What are the alternatives to Diphenhydramine (Benadryl) creams?

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Last updated: May 5, 2025View editorial policy

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From the Guidelines

Topical doxepin is a recommended alternative to Benadryl creams for treating skin itching and allergic reactions, but its use should be limited to 8 days and 10% of body surface area due to concerns about allergic contact dermatitis and toxicity 1. When considering alternatives to Benadryl creams, it's essential to prioritize options that are effective and safe.

  • Hydrocortisone creams (0.5-1%) are widely available over-the-counter and can reduce inflammation and itching, making them a viable alternative to Benadryl creams.
  • Topical capsaicin has been promoted as an antipruritic agent, but its use is not recommended except in uraemic pruritus, and its efficacy in other contexts is limited 1.
  • Calamine lotion is not recommended due to a lack of evidence supporting its use in treating pruritus 1.
  • Other options like menthol, crotamiton 10% lotion, and topical anaesthetic spray ethyl chloride may have some benefits, but their effectiveness is not well-established 1. It's crucial to note that Benadryl cream can cause skin sensitization with repeated use, and many people prefer options without diphenhydramine's potential for drowsiness when absorbed through the skin.
  • Non-drowsy oral antihistamines like cetirizine (Zyrtec), loratadine (Claritin), or fexofenadine (Allegra) can also help manage skin allergies without the sedating effects of Benadryl. For persistent or severe skin conditions, it's essential to consult a healthcare provider as prescription-strength options may be necessary.
  • Recent studies have not provided significant evidence to support the use of other compounds, making topical doxepin a preferred alternative to Benadryl creams 1.

From the Research

Alternatives to Benadryl Creams

There are several alternatives to Benadryl creams for treating skin conditions such as eczema and atopic dermatitis. Some of these alternatives include:

  • Topical corticosteroids, which are classified by strength and can be used to treat inflammatory skin conditions 2
  • Pimecrolimus, a topical cream that has been shown to be effective in treating eczema and atopic dermatitis, although it may be less effective than topical corticosteroids 3, 4
  • Tacrolimus, a topical cream that has been shown to be effective in treating eczema and atopic dermatitis, and may be more effective than pimecrolimus in some cases 3, 4
  • Topical antibiotics, although these may be less effective than other treatments and may have uncertain harm 4
  • Crisaborole and difamilast, which may be intermediately effective but have uncertain harm 4
  • Delgocitinib and ruxolitinib, which may be effective in treating eczema and atopic dermatitis, although more research is needed to confirm their efficacy 4

Considerations for Use

When considering alternatives to Benadryl creams, it's essential to take into account the potential risks and benefits of each treatment. For example:

  • Topical corticosteroids can have adverse effects such as atrophy, striae, and rosacea, especially with prolonged use or high potency 2
  • Pimecrolimus and tacrolimus may be associated with skin burning and other adverse effects, although these are generally considered to be safe and effective treatments 3, 4
  • Topical antibiotics may be less effective than other treatments and may have uncertain harm, although they may still be useful in certain cases 4

Evidence for Efficacy

The evidence for the efficacy of these alternatives to Benadryl creams is based on a range of studies, including:

  • A systematic review and network meta-analysis of randomized trials, which found that pimecrolimus, tacrolimus, and moderate-potency topical corticosteroids were among the most effective treatments for eczema and atopic dermatitis 4
  • A Cochrane review, which found that pimecrolimus was less effective than topical corticosteroids but still a useful treatment option for eczema and atopic dermatitis 3
  • A literature review, which found that newer antihistamines such as loratadine and desloratadine may be safer and more effective than diphenhydramine (Benadryl) for treating acute allergic reactions 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Topical Corticosteroids: Choice and Application.

American family physician, 2021

Research

Topical pimecrolimus for eczema.

The Cochrane database of systematic reviews, 2007

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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