Two medicines, side by side
Dextromethorphan vs diphenhydramine
Dextromethorphan and diphenhydramine are both labeled for cough and cold. Pharmacies paid $0.122 per unit (Dextromethorphan 15 mg softgel) and $0.898 per mL (Diphenhydramine 50 mg/mL vial) (NADAC, October 7, 2026); the strengths differ, so the two prices are not like for like. In FDA's classes, dextromethorphan is a sigma-1 agonist and diphenhydramine a histamine-1 receptor antagonist.
Check it at the source: the dextromethorphan FDA label on DailyMed (effective August 27, 2026); the diphenhydramine FDA label on DailyMed (effective November 18, 2025).
Highlights of the dextromethorphan record
Dextromethorphan (Delsym) · label of August 27, 2026
Used for
From the label: indicationstemporarily relieves • cough due to minor throat and bronchial irritation as may occur with the common cold or inhaled irritants • the impulse to cough to help you get to sleep
On the market
- Earliest approval on file
- n/a
- Generic labelers
- 28 labelers
- Pharmacy cost
- $0.122 per unit
Supply and safety
- Shortage
- No current entry
- Recalls
- 0
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
Source: FDA drug labels via openFDA (Dextromethorphan label of August 27, 2026, Diphenhydramine label of November 18, 2025); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)
How do dextromethorphan and diphenhydramine differ on the record?
In FDA's classes, dextromethorphan is a sigma-1 agonist and diphenhydramine a histamine-1 receptor antagonist.
Generics: dextromethorphan none approved; diphenhydramine since 1972 (Drugs@FDA).
| Dextromethorphan | Diphenhydramine | |
|---|---|---|
| Labeled for | Cough and cold | Cough and cold, Allergies, Pain |
| Pharmacologic class | Sigma-1 Agonist, Uncompetitive N-methyl-D-aspartate Receptor Antagonist | Histamine-1 Receptor Antagonist |
| How it works (label) | n/a | n/a |
| Half-life (label) | n/a | n/a |
| Earliest approval on file (Drugs@FDA) | n/a | March 4, 1946 |
| First generic approved | none | May 9, 1972 |
| Generic labelers (NDC) | 28 labelers | 20 labelers |
| Pharmacy cost (NADAC, each one's most listed form; strengths differ) | $0.122 per unit (Dextromethorphan 15 mg softgel) | $0.898 per mL (Diphenhydramine 50 mg/mL vial) |
| 12-month price change | +13% | +0.8% |
| Boxed warning | No | No |
| Shortage now | No current entry | No current entry |
| Recalls recorded | 0 | 8 |
| FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used) | 8,389 | 164,832 |
| 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 dextromethorphan
- every medicine labeled for the same conditions