This article describes possible interactions with diphenhydramine oral solution that’s available by prescription. Interactions can cause a drug to have a different effect on the body than expected. Interactions can occur due to medications, alcohol, or certain health conditions.
Diphenhydramine comes as a prescription oral solution that you swallow. It’s also available as a solution that’s injected into your muscle or vein.
Over-the-counter (OTC) forms of diphenhydramine also are available. See the “Questions about diphenhydramine and interactions” section to learn more.
Other drugs and diphenhydramine
The drugs in the list below may interact with diphenhydramine oral solution. This article doesn’t include all drugs that may interact with diphenhydramine.
Drug classes or drugs that may interact with diphenhydramine oral solution include:
- monoamine oxidase inhibitors (MAOIs):
- drug examples: phenelzine (Nardil), isocarboxazid (Marplan)
- what might happen: can increase the effect of and risk of side effects of diphenhydramine
- opioids:
- sedatives:
- drug examples: eszopiclone (Lunesta), zolpidem (Ambien)
- what might happen: can increase the risk of side effects of diphenhydramine and the sedative drug
- lofexidine (Lucemyra):
- what might happen: can increase the risk of side effects of diphenhydramine and lofexidine
- meclizine (Antivert):
- what might happen: can increase the risk of side effects of diphenhydramine and meclizine
- pitolisant (Wakix):
- what might happen: can make pitolisant less effective
- primidone (Mysoline):
- what might happen: can increase the risk of side effects of diphenhydramine and primidone
- rolapitant (Varubi):
- what might happen: can increase the risk of side effects of diphenhydramine
- thioridazine:
- what might happen: can increase the risk of side effects of diphenhydramine and thioridazine
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Certain health conditions or other factors could increase some risks with diphenhydramine oral solution. Because of this, doctors may not prescribe diphenhydramine in these cases. These health conditions or other factors are called contraindications.
Here’s a list of contraindications for diphenhydramine oral solution:
- Newborns or premature infants. Doctors will not prescribe diphenhydramine for newborns or premature infants. This is due to the risk of serious side effects.
- Breastfeeding. If you breastfeed, taking diphenhydramine oral solution may cause side effects in your child.
- Past allergic reaction to diphenhydramine. If you’ve ever had an allergic reaction to diphenhydramine oral solution, taking it again may cause another allergic reaction.
Before starting treatment with diphenhydramine, tell your or your child’s doctor if anything listed above relates to you or your child. They can recommend whether you or your child should take diphenhydramine.
Questions about diphenhydramine and interactions
Here you’ll find answers to some common questions about diphenhydramine and possible interactions.
Does diphenhydramine interact with blood pressure medications?
Most blood pressure medications aren’t expected to interact with diphenhydramine. But some medications that treat high blood pressure and certain other heart conditions may interact with it. These medications include nebivolol (Bystolic) and metoprolol (Lopressor, Toprol XL).
A specific enzyme (special type of protein) in the body helps break down nebivolol or metoprolol after you take a dose. But diphenhydramine can block the action of this enzyme. This can cause the amount of nebivolol or metoprolol to increase in your body. In turn, this can increase the effect of nebivolol or metoprolol and lead to side effects.
It’s typically safe to take either nebivolol or metoprolol and diphenhydramine together. But if you do, your doctor may want to monitor you more closely for side effects.
Tell your doctor or pharmacist if you take blood pressure medication. They can check whether it might interact with diphenhydramine.
Does diphenhydramine interact with acetaminophen?
No, diphenhydramine and acetaminophen t. Studies don’t show interactions between these two drugs.
Diphenhydramine interacts with opioids, such as hydrocodone and oxycodone. Diphenhydramine also interacts with opioids that contain acetaminophen. Some examples are hydrocodone/acetaminophen (Anexsia) and oxycodone/acetaminophen (Oxycet). But the interaction in these opioid combination drugs is due to the opioid, not acetaminophen.
To learn more about interactions with diphenhydramine and pain relievers, talk with your doctor or pharmacist.
Does diphenhydramine interact with dextromethorphan?
It depends. When taking them at approved or recommended doses, diphenhydramine and dextromethorphan usually don’t interact.
But both diphenhydramine and dextromethorphan can cause central nervous system (CNS) depression. With CNS depression, functions of the CNS (which consists of your brain and spinal cord) slow down. This can lead to symptoms such as drowsiness, slurred speech, and problems with coordination. Severe cases can result in slowed breathing and coma, but this is rare.
When taking it at recommended doses, dextromethorphan doesn’t usually cause CNS depression. But if you misuse the drug, it can. (With misuse, a drug is taken in a way other than how it’s prescribed or recommended.) This might occur by taking a dose higher than the drugmaker or your doctor recommends. This risk increases further by taking diphenhydramine after misusing dextromethorphan.
Older adults (age 65 years and above) may experience symptoms of an interaction if they take diphenhydramine along with dextromethorphan. In general, older adults are at higher risk of CNS depression.
Before taking diphenhydramine along with dextromethorphan, talk with your pharmacist or doctor. They can discuss safe dosages of dextromethorphan with you. They can also discuss whether it’s safe for you to take these drugs together.
Does diphenhydramine oral solution have interactions that differ from the over-the-counter (OTC) forms of diphenhydramine?
No, it doesn’t. Interactions of diphenhydramine don’t differ based on the form, including prescription and OTC forms. This article discusses interactions of the prescription oral solution. But these interactions also apply to OTC forms of diphenhydramine, such as oral tablets, capsules, and liquid.
Talk with your doctor or pharmacist to learn more about how prescription and OTC forms of diphenhydramine compare.
Alcohol and diphenhydramine
Diphenhydramine oral solution is known to interact with alcohol.
Taking diphenhydramine oral solution and drinking alcohol may cause central nervous system (CNS) depression. (The CNS is your brain and spinal cord.) Symptoms can include:
- problems with coordination and balance
- drowsiness
- slurred speech
- slowed breathing, in extreme cases
- coma, in extreme cases or if untreated
Due to this risk, your doctor likely will suggest avoiding alcohol while you’re taking diphenhydramine. If you drink alcohol and have concerns about avoiding it while taking diphenhydramine oral solution, talk with your doctor.
Other interactions and diphenhydramine
Interactions can occur with supplements, foods, vaccines, and some lab tests. Below you can learn whether diphenhydramine oral solution has these interactions.
The information below doesn’t include all other interactions possible with diphenhydramine.
Diphenhydramine and supplements
Before taking diphenhydramine oral solution, tell your doctor and pharmacist about any herbs you take, as well as vitamins and supplements. Doing so may help you avoid interactions.
Diphenhydramine can interact with melatonin supplements. Taking diphenhydramine along with melatonin can increase the risk of central nervous system (CNS) depression as a side effect. (The CNS is your brain and spinal cord.) This especially includes drowsiness and sleepiness. Talk with your doctor or pharmacist before taking melatonin supplements with diphenhydramine.
If you have questions about interactions that may affect you, talk with your doctor or pharmacist.
Diphenhydramine interactions with herbs
Diphenhydramine oral solution may interact with valerian (also called valerian root) and kava root. These herbs are often used to aid sleep.
Taking diphenhydramine along with valerian or kava root may lead to excessive drowsiness. It also causes slowed breathing in extreme cases.
Because of this, ask your doctor or pharmacist before taking any of these products while taking diphenhydramine oral solution.
Diphenhydramine interactions with vitamins
Diphenhydramine oral solution isn’t known to interact with any vitamins. But this doesn’t mean interactions with vitamins can’t happen or won’t be identified later.
Because of this, ask your doctor or pharmacist before taking any of these products while taking diphenhydramine oral solution.
Diphenhydramine and food
Diphenhydramine oral solution can interact with drinks, such as teas, that are made with valerian or kava root. This interaction can cause central nervous system (CNS) depression. (The CNS is your brain and spinal cord.) The condition leads to symptoms like coordination and balance problems, difficulty thinking clearly, and drowsiness.
Because of this, talk with your doctor or pharmacist about what foods you should avoid while taking diphenhydramine oral solution.
Diphenhydramine and vaccines
Diphenhydramine oral solution isn’t known to interact with any vaccines. But this doesn’t mean interactions with vaccines can’t happen or won’t be identified later.
Because of this, talk with your doctor or pharmacist before receiving any vaccines while taking diphenhydramine oral solution.
Diphenhydramine and lab tests
Diphenhydramine oral solution isn’t known to interact with lab tests. But this doesn’t mean interactions with lab tests can’t happen or won’t be identified later.
Because of this, talk with your doctor or pharmacist before having any tests while taking diphenhydramine oral solution.
Diphenhydramine and cannabis or CBD
Reports have shown that cannabis (commonly called marijuana) and cannabis products may interact with diphenhydramine. Cannabidiol (CBD) is an example of a cannabis product.
Taking diphenhydramine and using cannabis can increase the risk of side effects from diphenhydramine and cannabis. In particular, these include drowsiness and problems with balance and coordination.
Before you take diphenhydramine, tell your doctor and pharmacist if you use cannabis. Doing so may help prevent possible interactions.
Note: Cannabis is illegal at a federal level but is legal in many states to varying degrees.
Health factors and diphenhydramine
Certain medical conditions or other health factors may increase the risk of interactions with diphenhydramine oral solution. Keep in mind that interactions could lead to side effects or affect how well the drug works. Before taking diphenhydramine, tell your doctor about your health history. They’ll determine whether diphenhydramine is right for you.
These health conditions or other factors might interact with diphenhydramine oral solution:
- asthma
- bladder neck obstruction
- enlarged prostate
- glaucoma, especially narrow-angle glaucoma
- heart disease
- high blood pressure
- hyperthyroidism
- obstruction in your stomach or duodenum
- peptic ulcer
- pregnancy or breastfeeding
- past allergic reaction to diphenhydramine
Preventing diphenhydramine interactions
You may be able to help avoid certain interactions with diphenhydramine oral solution. Before taking this drug, you may want to discuss possible interactions with your doctor and pharmacist.
Things to consider include:
- Whether you drink alcohol or use cannabis.
- Other medications and herbs you take, as well as vitamins and supplements. Your doctor or pharmacist can help you fill out a medication list.
- What to do if you’re prescribed a new drug while taking diphenhydramine oral solution.
Taking diphenhydramine exactly as prescribed can also help prevent interactions.
What to ask your doctor
If you have questions about diphenhydramine and possible interactions, talk with your doctor.
Questions you may want to ask your doctor include:
- Does the dose of diphenhydramine oral solution affect my risk of interactions?
- If diphenhydramine oral solution interacts with a health condition I have, can I still take it?
- Should I let you know if I make lifestyle changes, such as to my diet or exercise routine?
Disclaimer: Optum Perks has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.