Ilaxten Oral 2,5 mg Oral Solution

Symptomatic treatment of allergic rhino-conjunctivitis (seasonal and perennial) and urticaria in children aged 6 to 11 years with a body weight of at least 20 kg.

Posology

Paediatric population

Children 6 to 11 years of age with a body weight of at least 20 kg 10 mg bilastine (4 mL oral solution) once daily for the relief of symptoms of allergic rhino-conjunctivitis (seasonal allergic rhinitis and perennial allergic rhinitis) and urticaria. The oral solution should be taken one hour before or two hours after the intake of food or fruit juice (see section 4.5).

Children under 6 years of age and under 20 kg Currently available data are described in section 4.4, 4.8, 5.1 and 5.2 but no recommendation on a posology can be made. Therefore, ILAXTEN ORAL SOLUTION should not be used in this age group.

Duration of treatment

For allergic rhino-conjunctivitis the treatment should be limited to the period of exposure to allergens. For seasonal allergic rhinitis treatment could be discontinued after the symptoms have resolved and reinitiated upon their reappearance. In perennial allergic rhinitis continued treatment may be proposed to the patients during the allergen exposure periods. For urticaria the duration of treatment depends on the type, duration and course of the symptoms.

Special populations

Renal impairment The safety and efficacy of bilastine in renally impaired children have not been established. Studies conducted in adults in special risk groups (renally impaired patients) indicate that it is not necessary to adjust the dose of bilastine in adults (see section 5.2).

Hepatic impairment The safety and efficacy of bilastine in hepatically impaired children have not been established. There is no clinical experience in adult or paediatric patients with hepatic impairment. However, since bilastine is not metabolised and is eliminated as unchanged in urine and feces, hepatic impairment is not expected to increase systemic exposure above the safety margin in adult patients. Therefore, no dosage adjustment is required in adult patients with hepatic impairment (see section 5.2).

Paediatric population The safety and efficacy of ILAXTEN OS in children under the age of 6 years have not yet been established (see section 4.4).

Method of administration

Oral use. The bottle of oral solution is provided with a child-proof cap and must be opened as follows: press the plastic screwcap downwards and simultaneously turn anti-clockwise. The oral solution is accompanied by a measuring cup for dosage with a mark of 4 mL (10 mg bilastine per dosing).

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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, ciclosporin, ritonavir or diltiazem, may increase plasma 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.

ILAXTEN ORAL SOLUTION contains methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216) which may cause allergic reactions (possibly delayed).

ILAXTEN ORAL SOLUTION contains up to 0,44 mg of alcohol (ethanol) in each dose (4 mL) which is equivalent to 11 mg/100 mL (0,011 % w/v ). The amount in 4 mL of ILAXTEN ORAL SOLUTION is equivalent to less than 0,02 mL beer or 0,005 mL wine. The small amount of alcohol in ILAXTEN ORAL SOLUTION will not have any noticeable effects.

ILAXTEN ORAL SOLUTION contains less than 1 mmol sodium (23 mg) per 4 mL, that is to say essentially sodium free.

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

Food

Food significantly reduces the oral bioavailability of bilastine 20 mg tablets by 30 % and bilastine 2,5 mg/mL oral solution by 20 %.

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).

Medicines that are substrates or inhibitors of OATP1A2, such as ritonavir or rifampicin, may likewise have the potential to decrease plasma concentrations of bilastine.

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 to 3-fold. These changes can be explained by interaction with intestinal efflux transporters, since bilastine is a 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 medicines that are substrates or inhibitors of P-gp, such as ciclosporin, may likewise have the potential to increase plasma concentrations of bilastine.

Diltiazem

Concomitant intake of bilastine 20 mg and diltiazem 60 mg 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.

Alcohol

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

Lorazepam

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

Paediatric population

No interaction studies have been performed in children with bilastine oral solution. As there is no clinical experience regarding the interaction of bilastine with other medicines, 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 a limited amount of data from the use of bilastine in pregnant women. Animal studies did 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 ORAL SOLUTION during pregnancy.

Breastfeeding

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).

Fertility

There are no or a 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 bilastine did not affect driving performance. However, as the individual response to the medicines 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 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 post-marketing surveillance has confirmed clinical trial findings.

The percentage of children (2 u2013 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 u2013 11 years) receiving bilastine 10 mg (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

Adverse events at least possibly related to bilastine and reported in more than 0,1 % of children (2 u2013 11 years) receiving bilastine during the clinical development are tabulated below. Frequencies are assigned as follows: Very common (u2265 1/10) Common (u2265 1/100 to < 1/10) Uncommon (u2265 1/1 000 to < 1/100) Rare (u2265 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.

System Organ Class Frequency Adverse Reaction

Infections and infestations Common Rhinitis

Nervous system disorders Common Headache

Uncommon Dizziness

Loss of consciousness

Eye disorders Common Allergic conjunctivitis

Uncommon Eye irritation

Gastrointestinal disorders Common Abdominal pain / Upper abdominal pain

Uncommon Diarrhoea

Nausea

Lip swelling

Skin and subcutaneous tissue disorders Uncommon Eczema

Urticaria

General disorders and administration site conditions Uncommon Fatigue

Summary of safety profile in adult and adolescent patients

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 2 525 adult and adolescent patients treated with different doses of bilastine, of which 1697 received bilastine 20 mg. In these trials 1 362 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=1 697) are tabulated below. Frequencies are assigned as follows: Very common (u2265 1/10) Common (u2265 1/100 to < 1/10) Uncommon (u2265 1/1 000 to < 1/100) Rare (u2265 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.

System Organ Class Frequency Adverse reaction

Infections and infestations Uncommon Oral herpes

Metabolism and nutrition disorders Uncommon Increased appetite

Psychiatric disorders Uncommon Anxiety

Insomnia

Nervous system disorders Common Somnolence

Headache

Uncommon Dizziness

Ear and labyrinth disorders Uncommon Tinnitus

Vertigo

Cardiac disorders Uncommon Right bundle branch block

Sinus dysrhythmia

Electrocardiogram QT prolonged

Other ECG abnormalities

Respiratory, thoracic and mediastinal disorders Uncommon Dyspnoea

Nasal discomfort

Nasal dryness

Gastrointestinal disorders Uncommon Upper abdominal pain

Abdominal pain

Nausea

Stomach discomfort

Diarrhoea

Dry mouth

Dyspepsia

Gastritis

Skin and subcutaneous tissue disorders Uncommon Pruritus

General disorders and administration site conditions Uncommon Fatigue

Thirst

Improved pre-existing condition

Pyrexia

Asthenia

Investigations Uncommon Increased gamma-glutamyltransferase

Increased alanine aminotransferase

Increased aspartate aminotransferase

Increased blood creatinine

Increased blood triglicerides

Increased weight

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

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of ILAXTEN ORAL SOLUTION is important. It allows continued monitoring of the benefit/risk balance of ILAXTEN ORAL SOLUTION. Healthcare professionals are asked to report any suspected adverse reactions via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

There are no data for overdose in children. Information regarding acute overdose of bilastine is retrieved from the experience of clinical trials conducted during the development in adults and the post-marketing surveillance. In clinical trials, after administration of bilastine at doses 10 to 11 times the therapeutic dose (220 mg as single dose or 200 mg/day for 7 days) to 26 adult healthy volunteers, frequency of treatment emergent adverse events was two times higher than with placebo. The adverse reactions most frequently reported were dizziness, headache and nausea. No serious adverse events and no significant prolongation in the QTc interval were reported. The information collected in the post-marketing surveillance is consistent with that reported in clinical trials.

Critical evaluation of bilastineu2019s multiple dose (100 mg x 4 days) effect on ventricular repolarisation by a QT/QTc cross-over study involving 30 healthy adult volunteers did not show significant QTc prolongation. In the event of overdose symptomatic and supportive treatment is recommended. There is no known specific antidote for bilastine.