Antihistamine Side Effects by Type and How to Reduce Them

What you need to know

• Side effects depend heavily on whether an antihistamine is first- or second-generation.
• First-generation antihistamines (such as diphenhydramine) commonly cause sedation plus anticholinergic effects: dry mouth, blurred vision, constipation, urinary retention, and sometimes confusion.
• Second-generation antihistamines (loratadine, fexofenadine, cetirizine) have a much milder profile, though mild drowsiness, headache, fatigue, nausea, or dry mouth can still occur.
• Anticholinergic effects happen because first-generation antihistamines also block acetylcholine receptors, not just histamine receptors.
• Older adults are more sensitive to first-generation antihistamine effects, including confusion and fall risk, which is why they're generally advised to avoid them.
• Combining antihistamines with alcohol or other sedating substances increases drowsiness and impairment.

Side Effects by Generation

This is why second-generation antihistamines are generally preferred for regular or long-term use.

Why First-Generation Cause More Side Effects

First-generation antihistamines are fat-soluble and cross into the brain, producing drowsiness. They also block acetylcholine receptors throughout the body — so-called anticholinergic effects — which is what produces dry mouth, blurred vision, constipation, and difficulty urinating. Second-generation antihistamines were designed to be more selective for histamine receptors and to stay mostly out of the brain, which is why their side-effect profile is much milder.

Cautions for Older Adults

Older adults tend to clear first-generation antihistamines more slowly and are more sensitive to their anticholinergic and sedating effects, which can contribute to confusion, dizziness, and falls. For this reason, expert prescribing guidance for older adults generally advises against regular use of first-generation antihistamines like diphenhydramine and favors second-generation options. For more on this, see our allergies in older adults guide.

Reducing Your Risk of Side Effects

• Choose a second-generation antihistamine for regular or daytime use to minimize sedation and anticholinergic effects
• Use the lowest effective dose and follow label directions
• Avoid alcohol and other sedating substances, which add to drowsiness
• If you have glaucoma, an enlarged prostate, or urinary difficulty, ask a pharmacist or clinician before using a first-generation antihistamine
• For older adults, favor second-generation options and review antihistamine use with a clinician or pharmacist

First-generation antihistamines and children under 6

This is the sharpest safety line on the page, and it is easy to miss because these medicines are sold without a prescription and have been in family cupboards for decades.

The StatPearls review of antihistamines states that first-generation antihistamines should be avoided in children younger than 6, citing risks of respiratory depression and arrhythmias. That is a different order of concern from drowsiness, and it applies to the sedating older agents rather than to the newer non-drowsy ones.

It also rules out a practice that still circulates: using a sedating antihistamine to settle a young child, whether for sleep, for travel, or to get through a flight. Sedation is not the reason these medicines exist, and in this age group the risk is not worth it.

• Avoid first-generation (sedating) antihistamines in children under 6
• Never use one as a sleep aid or to calm a child, at any age, without medical advice
• Check the label for the active ingredient rather than going by the brand
• Ask a pharmacist which option suits your child's age — see our allergies in children guide
• Paediatric dosing is by weight and age, and this site does not provide doses

Older adults: what the formal guidance actually says

The caution for older adults is not informal advice. The StatPearls review notes that the 2024 American Geriatrics Society Beers Criteria classifies first-generation antihistamines as potentially inappropriate for older adults, and recommends second-generation antihistamines instead, with dose adjustments based on kidney function.

The stated reason is that older adults are at increased risk of adverse effects from anticholinergic and sedating first-generation antihistamines. Those effects compound existing risks rather than simply being unpleasant: confusion, blurred vision and dizziness in someone already unsteady is a falls risk, not just a side effect.

Two practical points follow. Being “potentially inappropriate” does not mean nobody over 65 may ever take one; it means the balance usually favours a second-generation alternative and that the choice deserves a conversation. And because dosing may need adjusting for kidney function, an over-the-counter purchase is not automatically the right dose for an older adult.

Impairment is more than feeling sleepy

Describing first-generation antihistamines as “drowsy” understates what they do. The StatPearls review describes psychomotor impairment among their effects, and explains the mechanism: these agents are highly lipophilic and readily cross the blood-brain barrier, engaging both central and peripheral H1 receptors and producing central nervous system effects.

That matters because psychomotor impairment and feeling sleepy are not the same measurement. Someone can judge that they no longer feel especially drowsy while reaction time and coordination are still affected, which is exactly the situation in which people decide they are fine to drive.

The review also notes that dizziness, tinnitus and delirium may occur at high doses, which is one reason taking extra for stubborn symptoms is a poor strategy. If a standard dose is not working, the answer is usually a different treatment approach rather than more of the same — see our guide to nasal sprays.

• Do not drive or operate machinery until you know how a sedating antihistamine affects you
• Feeling less drowsy is not proof that coordination and reaction time have recovered
• Effects can persist into the next day after a night-time dose
• Do not exceed the labelled dose to chase stubborn symptoms
• Alcohol and other sedating medicines add to the effect — see antihistamines and alcohol

When to seek care

Practical next steps

Safe general steps

1. Switch to a second-generation antihistamine if a first-generation one causes bothersome side effects
2. Use the lowest effective dose and read the label
3. Avoid alcohol and other sedating substances while taking antihistamines
4. Ask a pharmacist about interactions if you take other medications

Actions that need medical guidance

• Using antihistamines if you have glaucoma, an enlarged prostate, or urinary difficulty
• Choosing an antihistamine for an older adult
• Side effects that persist or interfere with daily life

Frequently asked questions

Sources

1. StatPearls (NCBI/NIH) — Antihistamines
2. Cleveland Clinic — Antihistamine Types & Side Effects
3. MedlinePlus (NIH/NLM) — Antihistamines for allergies

Medical disclaimer: This guide is for general education and isn't a substitute for personalized medical advice. It doesn't provide dosing. Always talk to a qualified healthcare professional about your symptoms and treatment.

Related guides