Sold as Banophen, Benadryl, Calagel Reformulated Jun 2019, Dermamycin, Diphedryl and 20 more.
Class: Antihistamines for topical use; Aminoalkyl ethers.
First FDA approval 03/04/1946: 80 years on the US market.
This grade answers one narrow question: how strong is the public evidence and safety record behind this drug, and how clean is its money trail and court record? It is not a verdict on whether the drug is right for you.
B
Score breakdown (84/100)
Safety ×35%
A
Evidence ×25%
F
Regulatory ×15%
A
Money & lawsuits ×15%
A
Options ×10%
A
Safety: 95
Death share in reports is near or below the FAERS average (1.4x)
Off-label use is among the five most-reported items: widely used beyond its approved evidence (-5)
Evidence: 46
131 randomized trials and 5 systematic reviews/meta-analyses indexed in PubMed
No Cochrane review found (-5)
Only 41% of completed registered trials posted results (-8)
Regulatory history: 97
Recalls since 2016: 0 Class I, 2 Class II, 0 Class III across 53 generic makers (-3)
Money & lawsuits: 100
Pharma paid doctors $0 tied to this drug last year: negligible
Not named in any pending federal MDL
Options: 100
Generic versions approved (53 applications)
17 same-class alternatives exist
What the FDA label says
Approved uses
Uses for the relief of occasional sleeplessness reduces time to fall asleep if you have difficulty falling asleep
Contraindications
None listed.
Warnings and precautions
Warnings Do not use for children under 12 years of age with any other product containing diphenhydramine, even one used on skin
Adverse reactions (label)
Not available.
Source: FDA SPL label for VICKS ZzzQuil NIGHTTIME SLEEP-AID Diphenhydramine HCl FREE OF (The Procter & Gamble Manufacturing Company), effective 20260908.
Full label on DailyMed.
Side-effect reports sent to the FDA
These are counts of reports people filed, not rates of harm. Anyone can file one, and nobody checks whether the drug was the cause. Millions of doses are taken for every report sent, so the useful part is how this drug compares with the average across all drugs.
140,596reports that mention this drug
140,401of those blame this drug, not another one the person was taking
70%of reports describe a serious outcome, such as a hospital stay (average for all drugs: 57%)
12.6%of reports include a death, from any cause (average for all drugs: 9.1%)
Source: the FDA's Adverse Event Reporting System (FAERS). Reports are voluntary and unverified. Drugs that are prescribed a lot, in the news, or in lawsuits attract more reports, so the percentages are compared with the whole database to correct for that partly, not fully.
Recalls and regulatory record
2recall actions on file
4 / 53brand / generic applications
0label changes since 2021
NoREMS program
Date
Class
Firm
Reason
04/2022
Class II
Mckesson Medical-Surgical Inc. Corporate Office
cGMP deviations: Temperature abuse
03/2021
Class II
Cardinal Health Inc.
CGMP Deviations: Intermittent exposure to temperature excursion during storage.
Class I = reasonable probability of serious harm. Class II = temporary or reversible harm. Class III = unlikely to harm. Most generic recalls are manufacturing or labeling defects for one lot, not a verdict on the molecule.
Evidence base
131randomized trials (PubMed)
5systematic reviews
1,259registered trials
41%of completed trials posted results
12%terminated or withdrawn
47%industry-funded
Counts measure how much evidence exists and how transparent it is, not how big the benefit is. For that, ask your prescriber: if 100 people like me took this, how many would get better because of it, and how many would be harmed? (Doctors call these the "number needed to treat" and "number needed to harm.") It differs by condition and is the number drug ads leave out. Sources: PubMed, ClinicalTrials.gov.
Money and lawsuits
In 2024, drug companies reported $0 in payments to US physicians and hospitals tied to this drug across 0 transactions.
No pending federal MDL names this drug or its brands.
Not named in any federal pharmaceutical settlement of $100M or more on record.
Sources: CMS Open Payments (Sunshine Act); Judicial Panel on Multidistrict Litigation pending docket list; DOJ settlements as tabulated on Wikipedia with links to the primary record. State-court and individual suits are not included.
Same ATC pharmacological class, graded ones first, best grade at the top. Being in the same class does not make them interchangeable for your condition; it makes them worth asking about.
Questions to ask your prescriber
The most-reported problems in FDA's adverse event data are fatigue, headache, nausea. How would we recognize and handle those?
Off-label use is among the most-reported items for this drug. Is my use on-label, and if not, what evidence supports it?
Why this one over bamipine, bromodiphenhydramine, carbinoxamine? What would make you pick one of those instead?
What result are we expecting, by when, and what is the plan if it does not happen?
If 100 people like me took this drug, how many would actually get better because of it, and how many would be harmed by it? (Doctors call these the number needed to treat and the number needed to harm.)