chlorpheniramine vs diphenhydramine
PlainMeds reviewed this comparison against our methodology in August 2026. It places FDA and CMS record fields side by side, without recommending either medication.
Side-by-side comparison of chlorpheniramine and diphenhydramine. Data from FDA drug databases (Orange Book, NDC Directory, recalls, shortages) covering 20,000+ approved drugs, plus CMS pricing; see our methodology.
Chlor-Trimeton
Benadryl
Chlorpheniramine is an antihistamine medicine. It helps relieve allergy symptoms.
Diphenhydramine, also known as Benadryl, is an antihistamine medicine. It helps relieve allergy and cold symptoms.
This medicine temporarily relieves symptoms from allergies or a cold. It can help with sneezing, runny nose, and itchy eyes. It also helps with itching of the nose or throat.
This medicine temporarily relieves symptoms from allergies or hay fever. These symptoms include sneezing, itchy nose or throat, runny nose, and itchy, watery eyes. It also helps with sneezing and runny nose caused by the common cold.
Chlorpheniramine blocks histamine, a natural substance your body makes during an allergic reaction. By blocking histamine, it reduces allergy symptoms. This medicine is a first-generation antihistamine.
Diphenhydramine blocks histamine, a natural substance that your body makes during an allergic reaction. By blocking histamine, it reduces allergy symptoms. It can also dry up nasal passages to relieve a runny nose.
- • Dizziness
- • Constipation
- • Headache
- • Fatigue
- • Nausea
- Nausea 601
- Diarrhoea 568
- Fatigue 467
- Dyspnoea 416
- Pyrexia 383
- Headache 5,138
- Fatigue 5,076
- Nausea 4,484
- Pain 4,014
- Sinusitis 3,668
No specific warnings noted.
No specific warnings noted.
If you are pregnant or breastfeeding, talk to your doctor before using this medicine. They can advise you on whether it is safe for you and your baby.
If you are pregnant or breastfeeding, talk to your doctor before using this medicine. It is important to weigh the benefits and risks with your doctor.
How to Read This chlorpheniramine vs diphenhydramine Comparison
chlorpheniramine is classified in the First-Generation Antihistamine drug class, while diphenhydramine sits within the First-Generation Antihistamine class. Because both drugs share the same classification, they are often considered interchangeable in theory, but clinical outcomes rarely track that cleanly. Both drugs are available over the counter.
Adverse event totals above are pulled from the FDA's Adverse Event Reporting System (FAERS). For these top-ranked reactions alone, chlorpheniramine has 2,435 submissions while diphenhydramine has 22,380. Those figures reflect cumulative reporting volume, not per-patient risk, so older, widely dispensed drugs typically look worse on count alone. No direct interaction between these two drugs is listed in our FDA-derived dataset, though co-prescription still warrants pharmacist review. Serious warnings, pregnancy guidance, and contraindications can differ even when indications overlap.
A table cannot represent individual circumstances. Data here is sourced from FDA Structured Product Labels (SPL) and FAERS, both of which update as manufacturers and clinicians submit new information. This registry does not provide medical, treatment, substitution, or medication-change directions for chlorpheniramine or diphenhydramine.
Registry boundary: This comparison displays source-record fields and does not provide individualized medical direction.