ILAXTEN Tablet Ref.[6522] Active ingredients: Bilastine

Paediatric population

Efficacy and safety of bilastine in children under 2 years of age have not been established and there is little clinical experience in children aged 2 to 5 years, therefore bilastine should not be used in these age groups.

In patients with moderate or severe renal impairment coadministration of bilastine with P-glycoprotein inhibitors, such as e.g, ketoconazole, erythromycin, cyclosporine, ritonavir or diltiazem, may increase plasmatic levels of bilastine and therefore increase the risk of adverse effects of bilastine. Therefore, coadministration of bilastine and P-glycoprotein inhibitors should be avoided in patients with moderate or severe renal impairment.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium free’.

Interaction studies have only been performed in adults and are summarised below.

Interaction with food

Food significantly reduces the oral bioavailability of bilastine by 30%.

Interaction with grapefruit juice

concomitant intake of bilastine 20 mg and grapefruit juice decreased bilastine bioavailability by 30%. This effect may also apply to other fruit juices. The degree of bioavailability decrease may vary between producers and fruits. The mechanism for this interaction is an inhibition of OATP1A2, an uptake transporter for which bilastine is a substrate (see section 5.2). Medicinal products that are substrates or inhibitors of OATP1A2, such as ritonavir or rifampicin, may likewise have the potential to decrease plasma concentrations of bilastine.

Interaction with ketoconazole or erythromycin

Concomitant intake of bilastine 20 mg o.d. and ketoconazole 400 mg o.d. or erythromycin 500 mg t.i.d. increased bilastine AUC 2-fold and C_max 2-3 fold. These changes can be explained by interaction with intestinal efflux transporters, since bilastine is substrate for P-gp and not metabolised (see section 5.2). These changes do not appear to affect the safety profile of bilastine and ketoconazole or erythromycin, respectively. Other medicinal products that are substrates or inhibitors of P-gp, such as cyclosporine, may likewise have the potential to increase plasma concentrations of bilastine.

Interaction with diltiazem

Concomitant intake of bilastine 20 mg o.d. and diltiazem 60 mg o.d. increased C_max of bilastine by 50%. This effect can be explained by interaction with intestinal efflux transporters (see section 5.2), and does not appear to affect the safety profile of bilastine.

Interaction with alcohol

The psychomotor performance after concomitant intake of alcohol and 20 mg bilastine o.d. was similar to that observed after intake of alcohol and placebo.

Interaction with lorazepam

Concomitant intake of bilastine 20 mg o.d. and lorazepam 3 mg o.d. for 8 days did not potentiate the depressant CNS effects of lorazepam.

Paediatric population

Interaction studies have only been performed in adults. As there is no clinical experience regarding the interaction of bilastine with other medicinal products, food or fruit juices in children, the results obtained in adult interactions studies should be at present taken into consideration when prescribing bilastine to children. There are no clinical data in children to state whether changes to the AUC or C_max due to interactions affect the safety profile of bilastine.

Pregnancy

There are no or limited amount of data from the use of bilastine in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity, parturition or postnatal development (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Ilaxten during pregnancy.

Breast-feeding

The excretion of bilastine in milk has not been studied in humans. Available pharmacokinetic data in animals have shown excretion of bilastine in milk (see section 5.3). A decision on whether to continue/discontinue breast-feeding or to discontinue/abstain from Ilaxten therapy must be made taking into account the benefit of breast-feeding for the child and the benefit of bilastine therapy for the mother.

Fertility

There are no or limited amount of clinical data. A study in rats did not indicate any negative effect on fertility (see section 5.3).

A study performed in adults to assess the effects of bilastine on the ability to drive demonstrated that treatment with 20 mg did not affect the driving performance. However, as the individual response to the medicinal product may vary, patients should be advised not to drive or use machines until they have established their own response to bilastine.

Summary of safety profile

The incidence of adverse events in adult and adolescent patients suffering from allergic rhinoconjunctivitis or chronic idiopathic urticaria treated with 20 mg bilastine in clinical trials was comparable with the incidence in patients receiving placebo (12.7% versus 12.8%).

The phase II and III clinical trials performed during the clinical development included 2525 adult and adolescent patients treated with different doses of bilastine, of which 1697 received bilastine 20 mg. In these trials 1362 patients received placebo. The ADRs most commonly reported by patients receiving 20 mg bilastine for the indication of allergic rhinoconjunctivitis or chronic idiopathic urticaria were headache, somnolence, dizziness, and fatigue. These adverse events occurred with a comparable frequency in patients receiving placebo.

Tabulated summary of adverse reactions in adult and adolescent patients

ADRs at least possibly related to bilastine and reported in more than 0.1% of the patients receiving 20 mg bilastine during the clinical development (N=1697) are tabulated below.

Frequencies are assigned as follows: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).

Rare, very rare and reactions with unknown frequency have not been included in the table.

Frequency not known (cannot be estimated from the available data): Palpitations, tachycardia, hypersensitivity reactions (such as anaphylaxis, angioedema, dyspnoea, rash, localised oedema/local swelling, and erythema), and vomiting have been observed during the post-marketing period.

Description of selected adverse reactions

Somnolence, headache, dizziness and fatigue were observed either in patients treated with bilastine 20 mg or with placebo. The frequency reported was 3.06 % vs. 2.86% for somnolence; 4.01% vs. 3.38% for headache; 0.83% vs. 0.59% for dizziness, and 0.83% vs. 1.32% for fatigue.

The information collected during the post-marketing surveillance has confirmed the safety profile observed during the clinical development.

Summary of safety profile in paediatric population

During the clinical development the frequency, type and severity of adverse reactions in adolescents (12 years to 17 years) were the same as observed in adults. The information collected in this population (adolescents) during the post-marketing surveillance has confirmed clinical trial findings.

The percentage of children (2-11 years) which reported adverse events (AEs) after treatment with bilastine 10 mg for allergic rhinoconjunctivitis or chronic idiopathic urticaria in a 12-week controlled clinical trial was comparable with patients receiving placebo (68.5% versus 67.5%).

The related AEs most commonly reported by 291 children (2-11 years) receiving bilastine (orodispersible tablet formulation) during clinical trials (#260 children exposed in the clinical safety study, 31 children exposed in the pharmacokinetic study) were headache, allergic conjunctivitis, rhinitis and abdominal pain. These related adverse events occurred with a comparable frequency in 249 patients receiving placebo.

Tabulated summary of adverse reactions in paediatric population

AEs at least possibly related to bilastine and reported in more than 0.1% of children (2-11 years) receiving bilastine during the clinical development are tabulated below.

Frequencies are assigned as follows: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).

Rare, very rare and reactions with unknown frequency have not been included in the table.

^# 260 children exposed in the clinical safety study, 31 children exposed in the pharmacokinetic study

Description of selected adverse reactions in paediatric population

Headache, abdominal pain, allergic conjunctivitis and rhinitis were observed either in children treated with bilastine 10 mg or with placebo. The frequency reported was 2.1% vs. 1.2% for headache; 1.0% vs. 1.2% for abdominal pain; 1.4% vs. 2.0% for allergic conjunctivitis, and 1.0% vs. 1.2% for rhinitis.

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.

Not applicable.