Two medicines, side by side
Diphenhydramine vs pseudoephedrine
Diphenhydramine and pseudoephedrine are both labeled for cough and cold. Drugs@FDA records approvals of diphenhydramine since 1946 and of pseudoephedrine since 1975. Pharmacies paid $0.898 per mL (Diphenhydramine 50 mg/mL vial) and $0.281 per pseudoephedrine ER 120 mg tablet (NADAC, October 7, 2026); the strengths differ, so the two prices are not like for like. In FDA's classes, diphenhydramine is a histamine-1 receptor antagonist and pseudoephedrine an alpha-adrenergic agonist.
Check it at the source: the diphenhydramine FDA label on DailyMed (effective November 18, 2025); the pseudoephedrine FDA label on DailyMed (effective October 30, 2025).
Highlights of the diphenhydramine record
Diphenhydramine (Benadryl) · label of November 18, 2025
Used for
From the label: indicationsDiphenhydramine hydrochloride injection, USP is effective in adults and pediatric patients, other than premature infants and neonates, for the following conditions when the oral form is impractical. […]
On the market
- Earliest approval on file
- March 4, 1946
- Generic labelers
- 20 labelers
- Pharmacy cost
- $0.898 per mL
Supply and safety
- Shortage
- No current entry
- Recalls
- 8
Highlights of the pseudoephedrine record
Pseudoephedrine (Novafed) · label of October 30, 2025
Used for
From the label: indications• temporarily relieves nasal congestion due to the common cold, hay fever or other upper respiratory allergies • temporarily relieves sinus congestion and pressure
On the market
- Earliest approval on file
- August 29, 1975
- Generic labelers
- 34 labelers
- Pharmacy cost
- $0.281 per tablet
Supply and safety
- Shortage
- No current entry
- Recalls
- 3
Source: FDA drug labels via openFDA (Diphenhydramine label of November 18, 2025, Pseudoephedrine label of October 30, 2025); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)
How do diphenhydramine and pseudoephedrine differ on the record?
In FDA's classes, diphenhydramine is a histamine-1 receptor antagonist and pseudoephedrine an alpha-adrenergic agonist.
Generics: diphenhydramine since 1972; pseudoephedrine since 1991 (Drugs@FDA).
| Diphenhydramine | Pseudoephedrine | |
|---|---|---|
| Labeled for | Cough and cold, Allergies, Pain | Cough and cold |
| Pharmacologic class | Histamine-1 Receptor Antagonist | alpha-Adrenergic Agonist |
| How it works (label) | n/a | n/a |
| Half-life (label) | n/a | n/a |
| Earliest approval on file (Drugs@FDA) | March 4, 1946 | August 29, 1975 |
| First generic approved | May 9, 1972 | October 31, 1991 |
| Generic labelers (NDC) | 20 labelers | 34 labelers |
| Pharmacy cost (NADAC, each one's most listed form; strengths differ) | $0.898 per mL (Diphenhydramine 50 mg/mL vial) | $0.281 per tablet (Pseudoephedrine ER 120 mg tablet) |
| 12-month price change | +0.8% | +5% |
| Boxed warning | No | No |
| Shortage now | No current entry | No current entry |
| Recalls recorded | 8 | 3 |
| FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used) | 164,832 | 11,123 |
| DEA schedule | none | none |
Source: Drugs@FDA, FDA NDC Directory, CMS NADAC of October 7, 2026, FDA shortages and recalls, FAERS via openFDA (FDA files October 8, 2026)
What next?
- Alternatives to diphenhydramine
- every medicine labeled for the same conditions