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When you experience symptoms of allergies, hay fever, or the common cold, all you want is a solution—fast. Benadryl quickly relieves symptoms of red, itchy, watery eyes, sneezing, runny nose, cough, and an itchy throat. For some people, it can help manage symptoms of insomnia, Parkinson’s disease, or motion sickness. But before seeking relief from Benadryl, you should know it does have certain drug interactions.
Benadryl is a valuable solution to many ailments, and it’s available by prescription and over-the-counter (OTC) as oral or chewable tablets, liquid gels, liquid medicine, and topical creams. To ensure you use it properly, learn how Benadryl interacts with medications and health conditions—and when you should stop using it.
How Benadryl works
Benadryl is a brand name for diphenhydramine, which belongs to the class of first-generation antihistamines. These drugs cross the blood-brain barrier to act in the central nervous system (CNS). Diphenhydramine can also be found in certain combination medications like Advil PM (ibuprofen/diphenhydramine) and Tylenol PM (acetaminophen/diphenhydramine).
When histamine binds to receptors, the process signals the reactions that cause allergy symptoms like itchy eyes or coughing. Benadryl’s main ingredient, diphenhydramine, blocks histamine receptors, thereby blocking the effects of histamines and reducing your allergy symptoms.
Because it crosses the blood-brain barrier, diphenhydramine also blocks some brain receptors, resulting in side effects such as drowsiness, dizziness, sleepiness, impaired coordination, and decreased activity in the part of your brain that controls coughing.
What not to take with Benadryl
To prevent drug interactions, tell your healthcare provider about any prescription drugs or OTC medications and vitamins or supplements you’re taking before taking Benadryl. Some drugs shouldn’t be taken together because of adverse drug interactions that can cause side effects or affect the efficacy of either drug.
If you take any of the following 8 drugs, you should talk with your healthcare provider before taking Benadryl.
1. Blood pressure medications
“Benadryl does not directly interact with blood pressure medications,” says William A. McCann, MD, the chief medical officer of Allergy Partners. “However, antihistamines such as Benadryl are often combined with decongestant medications such as pseudoephedrine, which can cause increased blood pressure.”
Benadryl may cause side effects with nebivolol—an FDA-approved medication for treating high blood pressure. “Nebivolol stays longer in the body because Benadryl slows the liver’s filtration,” says Benjamin Gibson, Pharm.D., an adjunct professor at the University of Texas at Austin. “This may cause lowering of blood pressure and side effects such as headache, dizziness, and changes in heart rate. Other blood pressure medications like lisinopril, losartan, verapamil, diltiazem, telmisartan, and candesartan do not have that interaction.”
According to the Centers for Disease Prevention and Control, 48% of Americans have high blood pressure. If you have high blood pressure, talk with your healthcare provider before taking Benadryl.
2. Anticholinergic drugs
“Acetylcholine is a chemical messenger that allows our nerve cells to communicate with one another and carry out essential functions within our bodies,” says Whitney Prude, Pharm.D., founder of Whole & Happy Living. “When acetylcholine is blocked, it interferes with signals in your body and results in common anticholinergic side effects like dry mouth, blurry vision, constipation, drowsiness, sedation, hallucinations, memory problems, and trouble urinating.”
Benadryl has some anticholinergic effects, and you will notice more side effects if you combine Benadryl and an anticholinergic such as atropine, benztropine, glycopyrrolate, or flavoxate, she says.
3. Benzodiazepines
Benzodiazepines—like diazepam, alprazolam, clonazepam, lorazepam, and oxazepam—are prescribed for insomnia, anxiety, muscle relaxation, or seizures.
Benadryl and benzodiazepines don’t interact directly with each other, but both can cause sedation in the CNS and combining the medications can amplify these effects, says Dr. Prude. “Benzodiazepines work by interacting with a receptor in the brain called the GABA type A receptor, which causes sedation—and, at higher doses, amnesia and unconsciousness,” she says. Benadryl causes sedation with its effect on the histamine receptor, she adds.
Benzodiazepines and Benadryl should not be taken together, says Dr. Prude. She recommends second-generation antihistamines to treat allergies while taking a benzodiazepine. Claritin (loratadine), Zyrtec (cetirizine), and Xyzal (levocetirizine dihydrochloride) are second-generation antihistamines that cross the blood-brain barrier to a much lesser extent and have significantly fewer side effects like drowsiness and impairment.
4. Antidepressants
Antidepressants treat clinical depression, anxiety, chronic pain, and addictions. “Certain antidepressants can interact with diphenhydramine,” Dr. McCann says. “These include tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and monoamine oxidase inhibitors (MAOIs).”
Dr. McCann lays out how each of these classes of antidepressants interacts with Benadryl:
- TCAs are closely related to antihistamines, and they cause sedation by blocking histamine, just like diphenhydramine. When taken together, you could become too sedated with symptoms such as dizziness, blurred vision, and dry mouth.
- SSRIs and SNRIs can make some people drowsy, especially when you first take them. Drowsiness increases when combined with diphenhydramine.
- Similar to diphenhydramine, MAOIs can cause side effects like dry mouth, drowsiness, and dizziness. Taking Benadryl with MAOIs can exacerbate them.
5. Sleeping aids
Current statistics suggest that 50 to 70 million people in the U.S. have a sleep disorder. People often use sleeping aids like melatonin or doxepin to induce sleep or manage insomnia.
“Diphenhydramine can make people feel drowsy, and combining it with other sleep medications can worsen this effect,” says Dr. McCann. Diphenhydramine, the active ingredient in Benadryl Allergy, is commonly found in nonprescription sleep aids, he says. Be cautious not to consume too much when treating allergies and insomnia. Double check labels, or better yet, ask your pharmacist to make sure you aren’t doubling up on diphenhydramine.
6. Alcohol
Alcohol and Benadryl have sedative functions, so you can experience adverse effects when taken together or within the same time frame. Combining alcohol and Benadryl can lead to drowsiness, dizziness, difficulty concentrating, poor motor skills, and an increased risk of drug overdose. You shouldn’t mix the two, especially in older adults who metabolize alcohol more slowly.
7. Other antihistamines
Dr. Prude says Benadryl (diphenhydramine) and other first and second-generation antihistamines relieve allergy symptoms by blocking histamine receptors.
“Because these medications all work by the same mechanism, there is very little to no benefit to taking more than one,” she says. “It only results in an increased risk of sedation, impaired mental state, and psychomotor performance, to name a few.”
However, there are exceptions for people who have severe allergies and are prescribed high doses of antihistamine under doctor supervision.
8. Opioids
Healthcare providers commonly prescribe opioids containing ingredients like tramadol, methadone, oxycodone, fentanyl, or hydrocodone to treat moderate or severe pain. Experts suggest that using the medications together can cause adverse reactions due to synergistic activity—Benadryl and an opioid combine to produce more potent sedative effects than if taken alone.
About 4% of drug overdose deaths between 2019 and 2020 involved diphenhydramine and opioids like fentanyl, according to the CDC’s weekly morbidity and mortality report of October 2022. The combination of drugs caused stronger sedation in those who took them. The CDC urges patients to use only verifiable pharmacies to avoid illegally manufactured opioids containing diphenhydramine (some manufacturers add it to prevent side effects like itching). People who unknowingly consume these medicines are more susceptible to drug overdose.
Who should not take Benadryl?
People with a history of allergic reactions to Benadryl should never take it. Beyond that, Dr. McCann says children should avoid it unless directed by a physician.
Additionally, if you have the following conditions, you should not take Benadryl:
- Narrow-angle glaucoma: This occurs when fluid cannot be drained from the eye because of the narrowing of the iris and cornea. Benadryl worsens the condition and increases the risk of angle closure glaucoma—a medical condition associated with sudden extreme pressure in the eyes. Its symptoms include headaches, blurred vision, eye pain, nausea, and vomiting.
- Pregnancy: Occasionally, taking the proper dose of Benadryl may be safe during pregnancy. However, it’s best to talk with your OB-GYN before doing so. Some studies have reported adverse effects of diphenhydramine during pregnancy.
- Breastfeeding: The American Academy of Family Physicians recommends waiting to take Benadryl until immediately after breastfeeding since it’s secreted in breast milk and can cause drowsiness and fussiness in babies. Ask your healthcare provider before taking Benadryl while nursing.
- Epilepsy: Diphenhydramine can trigger seizures in people with a history of epilepsy; it’s best to avoid it.
- Prostate problems: Benign prostate hyperplasia (BPH) mostly affects older men. The prostate grows, leading to problems such as frequent urination, a weak stream of urine, and dripping urine. Benadryl worsens these symptoms of BPH and can cause urinary retention.
- Dementia: Acetylcholine is an important brain chemical for memory and learning; you produce less as you age. Benadryl blocks acetylcholine, and in the long-term, it can lead to progressive memory impairment and might worsen dementia. Long-term use of Benadryl has been associated with dementia.
- Heart disease: First-generation antihistamines are known to increase heart rate in some people. Consult your healthcare provider before using Benadryl if you have any heart condition.
- Age: Benadryl is not recommended for older adults. “The risk of serious side effects of Benadryl—including confusion, dizziness, urinary retention, and liver or kidney issues—is increased in people 65 and older,” says Dr. McCann. He adds there’s an increased risk of drug interactions.
- Breathing problems: If you have asthma, emphysema, chronic bronchitis, or other breathing problems, don’t use Benadryl. It can dry up the mucus produced in the lungs, making coughing it up more difficult.
How to prevent Benadryl interactions
The best thing to do to prevent a Benadryl interaction is to not take it if you are taking any of the medications or have any of the conditions discussed above. Before taking Benadryl, tell your healthcare provider about every medication you currently take and your health conditions, so they can advise you on the best ways to avoid drug interactions. Because there are many options for allergy treatments, your healthcare provider or pharmacist can help you select an appropriate product.
You should take Benadryl only as directed by your healthcare provider or as recommended on the drug label. The usual dose for adults and children over 12 years is one or two 25 mg tablet(s)—and one 25 mg tablet for children between 6 and 12 years. It’s not recommended for children younger than 6. The medication should be taken no more than every four to six hours, or at most six times a day.
Additionally, you should not use Benadryl in the following instances:
- To induce sleep in children
- If driving, because diphenhydramine causes drowsiness
- With sedating medicine, as it may increase drowsiness
When to see a doctor for a diphenhydramine interaction
It’s normal for Benadryl to cause drowsiness and mind fog and to affect some of your movements. However, Dr. Prude warns that if you experience any of the following side effects, you should stop taking the medication immediately and see your healthcare provider:
- Clumsiness or unsteadiness
- Convulsions (seizures)
- Severe drowsiness
- Severe dryness of mouth, nose, or throat
- Feeling faint
- Flushing or redness of the face
- Hallucinations (seeing, hearing, or feeling things that are not there)
- Shortness of breath or troubled breathing
- Trouble sleeping
When in doubt, discuss Benadryl use and drug information with a healthcare professional or pharmacist. They can provide medical advice and alternate, safer options if needed.
