Diphenhydramine Patient Tips

Medically reviewed by Carmen Pope, BPharm. Last updated on July 25, 2025.

1. How it works

• Diphenhydramine is an antihistamine that is used to treat allergic reactions and allergies, motion or travel sickness, as a sleep-aid, and to relieve symptoms of Parkinson's Disease.
• Diphenhydramine blocks H1 histamine receptors and has anticholinergic effects. It relieves symptoms of allergic reactions or allergies by blocking histamine release that causes sneezing, itching, runny nose, and hives. For motion sickness, its anticholinergic properties help reduce nausea and vomiting by affecting the inner ear's balance signals to the brain. As a sleep aid, diphenhydramine causes drowsiness as a side effect of histamine H1 blockade, because it crosses into the brain. It also blocks acetylcholine receptors, and sodium channels, and inhibits the reuptake of serotonin, among other effects. In Parkinson's disease, the anticholinergic effects help restore the balance between dopamine and acetylcholine in the brain, reducing tremors and muscle stiffness, particularly drug-induced movement disorders.
• Diphenhydramine belongs to the drug class called first-generation antihistamines. It is an antihistamine of the ethanolamine class.

2. Upsides

• Used to treat allergy symptoms such as red or watery eyes, sneezing, itching, and a runny nose due to food or other allergens. Used to relieve rashes associated with urticaria and angioedema, allergic reactions due to blood or plasma, or dermatographism. Used in addition to epinephrine for anaphylactic reactions, once the initial symptoms have been controlled.
• May be used to prevent or treat motion sickness.
• Can be used to help people relax or fall asleep as a night-time sleep aid.
• May also be used to relieve symptoms of parkinsonism (including drug-induced) in the elderly unable to tolerate more potent agents; mild cases of parkinsonism (including drug-induced) in other age groups; or for other people with parkinsonism in combination with centrally acting anticholinergic agents.
• Available as oral tablets (25 mg), capsules (25 mg, 50 mg), an oral elixir (12.5 mg / 5 mL), a cream, a spray, and as an injection (50 mg/mL) that may be given IV or IM.
• Available in combination with some other agents, such as acetaminophen, ibuprofen and phenylephrine.
• Oral preparations can be brought over the counter for short-term self-medication.
• Generic diphenhydramine is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Drowsiness and sedation which may impair judgment and affect a person's ability to drive or operate machinery. Alcohol should be avoided because it can make this side effect worse.
• Dizziness, low blood pressure, a headache, rapid heartbeat, disturbed coordination, abdominal discomfort, and thickening of mucus in the airways may also occur.
• May cause a dry mouth, which may increase the risk of dental caries and worsen the symptoms of gastroesophageal reflux disease (GERD) if diphenhydramine is used regularly.
• Not suitable for use in women who are breastfeeding, neonates, or premature infants. Elderly people may be more susceptible to the side effects of sedation, dizziness, and low blood pressure (all of which may increase their risk of falls).
• Overdosage of diphenhydramine has been associated with hallucinations, convulsions, and death. Diphenhydramine toxicity may occur when oral preparations are used at the same time as topical preparations. Symptoms may include dilated pupils, a flushed face, hallucinations, and urinary retention.
• May interact with several other drugs including benzodiazepines, antidepressants, antipsychotics, and alcohol. Has the potential to be misused.
• May not be suitable for some people including those with respiratory diseases such as asthma, narrow-angle glaucoma, peptic ulcer disease, intestinal obstruction, high blood pressure or heart disease, high thyroid levels, an enlarged prostate, or a narrowing of the neck of the bladder.
• Not to be used in neonates or premature infants. Children under the age of 6 should only be given diphenhydramine under a doctor's supervision. The safety and effectiveness of using diphenhydramine as a sleep aid in children under the age of 12 has not been established. There is a risk of overdosage and death if children under the age of 2 are given antihistamines such as diphenhydramine.
• People over the age of 60 may be at increased risk for dizziness, sedation, and low blood pressure.
• Only use during pregnancy if the benefits outweigh the risks. Animal studies have failed to demonstrate a risk to the fetus but there are no adequate and well-controlled studies in humans. Diphenhydramine is secreted into human milk and breastfeeding is not advised because of the potential risks to the feeding infant.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Diphenhydramine is an antihistamine that can be used to treat allergies or allergic reactions, relieve motion sickness, as a sleep aid, and to relieve Parkinson's disease in some people. Sedation is a common side effect and it may cause a dry mouth, which may increase the risk of dental caries and worsen the symptoms of gastroesophageal reflux disease (GERD) if diphenhydramine is used regularly. Available as tablets, capsules, an oral elixir, a cream, a spray, and as an injection that may be given IV or IM.

5. Tips

• Diphenhydramine may be taken with or without food.
• Take exactly as directed. Do not take more than is recommended.
• Do not drive or operate machinery if diphenhydramine makes you drowsy or affects your judgment. Avoid alcohol.
• When using for motion sickness, take diphenhydramine 30 minutes before any exposure to motion. Take subsequent doses before meals or at bedtime for the duration of the exposure.
• Diphenhydramine should not be used as a nighttime sleep aid in children aged less than twelve.
• If you are an adult using diphenhydramine as a sleep aid, see your doctor if your sleeplessness lasts continuously for more than 2 weeks.
• Ensure you maintain good oral hygiene if you are taking diphenhydramine long-term.
• Stand up slowly when going from a sitting or lying down position. Diphenhydramine may cause a drop in blood pressure which may cause symptoms such as dizziness and increase your risk of falls. Remove any fall hazards in your home (such as rugs) and talk to your doctor if you are experiencing severe dizziness every time you stand up.
• Seek urgent medical advice if you experience any symptoms such as agitation, hallucinations, a fast heart rate, dizziness, flushing, muscle tremor or rigidity, nausea, vomiting, or diarrhea.
• Talk to your doctor or pharmacist before taking any other medications while you are taking diphenhydramine. This includes supplements and medicines brought over the counter from a drugstore or grocery store. Do not take oral diphenhydramine at the same time as applying topical diphenhydramine.
• Diphenhydramine is best not taken during pregnancy or while breastfeeding. Talk to your doctor about this if you require more information.

6. Response and effectiveness

• Diphenhydramine is quickly absorbed after oral administration and peak effects are reached within one to four hours. The effects of diphenhydramine last from four to six hours.
• Sedative effects peak 1 to 3 hours after administration of a single dose.
• Antihistamine effects peak 1 to 3 hours and persist for up to 7 hours after administration.
• When used as a night-time sleeping aid, the usual dosage of diphenhydramine is 50mg at bedtime. A lower dosage may be needed in the elderly.

7. Interactions

Medicines that interact with diphenhydramine may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with diphenhydramine. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with diphenhydramine include:

• antiepileptics, such as divalproex sodium, topiramate, or phenytoin
• benzodiazepines, such as diazepam, oxazepam, and temazepam
• bromocriptine
• bupropion
• buspirone
• cannabis
• dextromethorphan
• diuretics, such as furosemide
• duloxetine
• eliglustat
• heart medications, such as amiodarone, atenolol, or captopril
• minoxidil
• monoamine oxidase inhibitors, such as isocarboxazid, selegiline, or tranylcypromine
• opioids, such as oxycodone, morphine, or codeine
• scopolamine
• sedatives, or any medication that causes sedation, such as sleeping pills, muscle relaxants, antipsychotics, or antidepressants
• sodium oxybate
• tamoxifen
• zonisamide
• other medications that contain diphenhydramine, such as creams and gels
• other medications used to treat allergies such as chlorpheniramine.

Alcohol may enhance the sedative effects of diphenhydramine.

Note that this list is not all-inclusive and includes only common medications that may interact with diphenhydramine. You should refer to the prescribing information for diphenhydramine for a complete list of interactions.

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Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use diphenhydramine only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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