Medications That Should Never Be Combined with Benadryl

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Which medications does Benadryl interact with?  

Benadryl is the brand name of the generic medication diphenhydramine, a commonly used over-the-counter antihistamine, effective in relieving sneezing, runny nose, and itchy, watery eyes. However, taking Benadryl with certain other medications can result in potentially dangerous drug interactions. 

The following medications or substances, including others not listed, can have drug interactions with Benadryl. 

Alcohol

Alcohol alone is a CNS depressant; taken together with Benadryl, it can increase the sedating effect of Benadryl, thus worsening drowsiness. So if you drink alcohol while taking Benadryl, you will feel extremely sleepy. 

Drinking alcohol while on Benadryl can also lead to other side effects like dizziness, confusion, and slowed breathing rate. These effects can impair your alertness and ability to focus, putting you at risk of accidents.

Blood pressure medications

There is no known drug interaction between Benadryl and medications prescribed for high blood pressure. However, Benadryl can increase the side effects of metoprolol succinate (Toprol XL) and metoprolol tartrate (Lopressor), which can lead to low blood pressure, dizziness, and slow heart rate.

As mentioned above, Benadryl is an ingredient of many OTC cough and cold products. Benadryl doesn’t raise blood pressure by itself. These products contain decongestants such as pseudoephedrine that can increase blood pressure.

Other antihistamines

Taking Benadryl along with other antihistamines can increase the risk of side effects. This includes drugs like meclizine (Antivert), loratadine (Claritin), cetirizine (Zyrtec), hydroxyzine (Vistaril), and promethazine (Promethegan). Also, taking other diphenhydramine-containing products can lead to more severe side effects like dizziness, drowsiness, confusion, and inability to concentrate.

Antidepressants

Tricyclic antidepressants (TCAs), an older antidepressant class, and trazodone (Desyrel) have sedating effects.  Drug interactions between Benadryl and these specific antidepressants can increase the risk of side effects like drowsiness and reduced alertness. 

Sleeping medicines

Taking Benadryl with sedative-hypnotics (sleep aids) like eszopiclone (Lunesta), zolpidem (Ambien), or suvorexant (Belsomra) can increase the risk of side effects like extreme drowsiness, confusion, and difficulty concentrating. Prescription sleep medications and OTC sleep aids, such as melatonin and Unisom, should not be combined with Benadryl. An interesting fact to keep in mind is that, except for melatonin, the active ingredients in most OTC sleeping pills are antihistamines like Benadryl. 

Bowel disease medications

Certain medications used to treat bowel diseases, such as irritable bowel syndrome with diarrhea (IBS-D), can cause constipation as a side effect. In some rare cases, Benadryl can interact with these medications for IBS-D and worsen constipation. However, this is rare and only happens if you take high doses of Benadryl regularly over a long period.

Seizure medications

Certain medications used to treat seizures, such as zonisamide (Zonegran), can lead to increased body temperature and decreased sweating. Though not common, Benadryl interactions can worsen these side effects and may lead to heat stroke. Your healthcare professional will tell you to exercise caution, especially during vigorous exercise in warm weather, if you are on this combination of drugs.

Cannabis products

The use of cannabis and Benadryl together can lead to side effects like dizziness, drowsiness, confusion, and difficulty concentrating. These effects may be especially severe in elderly individuals who may also experience impaired judgment and coordination.

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What are Benadryl interactions?

Taking Benadryl with certain drugs can lead to possible interactions. If you have other medical conditions and are taking medications for them, or even if you only take OTC products like a multivitamin or supplements, you should ask your pharmacist or healthcare professional if Benadryl is right for you.

Keep in mind that different people may react differently to certain drugs, so promptly get medical care for severe side effects, such as an allergic reaction.

Tell your doctor or healthcare professional about all medications and health conditions, such as high blood pressure, before starting treatment. If there are known interactions between Benadryl and your other medications, a licensed healthcare professional can give you another treatment option for your medical conditions.

What is Benadryl?

Benadryl is a widely available over-the-counter antihistamine that contains the generic medication diphenhydramine. This medication dosage forms include:

• Diphenhydramine hydrochloride tablet

• Diphenhydramine hydrochloride capsule

• Diphenhydramine hydrochloride liquid-filled capsule

• Diphenhydramine hydrochloride solution

Generic diphenhydramine is available under brand names such as Benadryl, Children's Benadryl Allergy, Aler-Dryl, Diphenhist, Nytol, Pediacare Children’s Allergy, Benadryl Allergy Ultratab, Children's Benadryl Chewables tablets, and Siladryl. 

Diphenhydramine is also present in many combination medications such as Advil PM (ibuprofen / diphenhydramine), Aleve PM (naproxen / diphenhydramine), Motrin PM (ibuprofen / diphenhydramine), and others. Benadryl Itch Relief contains diphenhydramine in different dosage forms, such as zinc acetate solution, zinc acetate cream, or zinc acetate spray, to relieve skin symptoms related to allergic reactions.