What Antihistamines Are Most Similar To Benadryl?

In our latest question and answer, our pharmacist discusses what antihistamines are most like Benadryl.

Question

I am a senior citizen who took Benedryl OTC for allergies. It worked as no other OTC allergy med has since we were told to stop taking it. I would like to know what OTC allergy medicine would be comparable to Benadryl. I am 75 yrs old and have to take an allergy tablet every morning. I have taken cetirizine, loratadine, and cetirizine, none of which have even come close to working as well as Benadryl. Can you suggest an OTC that might come close to working as well as Benadryl? Thank you for your help.

Asked by Kathi On Jun 03, 2022

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Jun 04, 2022
Last updated Jun 04, 2022

Key points

  • Antihistamines are often grouped by 'generation' and 'chemical class'
  • Benadryl is a first-generation, ethanolamine class antihistamine
  • The most similar antihistamines to Benadryl include clemastine (Tavist), dimenhydrinate (Dramamine), diphenhydramine, doxylamine, brompheniramine, and chlorpheniramine

Hello and thanks for reaching out!

I'm more than happy to discuss this topic.

You're certainly not the first person to write to us looking for recommendations on antihistamines and it's not uncommon I hear about other antihistamines not working as well to treat allergy symptoms as Benadryl.

Even though Benadryl and the other drugs that come up often in this discussion (e.g. Claritin, Allegra, Xyzal, Zyrtec, etc...) are classified as 'antihistamines', there are several different classes of antihistamines, each with different properties, and thus, different effects.

Differentiating Antihistamines

There are several ways to group antihistamines. The two most common ways are by:

  • Generation
  • Chemical Class

Antihistamine Generation

In regard to generation, you may have heard the term 'first-generation' or 'second-generation' antihistamine.

'First-generation' antihistamines are older and have been on the market for a longer period of time than the 'second-generation' ones.

In general, first-generation antihistamines are shorter-acting (around 4-6 hours per dose) and more sedating. Second-generation ones are longer-acting and less sedating.

Most antihistamines when broken down into generations follow this pattern so, for example, Claritin (a second-generation antihistamine) is both longer-acting and far less sedating than Benadryl (a first-generation antihistamine).

Antihistamine Class

As mentioned, antihistamines can also be grouped by chemical class, and in many ways, the class an antihistamine is grouped in is more closely correlated to their overall effects. The following chemical classes are the most common:

  • Alkylamines
  • Piperazines
  • Piperidines
  • Ethanolamines

You stated in your question that you get the best effects from taking Benadryl, which is classified as an 'ethanolamine' antihistamine.

Ethanolamine antihistamines, in general, have much more pronounced 'anticholinergic' effects than other antihistamines, which include effects like sedation and 'drying'. This is why Benadryl is used often to help sleep and tends to be more effective at treating a runny nose and watery eyes.

These effects aren't always positive though.

Sedation isn't always an effect that is wanted, especially if you need to take something that works throughout the day for seasonal allergies. Drugs like Benadryl can also cause confusion and dry mouth, which can be both bothersome and dangerous.

Nevertheless, you asked about Benadryl and about how it works differently for you when compared to other antihistamines, and what I wrote above is why. You likely have symptoms that are simply better treated with the effects you get from Benadryl.

Antihistamine Breakdown

Below is a chart showing a breakdown of the most common antihistamines by generation and chemical class so you can compare them.

Chemical Class First-GenerationSecond-Generation
Alkylamines Brompheniramine, Chlorpheniramine Acrivastine
Piperazines Hydroxyzine, Meclizine Cetirizine (Zyrtec), Levocetirizine (Xyzal)
Piperidines Cyproheptadine, Ketotifen Desloratadine (Clarinex), Ebastine, Fexofenadine (Allegra), Loratadine (Claritin), Olopatadine
EthanolaminesClemastine, Dimenhydrinate, Diphenhydramine, Doxylamine --
EthylenediaminesAntazoline, Pyrilamine, Tripelennamine --
PhenothiazinesPromethazine-

What Is Most Like Benadryl?

Since you're specifically looking for an over-the-counter antihistamine option that is closest to the effects Bendaryl had for you, you should be looking for other first-generation antihistamines in the ethanolamine class or alkylamine class.

These drugs include:

  • Doxylamine
  • Clemastine
  • Brompheniramine
  • Chlorpheniramine

The closest to Benadryl structurally, and in terms of the overall effect, are doxylamine and clemastine.

Doxylamine is generally only marketed as a sleep aid (it is one of the active ingredients in NyQuil) but is an effective antihistamine nonetheless.

Clemastine is also available over the counter and is more often than doxylamine, actually marketed as an antihistamine. It is the active ingredient in the brand name product Tavist and DayHist.

If I had to pick one antihistamine, available over the counter, that is most similar to Benadryl in terms of effect, I would pick clemastine.

After doxylamine and clemastine, your next closest options are brompheniramine and chlorpheniramine.

These drugs have an advantage over Benadryl in that they last longer (8-12 hours versus 4-6). They are in a different chemical class, but, again, have similar overall effects.

Brompheniramine can be found in Dimetapp products while chlorpheniramine can be found in stand-alone products, like Chlor-Trimeton.

What About Other Options?

I won't spend too much time on second-generation antihistamines since you said they didn't work well for you.

I will say that most studies show that the second-generation antihistamines are just as effective as the first-generation ones and have the added benefit of having fewer side effects.

Nevertheless, there are certainly people who feel they get better allergy relief from first-generation ones than second-generation ones.

Aside from antihistamines, I would suggest you consider a steroid nasal spray for allergies as well, such as Flonase or Nasonex.

Nasal steroids have been shown to generally be more effective than oral antihistamines for seasonal allergy symptoms and are convenient in that they only need to be dosed once a day.

Final Words

I wanted to thank you again for your question!

Please feel free to write us again with any follow-up questions.

References

  • H1 Antihistamines: Current Status and Future Directions, PubMed
  • Intranasal corticosteroids compared with oral antihistamines in allergic rhinitis: A systematic review and meta-analysis, PubMed
  • Antihistamines and allergy, PubMed

About the Pharmacist

Dr. Brian Staiger, PharmD

Dr. Brian has been practicing pharmacy for over 13 years and has wide-ranging experiences in many different areas of the profession. From retail, clinical, program development, and administrative responsibilities, he's your knowledgeable and go-to source for all your pharmacy and medication-related questions! Dr. Brian Staiger also has herbalist training and educational certificates in the field of medical ethnobotany. Feel free to send him an email at Hello@HelloPharmacist.com! You can also connect with Dr. Brian Staiger on LinkedIn.

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