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Two medicines, side by side

Guaifenesin vs diphenhydramine

Guaifenesin and diphenhydramine are both labeled for cough and cold. Drugs@FDA records approvals of guaifenesin since 2002 and of diphenhydramine since 1946. Pharmacies paid $0.284 per ft mucus relief ER 600 mg tablet 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, guaifenesin is an expectorant and diphenhydramine a histamine-1 receptor antagonist.

Check it at the source: the guaifenesin FDA label on DailyMed (effective May 27, 2026); the diphenhydramine FDA label on DailyMed (effective November 18, 2025).

Highlights of the guaifenesin record

Guaifenesin (Mucinex) · label of May 27, 2026

Used for

From the label: indications

helps loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus and make coughs more productive

On the market

Earliest approval on file
July 12, 2002
Generic labelers
91 labelers
Pharmacy cost
$0.284 per tablet

Supply and safety

Shortage
No current entry
Recalls
6

Highlights of the diphenhydramine record

Diphenhydramine (Benadryl) · label of November 18, 2025

Used for

From the label: indications

Diphenhydramine 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 (Guaifenesin label of May 27, 2026, Diphenhydramine label of November 18, 2025); NDC Directory, Drugs@FDA, NADAC, FDA shortages and recalls (October 8, 2026)

How do guaifenesin and diphenhydramine differ on the record?

In FDA's classes, guaifenesin is an expectorant and diphenhydramine a histamine-1 receptor antagonist.

Generics: guaifenesin since 2011; diphenhydramine since 1972 (Drugs@FDA).

GuaifenesinDiphenhydramine
Labeled forCough and coldCough and cold, Allergies, Pain
Pharmacologic classExpectorantHistamine-1 Receptor Antagonist
How it works (label)n/an/a
Half-life (label)n/an/a
Earliest approval on file (Drugs@FDA)July 12, 2002March 4, 1946
First generic approvedNovember 23, 2011May 9, 1972
Generic labelers (NDC)91 labelers20 labelers
Pharmacy cost (NADAC, each one's most listed form; strengths differ)$0.284 per tablet (Ft mucus relief ER 600 mg tablet)$0.898 per mL (Diphenhydramine 50 mg/mL vial)
12-month price change-11%+0.8%
Boxed warningNoNo
Shortage nowNo current entryNo current entry
Recalls recorded68
FAERS reports (a report is not proof of cause; counts follow how widely a medicine is used)30,329164,832
DEA schedulenonenone

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 guaifenesin
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