Diphenhydramine Over-the-Counter Availability in the United States
Yes, diphenhydramine is widely available over-the-counter in the United States in more than 300 formulations, including oral tablets, capsules, liquid solutions, and topical creams, though this widespread availability is increasingly recognized as a public health concern. 1, 2
Current OTC Status and Formulations
- Diphenhydramine is sold without prescription in multiple forms: oral tablets, capsules, liquid solutions (25 mg/10 mL), and 2% topical gel formulations 3, 1
- The FDA-approved oral formulations are readily accessible in pharmacies and retail stores throughout the US 1
- No prescription is required for purchase, making it one of the most accessible antihistamines on the market 2, 4
Critical Safety Concerns with OTC Availability
The American Geriatrics Society explicitly identifies diphenhydramine as inappropriate for older adults due to delirium risk, urinary retention, impaired judgment, and recommends avoiding it in patients with cardiac arrhythmia, hypertension, bladder neck obstruction, glaucoma, or hyperthyroidism. 5
High-Risk Populations
- Older adults (≥65 years) should avoid diphenhydramine entirely—59% of elderly patients using OTC sleep aids were found to be taking potentially inappropriate diphenhydramine-containing products 4
- The American Academy of Sleep Medicine recommends against using diphenhydramine for insomnia treatment in adults due to unfavorable risk-benefit ratio 3
- Children are at risk for cognitive decline and excitability, with fatal toxicity reported even from topical application 3, 6
Cardiovascular and Systemic Risks
- Hypotension is a recognized adverse effect occurring through anticholinergic and antihistaminic properties 3, 5
- First-generation antihistamines like diphenhydramine cause sedation, impair driving ability, and lead to cognitive decline, particularly in elderly patients 3
- The European Society of Cardiology does not recommend diphenhydramine for any cardiovascular indication and notes it should be avoided in elderly patients with cardiovascular disease 5
Appropriate Limited Uses (When OTC Purchase Occurs)
Despite OTC availability, diphenhydramine should only be used in specific, limited clinical scenarios:
- Anaphylaxis adjunct only: 1-2 mg/kg per dose (maximum 50 mg) IV or oral, but epinephrine remains first-line treatment and diphenhydramine should never be used as monotherapy 5, 7
- Endoscopic sedation adjunct: 25-50 mg IV reduces requirements for meperidine and midazolam, but is not recommended as monotherapy due to unpredictable effects and cardiovascular risks 3, 5
- Pediatric allergic reactions: 1-2 mg/kg per dose (maximum 50 mg) with oral liquid preferred over tablets for faster absorption, but only for mild reactions—not anaphylaxis alone 7
Safer OTC Alternatives
Second-generation antihistamines such as loratadine, cetirizine, and fexofenadine are preferred for allergic conditions due to superior safety profiles without cardiovascular risks or sedation. 3, 5
- These alternatives are also available OTC and are more affordable with better tolerability 8
- Countries including Germany and Sweden have restricted access to first-generation antihistamines in favor of second-generation agents 2
Clinical Pitfall to Avoid
The widespread OTC availability creates a false perception of safety—patients and providers must understand that "over-the-counter" does not mean "safe for everyone." 2, 4 Many older adults are unaware of safety risks (only 38% of diphenhydramine users recognized risks versus 49% of non-users) 4. Healthcare providers should actively counsel against diphenhydramine use and recommend second-generation alternatives for most indications 2, 8.