, Simply Sleep, Sleepinal, Sominex, Triaminic Night Time Cold & Cough, Tylenol PM, Unisom, Unisom Sleep, Vanamine, Wal-dryl, Wal-som (doxylamine), Zzzquil
Synonyms Difenhidramina, Diphenhydramine, Diphenhydraminum
Molecular Formula C17H21NO
Molecular Weight 255.35 g/mol
IUPAC Name 2-benzhydryloxy-N,N-dimethylethanamine
Structural formula of main components
Pure active ingredient Diphenhydramine Hydrochloride
Appearance White crystalline powder
Melting point 168°C
Solubility In water, 3.06X10+3 mg/L at 37 °C
Excretion The metabolites of diphenhydramine are conjugated with glycine and glutamine and excreted in urine.
Storage Keep container tightly closed in a dry and well-ventilated place.
Available Forms Tablet, Capsule, Granule, Injection
Prescription Do not consume without the doctors’ advice

Uses of diphenhydramine

Diphenhydramine (Benadryl) is an antihistamine used for treating allergic reactions. Histamine is released by the body during several types of allergic reactions and—to a lesser extent—during some viral infections, such as the common cold.

When histamine binds to receptors on cells, it stimulates changes within the cells that lead to the release of chemicals that cause sneezing, itching, and increased mucus production. Antihistamines compete with histamine for cell receptors and bind to the receptors without stimulating the cells.

In addition, they prevent histamine from binding and stimulating the cells. Diphenhydramine also blocks the action of acetylcholine (anticholinergic effect) and is used as a sedative because it causes drowsiness.

Diphenhydramine side effects

Get emergency medical help if you have any signs of an allergic reaction to diphenhydramine: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using diphenhydramine and call your doctor at once if you have:

  • Pounding heartbeats or fluttering in your chest;
  • Painful or difficult urination;
  • Little or no urinating;
  • Confusion, feeling like you might pass out; or
  • Tightness in your neck or jaw, uncontrollable movements of your tongue.

Common diphenhydramine side effects may include:

  • Dizziness, drowsiness, loss of coordination;
  • Dry mouth, nose, or throat;
  • Constipation, upset stomach;
  • Dry eyes, blurred vision; or
  • Day-time drowsiness or “hangover” feeling after night-time use.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

Mechanism of action

Diphenhydramine predominantly works via the antagonism of H1 (Histamine 1) receptors. Such H1 receptors are located on respiratory smooth muscles, vascular endothelial cells, the gastrointestinal tract (GIT), cardiac tissue, immune cells, the uterus, and the central nervous system (CNS) neurons. When the H1 receptor is stimulated in these tissues it produces a variety of actions including increased vascular permeability, promotion of vasodilation causing flushing, decreased atrioventricular (AV) node conduction time, stimulation of sensory nerves of airways producing coughing, smooth muscle contraction of bronchi and the GIT, and eosinophilic chemotaxis that promotes the allergic immune response.

Ultimately, diphenhydramine functions as an inverse agonist at H1 receptors, and subsequently reverses effects of histamine on capillaries, reducing allergic reaction symptoms. Moreover, since diphenhydramine is a first-generation antihistamine, it readily crosses the blood-brain barrier and inversely agonizes the H1 CNS receptors, resulting in drowsiness, and suppressing the medullary cough center.

Furthermore, H1 receptors are similar to muscarinic receptors. Consequently, diphenhydramine also acts as an antimuscarinic. It does so by behaving as a competitive antagonist of muscarinic acetylcholine receptors, resulting in its use as an antiparkinson medication.

Lastly, diphenhydramine has also demonstrated activity as an intracellular sodium channel blocker, resulting in possible local anesthetic properties.

What may interact with this medication?

Do not take this medication with any of the following:

  • MAOIs like Carbex, Eldepryl, Marplan, Nardil, and Parnate

This medication may also interact with the following:

  • Alcohol
  • Barbiturates, like phenobarbital
  • Medications for bladder spasm like oxybutynin, tolterodine
  • Medications for blood pressure
  • Medications for depression, anxiety, or psychotic disturbances
  • Medications for movement abnormalities or Parkinson’s disease
  • Medications for sleep
  • Other medications for cold, cough or allergy
  • Some medications for the stomach like chlordiazepoxide, dicyclomine

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

Diphenhydramine dosage

Your Diphenhydramine dosage will depend on several factors. These include:

  • The type of condition you’re using diphenhydramine to treat
  • Your age
  • The form of diphenhydramine you’re taking

Typically, you should use the smallest dosage that provides the desired effect.

The following information describes the most commonly used or recommended dosages. If you’re unsure what dosage to take, ask your doctor or pharmacist.

Dosage for hay fever or allergies

  • Typical dosage for adults: 25 to 50 milligrams (mg), every 4 to 6 hours.

Dosage for symptoms of the common cold (such as runny nose or sneezing)

  • Typical dosage for adults: 25 to 50 mg, every 4 to 6 hours.

Dosage for pain and itchy skin from hives, insect bites, and other causes

  • Typical dosage for adults: An application of diphenhydramine cream, gel, or spray to the affected area up to three to four times daily.

Children’s dosage

  • For hay fever or allergies:
    • Children ages 12 years and older: 25 to 50 mg, every 4 to 6 hours.
    • Children 6 to 11 years: 12.5 to 25 mg, every 4 to 6 hours.
    • Children under 6 years: Use only under the direction of a doctor.
  • For symptoms of the common cold (such as runny nose or sneezing):
    • Children ages 12 years and older: 25 to 50 mg, every 4 to 6 hours.
    • Children 6 to 11 years: 12.5 to 25 mg, every 4 to 6 hours.
    • Children under 6 years: Use only under the direction of a doctor.
  • For pain and itchy skin from hives, insect bites, and other causes:
    • Children ages 2 years and older: Apply diphenhydramine cream, gel, or spray to the affected area up to three to four times daily.
    • Children under 2 years: Use only under the direction of a doctor.

Dosage for babies

Over-the-counter oral Benadryl products aren’t approved for use in children under 6 years. Topical Benadryl products that aren’t approved for use in children under 2 years.

Before giving Benadryl to a baby, talk with your doctor. Your doctor may want to evaluate the baby’s symptoms. Your doctor can also recommend the most appropriate dosage of Benadryl to treat a baby if necessary.

Maximum dosage

Oral Benadryl products should not be taken more than six times each day. For adults and children over 12 years of age, the maximum dosage is 300 mg each day. For children ages 6 to 12 years, the maximum is 150 mg each day.

Adults or children should not apply Benadryl products, such as the cream, gel, and spray, to their skin more than four times per day.

Diphenhydramine or Benadryl overdose

Taking too much Benadryl can increase your risk of side effects. Do not use more Benadryl than your recommended dosage.

Overdose symptoms

Symptoms of an overdose in adults and children can include:

  • Involuntary movements
  • Blurred vision
  • Decreased sweating
  • Restlessness
  • Nervousness and anxiety
  • Confusion
  • Hallucinations
  • Heart arrhythmia
  • Difficulty breathing
  • Seizure
  • Coma
  • Death

If you think you’ve taken too much of this drug, call your doctor or seek guidance from Poison Control Centers. However, if your symptoms are severe, call to the nearest emergency room right away.


When taking diphenhydramine, use caution driving, operating machinery, or performing other hazardous activities. Diphenhydramine may cause dizziness or drowsiness. If you experience dizziness or drowsiness, avoid these activities.

Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while taking diphenhydramine.

Do not give this medication to a child younger than 2 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children.

You should not use diphenhydramine to make a child sleepy.

Before taking this medicine

You should not use diphenhydramine if you are allergic to it.

Ask a doctor or pharmacist if it is safe for you to take diphenhydramine if you have other medical conditions, especially:

  • Blockage in your digestive tract (stomach or intestines);
  • Bladder obstruction or other urination problems;
  • A colostomy or ileostomy;
  • Liver or kidney disease;
  • Asthma, chronic obstructive pulmonary disease (COPD), or other breathing disorder;
  • Cough with mucus, or cough caused by smoking, emphysema, or chronic bronchitis;
  • Heart disease, low blood pressure;
  • Glaucoma;
  • A thyroid disorder; or
  • If you take potassium (Cytra, Epiklor, K-Lyte, K-Phos, Kaon, Klor-Con, Polycitra, Urocit-K).

It is not known whether diphenhydramine will harm an unborn baby. Ask a doctor before using this medicine if you are pregnant.

Diphenhydramine can pass into breast milk and may harm a nursing baby. Antihistamines may also slow breast milk production. Ask a doctor before using this medicine if you are breast-feeding.

Check Also

Fexofenadine – Dosage

Background Fexofenadine is an over-the-counter second-generation antihistamine used in the treatment of various allergic symptoms. …

Leave a Reply

Your email address will not be published. Required fields are marked *