Benadryl vs Hydroxyzine: Two Sedating Antihistamines, Different Jobs

Benadryl vs Hydroxyzine at a Glance

Doses above are from the current U.S. Drug Facts or prescribing labels listed in Sources. Always follow the label on the package you buy, because store brands and formulations differ.

Two Old-School Antihistamines

Both drugs are first-generation H1 antihistamines. Unlike newer allergy medicines such as cetirizine (Zyrtec), loratadine (Claritin) and fexofenadine (Allegra), they cross easily into the brain, which is why they cause drowsiness. They also block acetylcholine (anticholinergic effects), which causes dry mouth, constipation, urinary retention and, especially in older adults, confusion.

Hydroxyzine is chemically related to cetirizine; in fact, cetirizine is a metabolite of hydroxyzine. The hydroxyzine label contraindicates it in people with known hypersensitivity to cetirizine or levocetirizine for that reason.

What Each Is Labeled For

Benadryl

The Benadryl Allergy tablet label lists temporary relief of runny nose, sneezing, itchy watery eyes and itchy nose or throat due to hay fever or other upper respiratory allergies, and runny nose and sneezing due to the common cold. Diphenhydramine is also the active ingredient in many OTC nighttime sleep aids and in topical anti-itch products, which matters for avoiding accidental double dosing.

Hydroxyzine

The hydroxyzine hydrochloride label lists symptomatic relief of anxiety and tension associated with psychoneurosis and as an adjunct in organic disease states where anxiety is present; management of itching due to allergic conditions such as chronic urticaria (hives) and atopic and contact dermatoses; and use as a sedative before and after general anesthesia. The label notes that effectiveness as an anti-anxiety agent for long-term use (more than 4 months) has not been assessed in systematic clinical studies, and that a clinician should periodically reassess its usefulness.

In practice, hydroxyzine is prescribed for short-term or as-needed anxiety (it is not habit-forming like benzodiazepines), for itch that keeps people awake, and sometimes off-label for sleep.

Dosing

Benadryl (25 mg tablets), per Drug Facts: adults and children 12 and over take 1 to 2 tablets every 4 to 6 hours; children 6 to under 12 take 1 tablet; do not take more than 6 times in 24 hours; do not use in children under 6.

Hydroxyzine, per the prescribing information: for anxiety, adults 50 to 100 mg four times daily; for itching, adults 25 mg three or four times daily; with pediatric doses specified by age. Prescribers often start lower, particularly at bedtime, because of drowsiness. Hydroxyzine comes as hydroxyzine hydrochloride tablets and syrup and hydroxyzine pamoate capsules (Vistaril).

Safety Differences

Heart rhythm (hydroxyzine)

The hydroxyzine label warns that cases of QT prolongation and torsade de pointes have been reported, mostly in people with other risk factors such as heart disease, electrolyte imbalances or other QT-prolonging drugs. It is contraindicated in people with a prolonged QT interval, and caution is advised with congenital long QT syndrome, recent heart attack, uncompensated heart failure, slow heart rhythms and drugs known to prolong QT (certain antiarrhythmics, antipsychotics, antidepressants, antibiotics and others). Tell your prescriber about all medicines you take.

Pregnancy

The hydroxyzine label states that human data are inadequate to establish safety in early pregnancy and that hydroxyzine is contraindicated in early pregnancy. The Benadryl label tells pregnant or breastfeeding people to ask a health professional before use.

Older adults

The American Geriatrics Society Beers Criteria list first-generation antihistamines, including diphenhydramine and hydroxyzine, as potentially inappropriate for adults 65 and older because they are highly anticholinergic and can cause confusion, constipation, dry mouth and urinary retention, with reduced clearance in older age. Use as an occasional emergency treatment for a severe allergic reaction is a recognized exception.

Shared warnings

• Do not drive or operate machinery until you know how the drug affects you.
• Avoid alcohol, sedatives and tranquilizers, which increase drowsiness.
• Ask a doctor first if you have glaucoma, trouble urinating due to an enlarged prostate, or a breathing problem such as emphysema or chronic bronchitis (Benadryl label).
• Children may become excitable rather than drowsy (Benadryl label).
• Do not combine diphenhydramine products, including topical ones; the Benadryl label says not to use with any other diphenhydramine product, even one used on skin.

Hydroxyzine for Anxiety vs Benadryl for Sleep

People sometimes use OTC diphenhydramine for anxiety or sleep. It is not labeled for anxiety, and sedation is not the same as treating an anxiety disorder. The American Academy of Sleep Medicine’s guideline on medicines for chronic insomnia recommends against using diphenhydramine for that purpose, citing weak evidence and side effects. If anxiety or insomnia is ongoing, talk with a clinician about evidence-based treatments such as cognitive behavioral therapy and, when appropriate, medications designed for those conditions.

Which Makes Sense?

• Seasonal or indoor allergies: a non-drowsy antihistamine is usually a better daily choice than either; Benadryl is mainly useful short term.
• Itchy hives or eczema that disrupt sleep: a clinician may prescribe hydroxyzine; non-drowsy antihistamines are often used during the day.
• Short-term anxiety: hydroxyzine is a prescription option; Benadryl is not labeled for this.
• Age 65+, pregnant, or heart rhythm concerns: talk to your clinician before using either.

Both are inexpensive generics. Generic diphenhydramine contains the same active ingredient as Benadryl; OTC antihistamines are generally HSA/FSA-eligible under the CARES Act rules for OTC medicines, and hydroxyzine, as a prescription drug, is eligible when prescribed.

Overdose Risks and Children

Diphenhydramine is found in many products: allergy tablets, liquid allergy medicine for children, nighttime pain relievers (the “PM” products), sleep aids and anti-itch creams. Taking several at once is a common way people accidentally exceed the daily limit. High doses can cause agitation, hallucinations, seizures, a fast heart rate and dangerous heart rhythm problems. FDA has warned that taking higher than recommended doses of diphenhydramine can lead to serious heart problems, seizures, coma or death, after reports tied to social media challenges.

The Benadryl label says not to use it to make a child sleepy, and the tablet label says not to use it in children under 6. Hydroxyzine for children is dosed by a prescriber by age and weight. Store both out of reach, and call Poison Control (1-800-222-1222) for any suspected overdose.

When to Talk to Your Doctor or Pharmacist

Call 911 for signs of anaphylaxis: trouble breathing, throat tightness, swelling of the lips or tongue, fainting or widespread hives with dizziness. Antihistamines do not treat anaphylaxis; epinephrine does. Seek care for fainting, a racing or irregular heartbeat on hydroxyzine, severe confusion, inability to urinate, or if you suspect an overdose (call Poison Control at 1-800-222-1222).

Frequently Asked Questions

Sources

• DailyMed: Benadryl Allergy (diphenhydramine HCl 25 mg) Drug Facts
• DailyMed: Hydroxyzine hydrochloride tablets prescribing information
• PubMed: American Geriatrics Society 2023 updated AGS Beers Criteria
• PubMed: Sateia et al., AASM clinical practice guideline for pharmacologic treatment of chronic insomnia (2017)
• MedlinePlus: Hydroxyzine
• MedlinePlus: Diphenhydramine
• FDA: FDA warns about serious problems with high doses of the allergy medicine diphenhydramine (Benadryl)

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