Antihistamines: Which to Choose and Which Makes You Drowsy

If you’re looking for an antihistamine for hay fever or an allergy, the useful question isn’t which is strongest but which lets you carry on with your day. Everything sold in a pharmacy blocks the same receptor — histamine H1 — and relieves sneezing, itching, a clear runny nose and watery eyes with broadly similar effectiveness. What differs between them is how much they cross the barrier protecting the brain, and therefore how drowsy they make you, what they interact with, and when you should take them.

First and second generation: the only division that matters

First-generation antihistamines — dexchlorpheniramine, chlorphenamine, diphenhydramine, hydroxyzine — are older molecules that get into the central nervous system easily. There they block histamine receptors that have nothing to do with your allergy, and the result is sedation. The product information for dexchlorpheniramine puts it plainly: the most frequent adverse reaction is mild to moderate drowsiness, and the medicine can impair the mental or physical ability needed to drive or operate machinery.

Second-generation ones — cetirizine, loratadine, desloratadine, bilastine, ebastine, rupatadine — were designed specifically not to do that. They are more selective for peripheral receptors and penetrate the brain far less. In practice that means they relieve the same symptoms while leaving you awake.

There is no therapeutic advantage to feeling sleepy. If an antihistamine floors you, it isn’t “working harder”: it’s the wrong group for what you need.

What the product information says, ingredient by ingredient

These are the figures recorded in the product information authorised in Spain (available through CIMA, the AEMPS database) and in the European product information:

Active ingredient	Usual adult dose	Reported drowsiness	The detail that changes the outcome
Dexchlorpheniramine	2 mg, 3-4 times a day (max. 12 mg/day)	Its most frequent adverse reaction	Amplified by alcohol and other CNS depressants; tolerated worse from age 60
Cetirizine	10 mg once a day	9.6% versus 5.0% on placebo	Needs a dose adjustment in kidney impairment
Loratadine	10 mg once a day	1.2% above placebo	Lower starting dose in severe liver impairment
Desloratadine	5 mg once a day	No excess over placebo	Active metabolite of loratadine
Bilastine	20 mg once a day	3.06% versus 2.86% on placebo	Loses 30% of its bioavailability with food or juice

A nuance on cetirizine: although its drowsiness figure is the highest of the second generation, the product information itself specifies that it was mild or moderate in most cases and that objective testing showed no relevant effects on driving, sleep latency or motor response at the 10 mg dose. In other words: more people notice it, but it is not equivalent to the sedation of a first-generation drug.

The costliest mistake: taking bilastine with breakfast

Of all the details on this list, this is the one that ruins a course of treatment most often. Bilastine is absorbed less well on a full stomach: food reduces its oral bioavailability by 30%, and grapefruit juice does exactly the same — an effect that can occur with other fruit juices too. That is why its product information says to take it one hour before or two hours after eating or drinking juice.

Someone taking the tablet with their coffee and toast is in practice receiving a reduced dose, and concludes that “bilastine doesn’t work for me”. It usually does; what’s wrong is the timing.

The others behave differently. Loratadine can be taken with or without food. With cetirizine, food doesn’t reduce how much is absorbed, it only delays it slightly.

Alcohol, driving, and the triangle on the box

With the first generation, alcohol and other central nervous system depressants amplify the sedation, and the official recommendation is to avoid taking them together.

With the second generation the picture is different but not naive. For cetirizine, no clinically significant interaction with alcohol has been demonstrated at therapeutic doses, though caution is advised; in sensitive people, combining alcohol or any CNS depressant can indeed reduce alertness. With loratadine, no potentiating effects were seen in psychomotor behaviour studies. With bilastine, psychomotor performance after alcohol was similar to alcohol with placebo.

In Spain, any medicine that can affect driving carries a pictogram on the carton: a red triangle with a black car and the wording “Conducción: ver prospecto” (driving: see the leaflet), required by Royal Decree 1345/2007. It doesn’t forbid you from driving; it is telling you to read that section of the leaflet before you get in the car. Worth knowing if you are buying medicine in a Spanish pharmacy and the packaging is unfamiliar.

Five things worth knowing before you start

1. If you’re going to have allergy testing, say so. Antihistamines block the skin reaction and distort the result. Cetirizine’s product information specifies a 3-day washout; loratadine’s, stopping at least 48 hours beforehand.
2. Stopping cetirizine can bring on itching or hives, even if you didn’t have them before you started. They are sometimes intense enough to force a restart of treatment, and usually settle once it resumes.
3. Kidney function matters for some and not others. Cetirizine is cleared mainly by the kidney and its dose is adjusted to creatinine clearance; it is contraindicated below 10 ml/min. Loratadine and bilastine need no such adjustment in adults.
4. Pregnancy and breastfeeding are not self-service. The product information asks for caution or advises against use depending on the drug and the stage, so that decision is made with a professional, not in the pharmacy aisle.
5. If you’re no better in 7 days, rethink it. Loratadine’s product information sets that window for reassessing the clinical picture. Stringing together weeks of antihistamine with no response is a sign the diagnosis may not be what you think.

When to see a doctor

An over-the-counter antihistamine covers mild, predictable allergy symptoms. Seek medical attention — urgently, in the first three cases — if you get:

• Difficulty breathing, wheezing, a feeling that your throat is closing, or a change in your voice. This can be anaphylaxis, and it is not treated with an allergy tablet.
• Swelling of the lips, tongue, eyelids or face, especially if it progresses quickly or comes with dizziness or vomiting.
• Hives with fever, joint pain or feeling generally unwell, or hives that leave a dark mark as they fade.
• Symptoms that don’t improve after a week of correct treatment, or that get worse.
• Hives lasting more than six weeks: that is chronic urticaria and needs assessment, not indefinite self-medication.
• Persistent nasal congestion with thick, one-sided discharge, facial pain or a lasting loss of smell: that doesn’t fit a simple allergy.
• Needing the antihistamine almost every day for months to feel well.
• If you have epilepsy, narrow-angle glaucoma, an enlarged prostate, urinary retention, arrhythmias or a history of long QT, or take long-term medication: check before starting, because several of these appear explicitly as precautions in the product information.

This article is general information and does not replace assessment by a healthcare professional. Always read the leaflet that comes with your medicine and ask your doctor or pharmacist if anything is unclear. Sources: Product information, cetirizine 10 mg (CIMA, AEMPS, in Spanish) · Product information, loratadine 10 mg (CIMA, AEMPS, in Spanish) · Product information, bilastine 20 mg (CIMA, AEMPS, in Spanish) · Product information, dexchlorpheniramine 2 mg (CIMA, AEMPS, in Spanish) · Desloratadine product information (EMA) · Medicines and driving: the pictogram (AEMPS, in Spanish)