Diphenhydramine Uses, Dosage, Side Effects, Food Interaction and all others data.

Diphenhydramine is an antihistamine with anticholinergic and sedative effects. It competes with histamine for H1-receptor sites on effector cells in the GI tract, blood vessels and respiratory tract.

Diphenhydramine has anti-histaminic (H1-receptor), anti-emetic, anti-vertigo and sedative and hypnotic properties . The anti-histamine action occurs by blocking the spasmogenic and congestive effects of histamine by competing with histamine for H1 receptor sites on effector cells, preventing but not reversing responses mediated by histamine alone . Such receptor sites may be found in the gut, uterus, large blood vessels, bronchial muscles, and elsewhere . Anti-emetic action is by inhibition at the medullary chemoreceptor trigger zone . Anti-vertigo action is by a central antimuscarinic effect on the vestibular apparatus and the integrative vomiting center and medullary chemoreceptor trigger zone of the midbrain .

Trade Name Diphenhydramine
Availability Rx and/or OTC
Generic Diphenhydramine
Diphenhydramine Other Names Difenhidramina, Diphenhydramine, Diphenhydraminum
Related Drugs Gocovri, prednisone, ibuprofen, acetaminophen, hydroxyzine, amitriptyline, lorazepam, ondansetron, cetirizine, loratadine
Weight 0/ml, , 75mg + 25mg + 7.5mg/5ml, 10mg/ml
Type Syrup, Oral Solution, Oral Liquid, Oral Powder For Reconstitution, Oral Syrup, Oral Tablet, Oral Suspension, Extended Release, Injection
Formula C17H21NO
Weight Average: 255.3547
Monoisotopic: 255.162314299
Protein binding

Some prescribing information records the protein binding of diphenhydramine as approximately 78% while others have suggested the medication is about 80 to 85% bound to plasma proteins.

Groups Approved, Investigational
Therapeutic Class Sedating Anti-histamine
Manufacturer Nawabsons Laboratories (pvt) Ltd, , Harsen, Dexa Medica, Ferron Par Pharmaceuticals, Ipha Laboratories, Phapros, Bernofarm, Lucas Djaja, Phapros, Meprofarm
Available Country Pakistan, United States, Indonesia
Last Updated: September 19, 2023 at 7:00 am

How Diphenhydramine works

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 .


Diphenhydramine dosage


  • Most allergic conditions: 25-50 mg three times a day with a further 50 mg at night.


  • 1 to 5 years of age: 5 mg i.e., 2.5 ml of elixir 4 times a day
  • More than 6 years of age: 10 mg i.e. 5 ml of elixir 4 times a day

Side Effects

Side effect includes sedation, dizziness, tinnitus, fatigue, ataxia, blurred vision, diplopia, euphoria, and epigastric discomfort.


Overdose is expected to result in effects similar to the adverse effects that are ordinarily associated with the use of diphenhydramine, including drowsiness, hyperpyrexia, and anticholinergic effects, among others . Additional symptoms during overdose may include mydriasis, fever, flushing, agitation, tremor, dystonic reactions, hallucinations and ECG changes . Large overdose may cause rhabdomyolysis, convulsions, delirium, toxic psychosis, arrhythmias, coma and cardiovascular collapse . Moreover, with higher doses, and particularly in children, symptoms of CNS excitation including hallucinations and convulsions may appear; with massive doses, coma or cardiovascular collapse may follow .

Although diphenhydramine has been in widespread use for many years without ill consequence, it is known to cross the placenta and has been detected in breast milk . This medication should therefore only be used when the potential benefit of treatment to the mother exceeds any possible hazards to the developing fetus or suckling infant .

Pharmacokinetic studies indicate no major differences in the distribution or elimination of diphenhydramine compared to younger adults . Nevertheless, diphenhydramine should be used with caution in the elderly, who are more likely to experience adverse effects . Avoid use in elderly patients with confusion .

The results of a review on the use of diphenhydramine in renal failure suggest that in moderate to severe renal failure, the dose interval should be extended by a period dependent on Glomerular filtration rate (GFR) .

After intravenous administration of 0.8 mg/kg diphenhydramine, a prolonged half-life was noted in patients with chronic liver disease which correlated with the severity of the disease . However, the mean plasma clearance and apparent volume of distribution were not significantly affected .

LD50=500 mg/kg (orally in rats). Considerable overdosage can lead to myocardial infarction (heart attack), serious ventricular dysrhythmias, coma and death.


Caution should be exercised with patients in whom drowsiness is undesirable e.g., drivers, machine operators. Concomitant consumption of alcohol or central nervous system (CNS) depressants will potentiate drowsiness.


Diphenhydramine administration significantly reduces the absorption of the antituberculous agent para-aminosalicyclic acid (PAS) from the gastrointestinal tract. CNS depressants may potentiate the sedative action of Diphenhydramine. Anticholinergic drugs may potentiate Diphenhydramine’s anticholinergic side effects.

Food Interaction

  • Avoid alcohol.
  • Take before a meal. Take 30 minutes before a meal or 30 minutes before departure for motion sickness.

Diphenhydramine Alcohol interaction


Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous.

In addition, the potential for abuse may be increased with the combination.

The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system.

No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load.

However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

Alcohol should generally be avoided during therapy with anticholinergic agents.

Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

Volume of Distribution

Diphenhydramine is widely distributed throughout the body, including the CNS . Following a 50 mg oral dose of diphenhydramine, the volume of distribution is in the range of 3.3 - 6.8 l/kg .

Elimination Route

Diphenhydramine is quickly absorbed after oral administration with maximum activity occurring in approximately one hour . The oral bioavailability of diphenhydramine has been documented in the range of 40% to 60%, and peak plasma concentration occurs about 2 to 3 hours after administration .

Half Life

The elimination half-life ranges from 2.4-9.3 hours in healthy adults . The terminal elimination half-life is prolonged in liver cirrhosis .


Values for plasma clearance of a 50 mg oral dose of diphenhydramine has been documented as lying in the range of 600-1300 ml/min .

Elimination Route

The metabolites of diphenhydramine are conjugated with glycine and glutamine and excreted in urine . Only about 1% of a single dose is excreted unchanged in urine . The medication is ultimately eliminated by the kidneys slowly, mainly as inactive metabolites .

Pregnancy & Breastfeeding use

Category B: There are no adequate and well controlled studies in pregnant women using diphenhydramine hydrochloride. Therefore, diphenhydramine hydrochloride should be used in pregnancy only if clearly needed. Diphenhydramine hydrochloride has been reported to be excreted in breast milk and thus, use of diphenhydramine hydrochloride in lactating mother is not recommended.


Known hypersensitivity to Diphenhydramine Hydrochloride, Ammonium chloride is contra-indicated in presence of impaired hepatic or renal function.

Acute Overdose

Symptoms: Impaired consciousness; psychosis, seizures, antimuscarinic symptoms (e.g. mydriasis, tachycardia, tachyarrhythmias), resp failure, rhabdomyolysis; acute delirium with visual and auditory hallucination (topical).

Management: Supportive and symptomatic treatment. Convulsions and marked CNS stimulation may be treated with IV diazepam.

Storage Condition

Store between 15-30° C. Protect from moisture.

Innovators Monograph

You find simplified version here Diphenhydramine

Diphenhydramine contains Diphenhydramine see full prescribing information from innovator Diphenhydramine Monograph, Diphenhydramine MSDS, Diphenhydramine FDA label


What is Diphenhydramine used for?

Diphenhydramine is an antihistamine used to relieve symptoms of allergy, hay fever, and the common cold. These symptoms include rash, itching, watery eyes, itchy eyes/nose/throat, cough, runny nose, and sneezing. It is also used to prevent and treat nausea, vomiting and dizziness caused by motion sickness.

How safe is Diphenhydramine?

The U.S. Food and Drug Administration is warning that taking higher than recommended doses of the common over-the-counter (OTC) allergy medicine diphenhydramine can lead to serious heart problems, seizures, coma, or even death.

How does Diphenhydramine work?

Diphenhydramine works by blocking the action of histamine, a substance in the body that causes allergic symptoms.

What are the common side effects of Diphenhydramine?

Common side effects of Diphenhydramine are include:

  • dry mouth, nose, and throat
  • drowsiness
  • dizziness
  • nausea
  • vomiting
  • loss of appetite
  • constipation
  • increased chest congestion
  • headache
  • muscle weakness
  • excitement (especially in children)
  • nervousness

Is Diphenhydramine safe during pregnancy?

Diphenhydramine is considered to be safe during pregnancy. Doctors and nurses recommend this OTC medication to help relieve allergy symptoms, even while you're pregnant. Recent studies have found Diphenhydramine to be safe.

Is Diphenhydramine safe during breastfeeding?

Small, occasional doses of Diphenhydramine would not be expected to cause any adverse effects in breastfed infants.

Can I drink alcohol with Diphenhydramine?

Alcohol may increase drowsiness and dizziness while you are taking Diphenhydramine. You should be warned not to exceed recommended dosages and to avoid activities requiring mental alertness. If your doctor prescribes these medications together, you may need a dose adjustment to safely take this combination.

Can I drive after taking Diphenhydramine?

Do not drive or operate machinery if Diphenhydramine makes you drowsy or affects your judgment.

When should be taken of Diphenhydramine?

When Diphenhydramine is used to treat motion sickness, it is usually taken 30 minutes before departure and, if needed, before meals and at bedtime.

How often can I take Diphenhydramine?

Diphenhydramine is usually taken every 4 to 6 hours.

How much Diphenhydramine can I take in a day?

For adults and teens, the Diphenhydramine dosage is 25 to 50 mg every 4 to 6 hours. The maximum amount you should take in one day is 300 mg. Keep in mind, taking higher doses can increase the risk of side effects, including drowsiness.

Is Diphenhydramine bad for my liver?

Despite widespread use over many decades, Diphenhydramine has not been linked to liver test abnormalities or to clinically apparent liver injury. The reason for its safety may relate its short half-life and limited duration of use.

How long does Diphenhydramine take to work?

It normally takes about 30 minutes to work. Common side effects include feeling sleepy, dizzy or unsteady on your feet. You may also have difficulty concentrating and have a dry mouth.

Can I take Diphenhydramine on an empty stomach?

Diphenhydramine may be taken with or without food. Take exactly as directed. Do not take more than is recommended.

How long does Diphenhydramine stay in my system?

A half-life of a drug determines how long it will take for 50% of it to flush out of your system. Depending on the median value that the individual lands on, Diphenhydramine can stay in your system anywhere between 13.2 and 49 hours.

Can Diphenhydramine be taken long-term?

Caution should be exercised for long-term use of Diphenhydramine, an antihistamine and a non-benzodiazepine sedative-hypnotic, because of the association of increased risk for dementia.

How long can I use Diphenhydramine?

Do not use Diphenhydramine for longer than 2 weeks to treat sleep problems, or longer than 7 days to treat cold or allergy symptoms.

Who should not take Diphenhydramine?

If you have increased pressure in the eye, closed angle glaucoma, high blood pressure, stenosing peptic ulcer you should not take Diphenhydramine.

What happen If I suddenly stop taking Diphenhydramine?

Although withdrawal symptoms of Diphenhydramine are minor compared to harder drugs, you may experience cold sweats, nausea, or diarrhea when stopping the drug suddenly.

What happen If I missed Diphenhydramine?

Since Diphenhydramine is used when needed, you may not be on a dosing schedule. If you are on a schedule, use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

What happen if I take too much Diphenhydramine?

Taking more than the normal Diphenhydramine dosage can be harmful. Serious side effects from too much of the Diphenhydramine can include nausea, vomiting, blurred vision, trouble breathing, hallucinations, unconsciousness, and seizures.

Can Diphenhydramine cause heart problems?

Taking too much Diphenhydramine can lead to serious heart problems, seizures, coma, or death.

Can Diphenhydramine cause heart palpitations?

A fast heartbeat is a common side effect of Diphenhydramine. In rare cases, it can become serious.

Can Diphenhydramine damage kidneys?

In general, Diphenhydramine do not cause kidney problems.

*** Taking medicines without doctor's advice can cause long-term problems.