"I've been taking cetirizine but it's not working any more." It is one of the most common presentations at the pharmacy counter during hay fever season. The patient has been using the same second-generation antihistamine for weeks or even years, and their symptoms have broken through. They want something stronger, something different, or simply an explanation.

This is a conversation pharmacists are well placed to manage. The evidence supports several strategies before referral to a GP becomes necessary.

Why antihistamines appear to stop working

True pharmacological tolerance to antihistamines — where the drug loses its receptor-blocking effect over time — is debated in the literature. What patients experience as "tolerance" usually has one of several explanations:

Pollen count variation. A patient who was comfortable on cetirizine during a moderate pollen week may have breakthrough symptoms during a very high count. This is not treatment failure; it is a change in allergen load.

Inadequate dosing. Many patients take antihistamines reactively (after symptoms start) rather than prophylactically. Second-generation antihistamines work best when taken regularly throughout the season, ideally before pollen exposure begins each day.

Wrong antihistamine for the symptom profile. Some patients have predominantly nasal symptoms (rhinorrhoea, congestion); others have predominantly ocular symptoms (itching, watering). An oral antihistamine alone may not adequately control severe nasal congestion, which responds better to an intranasal corticosteroid.

Additional allergen exposure. A patient who developed symptoms to grass pollen may also be reacting to tree pollen, house dust mites, or other allergens that overlap seasonally.

The switching strategy

When a patient reports that their current antihistamine is no longer effective, pharmacists can work through a structured approach.

Step 1: Check adherence and technique

Before switching, confirm the patient is taking the antihistamine daily (not just on symptomatic days), at the correct dose, and at a consistent time. Morning dosing may be preferable for patients whose symptoms are worst during the day.

Step 2: Try a different second-generation antihistamine

According to NICE CKS, the three main second-generation (non-sedating) antihistamines available over the counter — cetirizine, loratadine, and fexofenadine — have broadly similar efficacy in clinical trials. However, individual response varies, and switching from one to another is a reasonable first step.

Fexofenadine is often the pharmacist's next choice for patients who have tried cetirizine, as it is the least likely to cause any sedation and has a clean side-effect profile. However, patients should be advised to take it with water — fruit juices (particularly grapefruit, orange, and apple) reduce its absorption by up to 36% by inhibiting OATP transporters.

Step 3: Add a topical treatment

If switching antihistamines alone does not achieve adequate control, adding a topical treatment is the next step. The options include:

Intranasal corticosteroid spray (e.g. beclometasone, fluticasone — both available OTC). This is the single most effective treatment for moderate-to-severe allergic rhinitis and controls nasal congestion, which oral antihistamines manage poorly. NICE CKS recommends intranasal corticosteroids as first-line for moderate-to-severe symptoms.

Antihistamine eye drops (e.g. sodium cromoglicate, azelastine — available OTC). For patients with predominantly ocular symptoms, topical eye drops provide targeted relief that oral antihistamines may not fully achieve.

Step 4: Consider updosing (GP territory)

The British Society for Allergy and Clinical Immunology (BSACI) guidelines note that updosing second-generation antihistamines to two or four times the standard dose can be effective in chronic urticaria. For allergic rhinitis, the evidence is less robust, and updosing beyond the licensed dose is a prescriber decision. Pharmacists should not recommend this OTC but can refer the patient to their GP with a note that updosing may be appropriate.

Step 5: Refer

Referral to a GP is appropriate when:

• Symptoms are not controlled despite a regular oral antihistamine plus an intranasal corticosteroid
• The patient requires oral corticosteroids for symptom control
• There is diagnostic uncertainty (is this allergic rhinitis, non-allergic rhinitis, or both?)
• The patient is interested in immunotherapy (desensitisation)

Practical tips for the pharmacy counter

• Timing matters. Patients should start their antihistamine before the pollen season begins, not wait for the first sneeze.
• Combination therapy is better than switching repeatedly. An oral antihistamine plus an intranasal steroid is more effective than cycling through different oral antihistamines alone.
• Nasal saline irrigation can be suggested as an adjunct — it is inexpensive, safe, and helps clear allergens from the nasal mucosa.
• Avoid first-generation antihistamines (chlorphenamine, promethazine) as regular hay fever treatment. They cause sedation, impair driving, and have anticholinergic effects. Their only advantage is speed of onset for acute episodes.

Patients can use PharmSee's pharmacy finder to locate pharmacies offering hay fever consultations, and the job listings page tracks pharmacist roles across England for professionals looking to work in allergy-focused services.

Key points

• "Tolerance" to antihistamines is usually explained by pollen variation, poor adherence, or inadequate symptom targeting
• Switching between cetirizine, loratadine, and fexofenadine is a reasonable first step
• Adding an intranasal corticosteroid is more effective than switching antihistamines alone
• Updosing beyond the licensed dose is a GP decision, not a pharmacy recommendation
• Refer when combination therapy (oral antihistamine + intranasal steroid) fails to control symptoms

Sources: NICE CKS (Allergic rhinitis), BNF (Antihistamines), BSACI (Rhinitis guidelines). Article reflects guidance current as of April 2026.