From the FDA Drug Label
• do not take more than 6 doses in 24 hours • 10 mL (25 mg) to 20 mL (50 mg)
The maximum daily dose of Benadryl (diphenhydramine) is 300 mg for adults and children over 12 years of age, assuming the maximum dose of 50 mg per dose, and not exceeding 6 doses in 24 hours 1.
From the Research
Given the potential for serious side effects and the availability of safer alternatives, the use of Benadryl (diphenhydramine) should be avoided whenever possible, and its maximum daily dose should not be considered a standard recommendation. The most recent and highest quality study 2 suggests that diphenhydramine has a higher adverse side-effect profile, particularly among children and older adults, and that it is time to say a final goodbye to its use.
Key Considerations
- The study published in 2025 2 in The World Allergy Organization journal highlights the need to move away from diphenhydramine due to its side effects and the availability of safer, second-generation antihistamines.
- Another study from 2025 3 discusses the efficacy of rilzabrutinib in treating patients with moderate to severe chronic spontaneous urticaria refractory to H1-antihistamines, further indicating the limitations of traditional antihistamines like diphenhydramine.
- An earlier review from 2010 4 on the efficacy of topical antihistamines in relieving pruritus found mixed evidence, with only topical doxepin showing significant benefits, and lacking evidence for diphenhydramine.
Recommendations
- Avoid using Benadryl (diphenhydramine) whenever possible due to its potential for serious side effects 2.
- Consider safer, second-generation antihistamines for the management of allergic reactions and symptoms.
- Always follow the latest clinical guidelines and consult with a healthcare professional for personalized advice on medication use.