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Diphenhydramine: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on May 26, 2022.

1. How it works

  • Diphenhydramine is an antihistamine that may be used for the treatment of allergies, motion sickness, to help induce sleep, and to relieve symptoms of Parkinson's Disease.
  • Diphenhydramine treats allergic-type reactions by blocking histamine-1 (H1) receptors. This prevents histamine from having an effect on the airways, blood vessels, and the gastrointestinal tract, reversing symptoms such as bronchoconstriction (narrowing of the airways), rash and itch, and stomach cramps. Diphenhydramine also blocks acetylcholine receptors, sodium channels, and inhibits the reuptake of serotonin, among other effects. These latter effects are responsible for its sedative effects and side effects such as a dry mouth.
  • Diphenhydramine belongs to the class of medicines known as first-generation antihistamines. Diphenhydramine is an antihistamine of the ethanolamine class.

2. Upsides

  • Used to treat the symptoms of allergic-type reactions such as sneezing, itching, watery eyes, and runny nose.
  • May be used for the treatment of allergies, insect bites, hay fever, allergic conjunctivitis, urticaria (hives), and in addition to epinephrine for anaphylactic reactions.
  • May be used to relieve the symptoms of nausea and vomiting associated with motion sickness.
  • Can be used to help people relax or fall asleep.
  • May also be used for elderly people with Parkinson's disease who are unable to tolerate more potent agents.
  • Available as oral tablets/capsules and as a parenteral solution that may be given IV or IM.
  • Available in combination with some other agents, such as acetaminophen 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 that 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 or young children. 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 allergic reactions, relieve motion sickness, as a sleep aid, and to relieve some symptoms of Parkinson's disease. Sedation is a common side effect.

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 nor 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 for, 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 captorpril
  • 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.


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.

Copyright 1996-2023 Revision date: May 25, 2022.