What are the comparisons and differences between Chlorpheniramine (Chlorpheniramine) and Diphenhydramine (Diphenhydramine)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: May 17, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Chlorpheniramine is generally preferred over diphenhydramine for treating allergic rhinitis due to its lower sedative effects and potential for less performance impairment, as supported by the most recent guidelines 1. When comparing chlorpheniramine and diphenhydramine, several key differences emerge:

  • Sedation: Chlorpheniramine is less sedating than diphenhydramine, making it more suitable for daytime use 1.
  • Dosing: Chlorpheniramine is typically taken at 4 mg every 4-6 hours, while diphenhydramine is usually dosed at 25-50 mg every 4-6 hours.
  • Anticholinergic effects: Diphenhydramine has stronger anticholinergic effects, potentially causing more dry mouth, urinary retention, and blurred vision.
  • Half-life: Chlorpheniramine has a longer half-life (20-24 hours) compared to diphenhydramine (2-8 hours), allowing for less frequent dosing. Both medications work by blocking H1 histamine receptors, preventing histamine from triggering allergy symptoms. However, due to the potential for significant sedation, performance impairment, and anticholinergic effects, diphenhydramine should be used with caution, especially in older adults and those with certain medical conditions like glaucoma, prostatic hypertrophy, or asthma 1. In terms of specific patient populations, older adults are more sensitive to the psychomotor impairment promoted by first-generation antihistamines like diphenhydramine, and their use should be approached with caution in this population 1. Overall, the choice between chlorpheniramine and diphenhydramine should be based on individual patient needs and medical history, with a preference for chlorpheniramine due to its lower sedative effects and potential for less performance impairment 1.

From the Research

Comparison of Chlorpheneramine and Diphenhydramine

  • Chlorpheneramine and diphenhydramine are both first-generation antihistamines, which can have adverse effects on the central nervous system, such as sedation 2.
  • Diphenhydramine has been shown to impair psychomotor performance and cognitive function 3.
  • Chlorpheneramine, on the other hand, has been reported to cause anaphylaxis in some cases, with 17 out of 54 patients experiencing anaphylaxis due to chlorpheniramine-induced adverse drug reactions 4.
  • Both chlorpheneramine and diphenhydramine are widely used to treat allergic conditions, such as urticaria and allergic rhinitis 5, 6.

Differences in Safety and Efficacy

  • Newer generation antihistamines, such as loratadine and fexofenadine, have been shown to be safer and more effective than first-generation antihistamines like chlorpheneramine and diphenhydramine 3, 5.
  • Chlorpheneramine has been reported to have a wider range of clinical applications, including treating asthma, plasma cell gingivitis, and depression, among others 6.
  • Diphenhydramine has been shown to have a faster onset of action compared to some newer antihistamines, but it also has a higher incidence of sedation 3.

Clinical Applications and Potential

  • Chlorpheneramine has been explored for its potential use in treating COVID-19 due to its antiviral properties against SARS-CoV-2 6.
  • Diphenhydramine is commonly used to treat acute allergic reactions, but its use is often limited due to its sedative effects 3.
  • Both chlorpheneramine and diphenhydramine have been used for decades to treat various allergic conditions, but their safety and efficacy profiles differ significantly from newer generation antihistamines 2, 5.

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.