Two medicines, side by side
Acetaminophen vs diphenhydramine
Acetaminophen and diphenhydramine are both labeled for pain and cough and cold. Drugs@FDA records approvals of acetaminophen since 1968 and of diphenhydramine since 1946. Pharmacies paid $0.0339 per unit (Acetaminophen 500 mg caplet) 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. Only the acetaminophen label carries a boxed warning.
Check it at the source: the acetaminophen FDA label on DailyMed (effective November 13, 2024); the diphenhydramine FDA label on DailyMed (effective November 18, 2025).
Highlights of the acetaminophen record
Acetaminophen (Tylenol) · label of November 13, 2024
Used for
From the label: indicationstemporarily relieves minor aches and pains due to: minor pain of arthritis muscular aches backache premenstrual and menstrual cramps the common cold headache toothache temporarily reduces fever
On the market
- Earliest approval on file
- November 7, 1968
- Generic labelers
- 89 labelers
- Pharmacy cost
- $0.0339 per unit
Supply and safety
- Shortage
- No current entry
- Recalls
- 19
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 (Acetaminophen label of November 13, 2024, Diphenhydramine label of November 18, 2025); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)
How do acetaminophen and diphenhydramine differ on the record?
Only the acetaminophen label carries a boxed warning.
Generics: acetaminophen since 1986; diphenhydramine since 1972 (Drugs@FDA).
| Acetaminophen | Diphenhydramine | |
|---|---|---|
| Labeled for | Fever, Cough and cold, Pain | Cough and cold, Allergies, Pain |
| Pharmacologic class | n/a | 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) | November 7, 1968 | March 4, 1946 |
| First generic approved | December 1, 1986 | May 9, 1972 |
| Generic labelers (NDC) | 89 labelers | 20 labelers |
| Pharmacy cost (NADAC, each one's most listed form; strengths differ) | $0.0339 per unit (Acetaminophen 500 mg caplet) | $0.898 per mL (Diphenhydramine 50 mg/mL vial) |
| 12-month price change | +5% | +0.8% |
| Boxed warning | Yes | No |
| Shortage now | No current entry | No current entry |
| Recalls recorded | 19 | 8 |
| FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used) | 445,075 | 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 acetaminophen
- every medicine labeled for the same conditions