This NHS content is written for people in England. Medicine names, availability, prescribing and services may differ in other countries.
Cautions with other medicines
Some medicines can affect the way diphenhydramine works, and increase the chances of you having side effects.
Check with your pharmacist or doctor if you're taking any other medicines, including:
- antidepressants, such as venlafaxine, tricyclic antidepressants (such as amitriptyline) or monoamine oxidase inhibitors (such as phenelzine), or if you have stopped taking these within the past 2 weeks
- any medicines to treat anxiety (such as diazepam) or to help you sleep better
- metoprolol, a heart medicine
- any other antihistamines
- any other medicine that makes you drowsy, gives you a dry mouth, or makes it difficult for you to pee – taking diphenhydramine might make these side effects worse
These are not all the medicines that may cause problems if you take them with diphenhydramine. For a full list, see the leaflet inside your medicine packet.
Taking diphenhydramine with painkillers
You can take diphenhydramine together with painkillers such as paracetamol or ibuprofen.
But if you're taking a cough or cold remedy containing diphenhydramine, check carefully what the other ingredients are. This is because some diphenhydramine products already contain a painkiller. Do not take extra painkillers if they do, as there's a risk of overdose.
Speak to your pharmacist if you're not sure whether a medicine already contains a painkiller.
If you take diphenhydramine with painkillers that contain codeine (such as co-codamol) or other prescription painkillers, you may feel very tired and sleepy. Do not drive, ride a bike or use machinery or tools if this happens to you.
Ask your pharmacist for advice before you take this medicine together with any other painkillers or medicines.
View the original NHS website page ↗. Refreshed 19 August 2026.
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