Important Benadryl (Diphenhydramine) Interactions to Know About

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Many people take allergy medicines without giving much thought to how they might mix with other prescriptions, supplements, or even alcohol. But with Benadryl, interactions can be surprisingly common, and sometimes serious. Understanding these risks can help you avoid unwanted side effects and use Benadryl more safely.

What Is Benadryl?

Benadryl is a widely available over-the-counter (OTC) antihistamine. It contains the generic medication diphenhydramine and is effective in relieving symptoms of allergies and allergic reactions. Diphenhydramine is available in various dosage forms, such as:

• Diphenhydramine hydrochloride tablet

• Diphenhydramine hydrochloride capsule

• Diphenhydramine hydrochloride liquid-filled capsule

• Diphenhydramine hydrochloride solution

Brand names of generic diphenhydramine include Benadryl, Children's Benadryl Allergy, Aler-Dryl, Diphenhist, Nytol, Pediacare Children’s Allergy, Benadryl Allergy Ultratab, Children's Benadryl Chewables tablets, and Siladryl. 

Notably, diphenhydramine is also present in various combination medications such as: 

• Advil PM (ibuprofen/diphenhydramine)

• Aleve PM (naproxen/diphenhydramine)

• Motrin PM (ibuprofen/diphenhydramine)

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.

What are Benadryl interactions?

Taking Benadryl with certain prescription drugs and over-the-counter products like multivitamins and supplements can lead to possible interactions. If you have other medical conditions and are on other medications, it’s crucial to consult your doctor or pharmacist before considering Benadryl treatment. 

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.

Which Medications Does Benadryl Interact With?

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. 

1. Alcohol 

Alcohol is a central nervous system (CNS) depressant, meaning it slows brain activity. If you drink alcohol while taking Benadryl, it can increase the sedating effect of Benadryl, leading to severe 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 and confusion, and a slowed breathing rate. These side effects can cause impaired alertness and focus, putting you at risk of injuries and accidents. 

2. 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), leading to low blood pressure, dizziness, and a slowed heart rate.

It’s also worth remembering that Benadryl is an ingredient in many OTC cough and cold products. While Benadryl itself doesn’t raise blood pressure, many of these products contain decongestants such as pseudoephedrine that can increase blood pressure.

3. Other Antihistamines

Taking Benadryl with other antihistamines can increase the risk of unwanted side effects and put you at risk of an antihistamine overdose. For example, drugs like: 

• Meclizine (Antivert)

• Loratadine (Claritin)

• Cetirizine (Zyrtec)

• Hydroxyzine (Vistaril)

• Promethazine (Promethegan)

Taking multiple diphenhydramine-containing products at the same time can cause severe side effects like dizziness, drowsiness, confusion, and inability to concentrate.

4. Sleep Aids

Taking Benadryl with sedative-hypnotics (sleep aids) can increase the risk of side effects like extreme drowsiness, confusion, and difficulty concentrating. Examples include prescription sleep medications such as eszopiclone (Lunesta), zolpidem (Ambien), or suvorexant (Belsomra), and OTC sleep aids such as melatonin and Unisom.

An interesting fact to keep in mind is that, except for melatonin, the active ingredients in most OTC sleeping pills are antihistamines like Benadryl. 

5. Anticholinergic Medications

Benadryl is an anticholinergic, meaning it can block certain nerve signals in the body. Taking it with other anticholinergic drugs can raise the risk of side effects like dry mouth, constipation, trouble urinating, blurred vision, and confusion.

Common examples of anticholinergic medications include:

• Certain antidepressants (amitriptyline, nortriptyline)

• Antipsychotics (quetiapine, olanzapine)

• Bladder medicines (oxybutynin, tolterodine)

• Parkinson’s drugs (benztropine, trihexyphenidyl)

Combining these medications can also increase the risk of falls and memory problems, especially in older adults. In most cases, it’s best to avoid combining Benadryl with other anticholinergic medicines.

6. Antidepressants

Certain antidepressants, such as tricyclic antidepressants (TCAs) (for example, amitriptyline), monoamine oxidase inhibitors (MAOIs), and trazodone (Desyrel) have sedating effects. Drug interactions between Benadryl and these antidepressants can increase the risk of side effects such as drowsiness and decreased alertness. Some of these drugs also have anticholinergic effects, which, as mentioned above, can add to Benadryl’s side effects.

7. Bowel Disease Medications

Certain medications used to treat bowel diseases like irritable bowel syndrome with diarrhea (IBS-D) can cause constipation as a side effect. In 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.

Benadryl (diphenhydramine) interacts with certain antipsychotic drugs, such as Seroquel (quetiapine), which can lead to new or worsening constipation and also more serious adverse events like a bowel blockage. 

As previously mentioned, many antipsychotics are also anticholinergic, and combining them with Benadryl may increase confusion, drowsiness, or memory problems.

8. Antiseizure Drugs

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

9. Cannabis Products

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

10. Opioids 

Both Benadryl and opioid pain medications have sedative effects. Taking them together can lead to extreme sleepiness. Examples of prescription opioid drugs include morphine, oxycodone, hydrocodone, and fentanyl.

Strategies to Prevent and Manage Diphenhydramine Interactions

Follow these tips to prevent adverse effects of Benadryl interactions:

• Tell your doctor or pharmacist about all the medications you’re on and if you have underlying health conditions, such as high blood pressure, lung conditions (asthma, emphysema, chronic bronchitis), glaucoma, or an enlarged prostate gland, before taking Benadryl.

• Make sure you read the label carefully. Products may have age-specific dosing instructions.

• Check the ingredients for those that are similar to diphenhydramine or that have known interactions, such as other antihistamines and sleep aids.

• Avoid alcohol while taking Benadryl. If you do plan to drink, talk to your healthcare provider for guidance. 

• Seek prompt medical care for any unusual or severe side effects that develop after you start treatment with Benadryl, such as an allergic reaction.

Frequently asked questions about Benadryl interactions

Can I Take Sudafed and Benadryl Together?

Yes, you can safely take Sudafed (pseudoephedrine) and Benadryl (diphenhydramine) together. Sudafed is a nasal decongestant that relieves symptoms like a stuffy nose and sinus congestion, while Benadryl is an antihistamine that relieves allergy symptoms such as sneezing, a runny nose, and itchy, watery eyes. 

These two medications work differently to relieve symptoms and are often combined in products to treat common colds and allergies.

Can You Take Benadryl With Nyquil?

Avoid taking Benadryl with Nyquil as both are antihistamines, and their combination can lead to unwanted side effects such as excessive drowsiness, dizziness, impaired coordination, and confusion. 

Some Nyquil products also contain diphenhydramine, the same active ingredient as Benadryl, which can lead to overdosing. 

Can You Take Benadryl With Prednisone?

Yes, in most cases, prednisone and Benadryl (diphenhydramine) are considered safe to take together, and are sometimes prescribed at the same time to manage severe allergic reactions. However, if you are prescribed prednisone for a chronic condition, check with your doctor before using Benadryl regularly, as frequent use may mask symptoms that need medical attention.

Does Benadryl Interact With Supplements?

Benadryl can interact with certain supplements, especially those that cause drowsiness or have sedative effects, such as valerian root, kava, melatonin, or ashwagandha. Always tell your doctor or pharmacist about any vitamins, herbs, or natural products you use so they can check for potential interactions.