Key takeaways:
Diphenhydramine (Benadryl) is an over-the-counter antihistamine commonly used to treat allergy symptoms. It’s also used as a sleep aid and found in many cough and cold products.
Many medications can interact with diphenhydramine. Most commonly, these include medications that make you feel drowsy. Sometimes this can result in severe drowsiness and slowed breathing.
Review your medications and supplements with your healthcare team, especially your prescriber and pharmacist. They can help you avoid or manage potential interactions.
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If you’ve ever had allergy symptoms, you’re probably familiar with diphenhydramine (Benadryl). You may have even used this medication to help you sleep, or for a cough or cold. Diphenhydramine is available over the counter (OTC) as tablets, capsules, and liquids. It’s also available as a topical cream for itchy skin.
Diphenhydramine is an older, first-generation antihistamine. The oral forms are known to cause more drowsiness compared to newer antihistamines. This side effect can intensify if you take it with other sedating medications (or alcohol). But these interactions may not be obvious or easy to navigate. That’s because diphenhydramine is included in many combination OTC products.
Some diphenhydramine interactions may be mild, while others may be more serious. So, it’s important to know what to look for before you start taking it.
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Diphenhydramine (Benadryl) interactions at a glance
Diphenhydramine interacts with a number of medications and substances. Understanding these interactions can help you avoid unwanted side effects.
Keep an eye out interactions like these:
Sedating medications, such as benzodiazepines, sleeping pills, and muscle relaxers
Opioid pain medications
Several antidepressants and antipsychotics
Medications that affect your heartbeat
Certain blood pressure medications
Other anticholinergic medications, such as those used to treat Parkinson’s disease or bladder conditions
Other antihistamines
Alcohol
Certain supplements, such as valerian or kava
Here, we’ll discuss how to manage seven notable diphenhydramine interactions. Keep in mind that this isn’t a complete list.
1. Sleeping medications
It’s estimated that 50 to 70 million people in the U.S. experience sleep problems. If this sounds like you, chances are you’ve given OTC sleep aids a try. Prescription sleeping medications, such as zolpidem (Ambien) and eszopiclone (Lunesta), are also frequently used.
Diphenhydramine can make people feel drowsy. And combining it with other sleep medications can worsen this effect. What’s more, diphenhydramine is commonly found in OTC sleep aids. So, you may be taking too much diphenhydramine if you’re taking it for allergies and for sleep.
It’s best to avoid diphenhydramine while you’re taking sleep medications. Your prescriber or pharmacist can recommend a safer combination.
2. Opioids
Opioids are a medication class used to treat pain. Examples include oxycodone (OxyContin), morphine, and tramadol (ConZip). They work by blocking pain signals in the brain and spinal cord. Like with diphenhydramine, sedation (feeling tired or sleepy) is a common side effect.
Diphenhydramine can worsen sedation already caused by an opioid. This can raise the risk of falls and other injuries. And too much sedation may cause slowed breathing that can be life-threatening.
Benadryl side effects: Learn about common Benadryl side effects, plus tips on how to manage them.
Countdown to symptom relief: How long does it take Benadryl to work? See how pharmacists answer this and other frequently asked questions about Benadryl.
Considering Benadryl as a sleep aid? Benadryl is known for causing drowsiness, but is it OK to take it to help you sleep?
If you’re taking an opioid medication, ask a healthcare professional about safer allergy, sleep, or cold medications you can take.
3. Benzodiazepines
Benzodiazepines are medications that work by slowing down activity in your brain. They’re used for many different conditions, including anxiety and seizures. Some are also used for sleep problems. Examples of benzodiazepines include alprazolam (Xanax), lorazepam (Ativan), and temazepam (Restoril).
Diphenhydramine shares many of the same side effects as benzodiazepines. These include drowsiness, confusion, and dizziness. When taken together, these side effects can become more intense and potentially dangerous.
Some people take benzodiazepines as needed, while others take them every day. Talk to a healthcare professional about how best to handle this interaction with your current regimen.
4. Anticholinergic medications
Anticholinergics are medications that block a chemical called acetylcholine in the nervous system. Acetylcholine is important for the functioning of your bladder, eyes, gut, and other organs. Common anticholinergic side effects include constipation, blurry vision, and confusion.
Oxybutynin (Ditropan) and scopolamine (Transderm Scop) are two popular examples of anticholinergic medications. And diphenhydramine is considered an anticholinergic, too.
If you take diphenhydramine with another anticholinergic, these side effects and others could worsen. Older adults and people with dementia are even more sensitive to these effects. So, it’s important to speak to a healthcare professional about safer alternatives.
5. Antidepressants
Certain antidepressants can interact with diphenhydramine. These include:
Tricyclic antidepressants (TCAs), such as amitriptyline and doxepin (Silenor, Zonalon, Prudoxin)
Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac) and paroxetine (Paxil)
Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine (Effexor XR) and duloxetine (Cymbalta)
Monoamine oxidase inhibitors (MAOIs), such as selegiline (Emsam, Zelapar) and tranylcypromine (Parnate)
TCAs are closely related to antihistamines. In fact, they were developed from them in the 1950s. They cause sedation by blocking histamine, just like diphenhydramine. When taken together, you could become too sedated. Dizziness, blurred vision, and dry mouth may also become worse.
SSRIs and SNRIs can also make some people feel drowsy, especially when you first start taking them. Drowsiness may be worse when they’re combined with diphenhydramine.
Similar to diphenhydramine, MAOIs can cause side effects like dry mouth, drowsiness, and dizziness. Taking them together can worsen these side effects.
Check with your prescriber or pharmacist before combining an antidepressant with diphenhydramine.
6. Muscle relaxants
Muscle relaxants are used to treat muscle pain, spasms, and stiffness. Examples include cyclobenzaprine (Amrix) and carisoprodol (Soma). These medications work in the brain and nervous system to help relieve muscle spasms. And a common side effect is sedation.
Cyclobenzaprine’s chemical structure looks similar to diphenhydramine. Researchers think this plays a role in its sedating effect. Other muscle relaxants, like carisoprodol, work similarly to benzodiazepines in the brain. This is thought to cause sedation as a side effect.
Taking a muscle relaxant together with diphenhydramine can cause serious sedation. For your safety, it’s best to avoid this combination.
7. Alcohol
You might have seen the warning on your diphenhydramine bottle to avoid alcoholic drinks. It has this warning because alcohol can enhance the sedating effects of diphenhydramine.
This combination can make you feel dizzy and confused. And it can also affect your alertness and ability to drive or perform other tasks safely. So, it’s best to avoid drinking alcohol while taking diphenhydramine.
How can you avoid or manage potential interactions with diphenhydramine?
There are a few things you can do to prevent or manage interactions with diphenhydramine.
Keep an up-to-date medication list. Make sure to include prescription and OTC products on the list. Your pharmacist or prescriber can check for any potential interactions.
Read labels. Diphenhydramine is found in many OTC products. Before taking a new medication, read the label. Make sure you understand the ingredients and side effects. This can help you avoid diphenhydramine, if necessary. You’ll also be able to avoid taking multiple products that contain diphenhydramine at the same time.
Avoid similar ingredients. Avoid taking medications with similar ingredients to diphenhydramine, like other antihistamines. Examples include doxylamine (Unisom) and hydroxyzine (Vistaril). Doing so could cause more side effects.
Follow instructions. In some cases, a healthcare professional might say it’s OK to combine medications. It’s important to follow their instructions for when and how to take your medications to minimize side effects.
Avoid alcohol. It’s best to avoid alcohol altogether while taking diphenhydramine. But if you’re planning on having a drink, check with a healthcare professional. They can give you guidance on what may be a safe amount to drink with your medications.
Frequently asked questions
You can take melatonin and Benadryl together, but it’s usually not recommended. Both can make you feel drowsy, dizzy, or groggy — especially the next day. Taking them at the same time may also make it harder to think clearly or stay alert. To avoid unwanted side effects, many healthcare professionals suggest sticking with just one or the other. If you’re thinking about taking both, check with your healthcare team first.
Yes, it’s generally safe to take Benadryl and Tylenol (acetaminophen) together. There’s no known interaction between them, and several over-the-counter products actually combine both ingredients into one pill. Tylenol PM (acetaminophen / diphenhydramine) is one example of many. Just be sure to follow the dosage instructions for each medication and avoid taking more than recommended.
Yes, Benadryl and Advil (ibuprofen) can usually be taken together. You’ll even find them combined in products such as Advil PM (ibuprofen / diphenhydramine). These medications work in different ways and don’t have any known interactions. Just be sure to use them as directed and not for longer than needed. They each have possible long-term side effects.
You can take melatonin and Benadryl together, but it’s usually not recommended. Both can make you feel drowsy, dizzy, or groggy — especially the next day. Taking them at the same time may also make it harder to think clearly or stay alert. To avoid unwanted side effects, many healthcare professionals suggest sticking with just one or the other. If you’re thinking about taking both, check with your healthcare team first.
Yes, it’s generally safe to take Benadryl and Tylenol (acetaminophen) together. There’s no known interaction between them, and several over-the-counter products actually combine both ingredients into one pill. Tylenol PM (acetaminophen / diphenhydramine) is one example of many. Just be sure to follow the dosage instructions for each medication and avoid taking more than recommended.
Yes, Benadryl and Advil (ibuprofen) can usually be taken together. You’ll even find them combined in products such as Advil PM (ibuprofen / diphenhydramine). These medications work in different ways and don’t have any known interactions. Just be sure to use them as directed and not for longer than needed. They each have possible long-term side effects.
The bottom line
Diphenhydramine (Benadryl) is a common over-the-counter (OTC) medication used for allergies, sleep, and cold symptoms. But it has several important interactions to know about. Most commonly, these include alcohol and other medications that can make you drowsy. In some cases, these diphenhydramine interactions can lead to dangerous levels of sedation, dizziness, and breathing problems.
Talk with your healthcare team before starting any new medications or supplements. They can check for any interactions with your current medications. Some interactions may be manageable, while others should be avoided entirely.
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References
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