Taking Benadryl With Clonazepam

Our pharmacist discusses what to be aware of when taking the combination of Benadryl (diphenhydramine) and clonazepam.

3 min read Updated Jun 2026 Read by 14,449 people
Taking Benadryl With Clonazepam
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Holly asked

I have severe anxiety and panic attacks. I have asked this question a hundred times to different doctors and pharmacists, but my anxiety won't let it rest. My question is about a drug interaction leading to death. I'm on Clonazepam.5mg which I took at 5 pm. Almost every night I take 1 Benadryl to help me sleep. It's 12:30 am now. Is it safe to take Benadryl now? I'm okay with drowsiness. I just don't want to over-sedate myself and stop breathing. I'm also on Prozac 20mg which I took today at 1 pm.

Sep 10, 2022
The quick answer
  • Both Benadryl and clonazepam depress the central nervous system and can cause additive effects like excess sedation and respiratory depression when taken together.
  • The risk of serious problems remains low in healthy individuals without sleep disorders taking usual doses, but the combination is generally not recommended.
  • Talk to your doctor about your specific situation since they know your full medical history and can determine if this combination is safe for you.
A quick summary of Dr. Brian Staiger, PharmD's full answer below, condensed by AI from that answer only (not from any outside source). The pharmacist's answer is the source of record.

Thanks so much for reaching out to us. I hope this answer helps to alleviate some of your fears.

Interaction Details

Both Benadryl (diphenhydramine) and clonazepam have CNS (central nervous system) depressant effects and are generally not recommended to be used together.

Taking both together can have additive effects which could lead to excess sedation and respiratory depression. The risk is greatly increased if you have a sleep-related breathing disorder such as sleep apnea or COPD. 

Having said that, the chance of fatal respiratory depression on the combination of Benadryl and clonazepam (at usual doses) is low in normal, healthy individuals. While the exact incidence of severe episodes of respiratory depression is unknown, the reported cases typically involved individuals who had underlying conditions, were on additional sedating medications, or were taking excessive doses.

In terms of the individual medications, collected data shows that benzodiazepines (such as clonazepam), as a class of medications, cause dose-dependent respiratory depression (i.e. high doses result in an increased risk). However, at usual, hypnotic doses, respiration is typically not affected in normal, healthy individuals.

Benadryl is not thought to cause respiratory depression in normal, healthy individuals with no conflicting factors. There does seem to be a small risk in individuals with sleep disorders and in those were take doses exceeding manufacturer recommendations. 

Taking Benadryl And Klonopin Together

It is extremely difficult to accurately anticipate how a certain combination of drugs will affect someone. What we know for sure is that there is an inherent, increased risk in combining multiple drugs that individually can cause respiratory depression. The most commonly reported interactions involve opioid (e.g. oxycodone) drugs but combining any drugs that cause CNS depression is a risk.

Overall, the combination of Benadryl and clonazepam heightens the risk of respiratory depression, but the risk remains small in healthy individuals with no underlying sleeping disorders. 

It puts health care providers in a difficult situation if you are looking for a definitive answer regarding whether or not you can take this combination of drugs together. There are many factors to consider and the exact risk is not known. Most will err on the side of caution and recommend against the combination unless you can be monitored to confirm that taking the drugs together will not significantly affect you.

Final Words

Lastly, Prozac (fluoxetine) is not typically associated with respiratory depression. 

If you are having trouble sleeping and or would like a recommendation for your specific situation, speak with your doctor. They have your full medical history and are in the best position to provide you with appropriate guidance. 

Thanks again for your question and feel free to reach back out anytime.

References & sources
  1. THE TOXIC EFFECTS OF ANTI-HISTAMINIC DRUGS — JAMA
  2. Respiratory depression in children receiving diazepam for acute seizures: a prospective study — PubMed
  3. Diphenhydramine Monograph — PubChem
Glossary — Terms in This Answer
CNS depressant
A medication that slows down brain and nervous system activity, reducing alertness and consciousness.
Additive effects
When two drugs combine to produce a stronger effect than either drug would cause alone.
Respiratory depression
A dangerous slowing or weakening of breathing that can reduce the amount of oxygen reaching the body.
Sleep apnea
A sleep disorder where a person temporarily stops breathing repeatedly during sleep.
COPD
A chronic lung disease that makes it difficult to breathe and includes conditions like emphysema and chronic bronchitis.
Benzodiazepines
A class of prescription medications that calm the nervous system and are commonly used to treat anxiety and sleep problems.
Dose-dependent
A characteristic where the strength of a drug's effect increases as the dose or amount taken gets larger.
Opioid
A class of powerful pain-relieving medications derived from or similar to opium that carry a high risk of respiratory depression.
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Dr. Brian Staiger, PharmD
About the pharmacist

Dr. Brian Staiger, PharmD

Clinical Pharmacy

Doctor of Pharmacy, board certified clinical pharmacist (BCPS), American Herbalist Guild, Medication Therapy Management certified

Brian Staiger, PharmD, BCPS, is a licensed pharmacist with more than 13 years of experience across retail pharmacy, clinical pharmacy, medication safety, pharmacy program development, and healthcare administration. He is the founder of HelloPharmacist.com, where he helps patients...

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