4.1. Therapeutic indications

Histallay 120 mg is indicated in adults and children 12 years and older for the relief of symptoms associated with allergic rhinitis.

4.2. Posology and method of administration

Posology

Adults

The recommended dose of fexofenadine hydrochloride for adults is 120 mg once daily taken before a meal. Fexofenadine is a pharmacologically active metabolite of terfenadine.

Paediatric population

▪ Children aged 12 years and over

The recommended dose of fexofenadine hydrochloride for children aged 12 years and over is 120 mg once daily taken before a meal.

▪ Children under 12 years of age

The efficacy and safety of fexofenadine hydrochloride has not been studied in children under 12.

Special populations

Studies in special risk groups (elderly, renally or hepatically impaired patients) indicate that it is not necessary to adjust the dose of fexofenadine hydrochloride in these patients.

4.3. Contraindications

The medicinal product is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

As with most new medicinal products there is only limited data in the elderly and renally or hepatically impaired patients. Histallay should be administered with care in these special groups on the advice of a doctor.

Patients with a history of or ongoing cardiovascular disease should be warned that, antihistamines as a medicine class, have been associated with the adverse reactions, tachycardia and palpitations (see section 4.8) and should use Histallay 120 mg only on the advice of their doctor.

Histallay 120 mg should not be used in children under 12 years of age.

In children from 6 to 11 years of age: fexofenadine hydrochloride 30 mg tablet (prescription only medicine) is the appropriate formulation for administration and dosing in this population.

Histallay 120 mg Film-Coated Tablets also contain Allura Red AC Lake, which may cause allergic reactions.

4.5. Interaction with other medicinal products and other forms of interaction

Fexofenadine does not undergo hepatic biotransformation and therefore will not interact with other medicinal products through hepatic mechanisms.

Fexofenadine is a P-glycoprotein (P-gp) and organic-anion-transporting polypeptide (OATP) substrate. Concomitant use of fexofenadine with P-gp inhibitors or inducers can affect the exposure to fexofenadine. Coadministration of fexofenadine hydrochloride with P-gp inhibitors erythromycin or ketoconazole has been found to result in a 2-3 times increase in the level of fexofenadine in plasma. The changes were not accompanied by any effects on the QT interval and were not associated with any increase in adverse reactions compared to the medicinal products given singly.

A clinical drug-drug interaction study showed that co-administration of apalutamide (a weak inducer of P-gp) and a single oral dose of 30 mg fexofenadine resulted in a 30 % decrease in AUC of fexofenadine.

No interaction between fexofenadine and omeprazole was observed. However, the administration of an antacid containing aluminium and magnesium hydroxide gels 15 minutes prior to fexofenadine hydrochloride caused a reduction in bioavailability, most likely due to binding in the gastrointestinal tract. It is advisable to leave 2 hours between administration of fexofenadine hydrochloride and aluminium and magnesium hydroxide containing antacids.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are no adequate data from the use of fexofenadine hydrochloride in pregnant women.

Limited animal studies do not indicate direct or indirect harmful effects with respect to effects on pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). Histallay 120 mg should not be used during pregnancy unless unless on the advice of a doctor.

Lactation

There are no data on the content of human milk after administering fexofenadine hydrochloride. However, when terfenadine was administered to nursing mothers fexofenadine was found to cross into human breast milk. Therefore Histallay is not recommended for mothers breastfeeding their babies. Breast-feeding women should only use Histallay 120 mg if advised to do so by a doctor.

Fertility

No human data on the effect of fexofenadine hydrochloride on fertility are available. In mice, there was no effect on fertility with fexofenadine hydrochloride treatments (see section 5.3).

4.7. Effects on ability to drive and use machines

On the basis of the pharmacodynamic profile and reported adverse reactions it is unlikely that fexofenadine hydrochloride tablets will produce an effect on the ability to drive or use machines.

In objective tests, fexofenadine hydrochloride has been shown to have no significant effects on central nervous system function. This means that patients may drive or perform tasks that require concentration. However, in order to identify sensitive people who have an unusual reaction to medicinal products, it is advisable to check the individual response before driving or performing complicated tasks.

4.8. Undesirable effects

The following frequency rating has been used, when applicable:

Very common ≥1/10;

Common ≥1/100 and <1/10;

Uncommon ≥1/1,000 and <1/100;

Rare ≥1/10,000 and <1/1,000;

Very rare <1/10,000

and not known (frequency cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

In adults, the following undesirable effects have been reported in clinical trials, with an incidence similar to that observed with placebo:

Nervous system disorders

Common: headache, drowsiness, dizziness

Eye disorders:

Not known: Vision blurred

Gastrointestinal disorders

Common: nausea

General disorders and administration site conditions

Uncommon: fatigue

In adults, the following undesirable effects have been reported in post-marketing surveillance. The frequency with which they occur is not known (cannot be estimated from available data):

Immune system disorders

hypersensitivity reactions with manifestations such as angioedema, chest tightness, dyspnoea, flushing and systemic anaphylaxis

Psychiatric disorders

insomnia, nervousness, sleep disorders or nightmares/excessive dreaming (paroniria)

Cardiac disorders:

tachycardia, palpitations

Gastrointestinal disorders

diarrhoea

Skin and subcutaneous tissue disorders

rash, urticaria, pruritus

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Dizziness, drowsiness, fatigue and dry mouth have been reported with overdose of fexofenadine hydrochloride. Single doses up to 800 mg and doses up to 690 mg twice daily for 1 month or 240 mg once daily for 1 year have been administered to healthy subjects without the development of clinically significant adverse reactions as compared with placebo. The maximum tolerated dose of fexofenadine hydrochloride has not been established.

Standard measures should be considered to remove any unabsorbed medicinal product. Symptomatic and supportive treatment is recommended. Haemodialysis does not effectively remove fexofenadine hydrochloride from blood.