Clatexo

CHARACTERISTICS OF THE MEDICINAL PRODUCT

1. NAME OF THE MEDICINAL PRODUCT

Clatexo, 20 mg, tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 20 mg of bilastine (Bilastinum).
A full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet
Round, white or almost white, biconvex tablets with a diameter of about 7 mm.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Symptomatic treatment of allergic rhinitis and conjunctivitis (seasonal and perennial)
and urticaria.
Clatexo is indicated for use in adults and adolescents (12 years of age and older).

4.2 Posology and method of administration

Posology

Adults and adolescents (12 years of age and older)
20 mg of bilastine (1 tablet) once daily to relieve symptoms of allergic rhinitis and conjunctivitis (seasonal and perennial) and urticaria.
The tablet should be taken 1 hour before or 2 hours after meals or fruit juice consumption (see section 4.5).
Duration of treatment
In the case of allergic rhinitis and conjunctivitis, the treatment period should be limited to the period of exposure to allergens. In the case of seasonal allergic rhinitis, treatment can be discontinued after the symptoms have resolved and resumed after they recur.
In perennial allergic rhinitis, continuous treatment can be proposed to patients during periods of exposure to allergens. The duration of treatment for urticaria depends on the type, duration, and course of the condition.
Special populations
Elderly patients
There is no need to adjust the dosage in elderly patients (see sections 5.1 and 5.2).
Renal impairment
Studies conducted in adults, in special risk groups (patients with renal impairment), indicate that it is not necessary to adjust the dosage of Clatexo in adult patients with renal impairment (see section 5.2).
Hepatic impairment
There are no clinical studies in patients with hepatic impairment. However, since bilastine is not metabolized and is excreted unchanged in the urine and feces, it is not considered that hepatic impairment has an impact on increasing systemic exposure above the safety margin in adult patients. Therefore, no dose adjustment is required in patients with hepatic impairment (see section 5.2).
Children and adolescents

• Children aged 6 to 11 years with a body weight of at least 20 kg In this population, the following are suitable for use: bilastine in the form of 10 mg tablets that dissolve in the mouth and bilastine in the form of an oral solution 2.5 mg / ml.
• Children under 6 years of age and with a body weight below 20 kg Current data are presented in sections 4.4, 4.8, 5.1, and 5.2, but there are no dosage recommendations. Therefore, bilastine should not be used in this age group.

The safety and efficacy of bilastine in children with renal or hepatic impairment have not been established.

Method of administration

Oral administration.
The tablet should be swallowed with water.

4.3 Contraindications

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

• 6.1.

4.4 Special warnings and precautions for use

Cases of QT interval prolongation in the electrocardiogram have been reported in patients taking bilastine (see sections 4.8, 4.9, and 5.1). It is suspected that drugs that prolong the QT / QTc interval increase the risk of developing ventricular tachycardia of the Torsade de pointes type.
Therefore, caution should be exercised when administering bilastine to patients who have an increased risk of QT / QTc interval prolongation. This applies to patients with a history of cardiac arrhythmias, patients with hypokalemia, hypomagnesemia, hypocalcemia, patients with a diagnosed QT interval prolongation or significant bradycardia, patients taking other medicinal products that prolong the QT / QTc interval.
Children and adolescents
The efficacy and safety of bilastine have not been established in children under 2 years of age, and in children aged 2 to 5 years, clinical data are limited, so bilastine should not be used in these age groups.
In patients with moderate or severe renal impairment, concomitant administration of bilastine with P-glycoprotein inhibitors (P-gp), such as ketokonazole, erythromycin, cyclosporine, ritonavir, or diltiazem, may increase the plasma concentration of bilastine, thereby increasing the risk of adverse reactions to bilastine. Therefore, in patients with moderate or severe renal impairment, concomitant administration of bilastine with P-glycoprotein inhibitors should be avoided.
Clatexo contains sodium
The product contains less than 1 mmol of sodium (23 mg) per tablet, which means the product is considered "sodium-free".

4.5 Interaction with other medicinal products and other forms of interaction

Interaction studies were conducted only in adults, and their results are presented below.
Food interactions: Food significantly reduces the bioavailability of bilastine after oral administration by 30%.
Grapefruit juice interactions: Concomitant administration of 20 mg of bilastine and grapefruit juice reduces the bioavailability of bilastine by 30%. This effect may apply to other fruit juices.
The degree of reduction in bioavailability may vary depending on the manufacturer and fruit.
The mechanism of this interaction is the inhibition of the OATP1A2 polypeptide, a uptake transporter for which bilastine is a substrate (see section 5.2). Medicinal products that are substrates or inhibitors of OATP1A2, such as ritonavir and rifampicin, may similarly reduce bilastine plasma concentrations.
Interactions with ketokonazole or erythromycin: Concomitant administration of 20 mg of bilastine once daily and 400 mg of ketokonazole once daily or 500 mg of erythromycin three times daily increases the systemic exposure (AUC) twofold and the maximum plasma concentration of bilastine (C) two to three times.
These changes can be explained by an interaction with intestinal efflux transporters, as bilastine is a substrate for P-glycoprotein and is not metabolized (see section 5.2). These changes do not appear to affect the safety profile of bilastine and ketokonazole or erythromycin. Other medicinal products that are substrates or inhibitors of P-glycoprotein, such as cyclosporine, may increase the plasma concentration of bilastine.
Interactions with diltiazem: Concomitant administration of 20 mg of bilastine once daily and 60 mg of diltiazem once daily increases the maximum plasma concentration of bilastine (C) by 50%. This effect can be explained by an interaction with intestinal efflux transporters (see section 5.2) and does not appear to affect the safety profile of bilastine.
Interactions with alcohol: Psychomotor performance after concomitant consumption of alcohol and 20 mg of bilastine once daily was similar to that observed after alcohol and placebo.
Interactions with lorazepam: Concomitant administration of 20 mg of bilastine once daily and 3 mg of lorazepam once daily for 8 days did not enhance the depressive effect of lorazepam on the central nervous system.
Children and adolescents
Interaction studies were conducted only in adults. Since there is limited clinical experience in children with interactions between bilastine and other medicinal products, food, and fruit juices, when prescribing bilastine to children, the results obtained in adult interaction studies should be taken into account. There are no clinical data in children to determine whether changes in AUC or C due to interactions affect the safety profile of bilastine.

4.6 Fertility, pregnancy and lactation

Pregnancy
There are no data or limited data on the use of bilastine in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity, pregnancy, parturition, or postnatal development (see section 5.3). As a precautionary measure, it is recommended to avoid the use of bilastine during pregnancy.
Breast-feeding
Bilastine has not been studied in human milk. Based on available pharmacokinetic data in animals, bilastine is excreted in milk (see section 5.3).
The decision to continue or stop breast-feeding or to continue or stop therapy with bilastine should be made taking into account the benefit of breast-feeding to the child and the benefit of bilastine therapy to the mother.
Fertility
There are no clinical data or limited clinical data. A study in rats did not show any negative effect on fertility (see section 5.3).

4.7 Effects on ability to drive and use machines

A study conducted in adults to assess the effect of bilastine on the ability to drive vehicles showed that taking bilastine at a dose of 20 mg did not affect the ability to drive vehicles. However, individual reactions to treatment may vary, so patients should be advised not to drive vehicles or operate machinery until they have verified their reaction to bilastine.

4.8 Undesirable effects

Summary of the safety profile in adult and adolescent patients
The frequency of adverse reactions in adults and adolescents with allergic rhinitis and conjunctivitis or chronic idiopathic urticaria treated with 20 mg of bilastine in clinical studies was comparable to the frequency in patients taking placebo (12.7% versus 12.8%).
Clinical studies of phase II and III conducted during the clinical development included 2525 adult and adolescent patients treated with bilastine at various doses, of which 1697 received bilastine at a dose of 20 mg. In these studies, 1362 patients received placebo. The most common adverse reactions reported by patients taking 20 mg of bilastine in the indication of allergic rhinitis and conjunctivitis and chronic idiopathic urticaria were headache, somnolence, dizziness, and fatigue. These adverse reactions occurred with a comparable frequency in patients taking placebo.
Tabular summary of adverse reactions in adult and adolescent patients
Adverse reactions that were at least possibly related to bilastine and reported in more than 0.1% of patients taking 20 mg of bilastine during clinical development (N = 1697) are listed below.
Frequencies are classified as follows:
very common (≥1/10)
common (≥1/100 to <1>uncommon (≥1/1,000 to <1>rare (≥1/10,000 to <1>very rare (<1>not known (frequency cannot be estimated from the available data)
Reactions that are rare, very rare, and of unknown frequency are not included in the table.

Bilastine regardless of

Classification of systems and organs

Bilastine 20 mg Placebo

N = 1362

Frequency Adverse reaction

Infections and infestations

Uncommon
Oral herpes
2 (0.12%)
2 (0.08%)
0 (0.0%)

N = 1697 doses

N = 2525

2 (0.12%)
2 (0.08%)
0 (0.0%)

Metabolism and nutrition disorders

Uncommon
Increased appetite
10 (0.59%)
11 (0.44%)
7 (0.51%)

Psychiatric disorders

Uncommon
Anxiety
6 (0.35%)
8 (0.32%)
0 (0.0%)
Insomnia
2 (0.12%)
4 (0.16%)
0 (0.0%)

Nervous system disorders

Common
Somnolence
52 (3.06%)
82 (3.25%)
39 (2.86%)
Headache
68 (4.01%)
90 (3.56%)
46 (3.38%)
Uncommon
Dizziness of central origin
14 (0.83%)
23 (0.91%)
8 (0.59%)

Ear and labyrinth disorders

Uncommon
Tinnitus
2 (0.12%)
2 (0.08%)
0 (0.0%)
Dizziness of peripheral origin
3 (0.18%)
3 (0.12%)
0 (0.0%)

Cardiac disorders

Uncommon
Right bundle branch block
4 (0.24%)
5 (0.20%)
3 (0.22%)
Atrial arrhythmia
5 (0.30%)
5 (0.20%)
1 (0.07%)
QT interval prolongation in the electrocardiogram*
9 (0.53%)
10 (0.40%)
5 (0.37%)

*Cases of QT interval prolongation in the electrocardiogram have also been reported after the product was placed on the market.
Frequency not known (cannot be estimated from the available data):
palpitations, tachycardia, hypersensitivity reactions (e.g., anaphylactic reaction, angioedema, dyspnea, rash, local edema, and flushing) and vomiting have been observed during the post-marketing period.
Description of selected adverse reactions in adult and adolescent patients
In patients receiving bilastine at a dose of 20 mg or placebo, the following were reported: somnolence, headache, dizziness, and fatigue. The frequency of their occurrence for bilastine and placebo was 3.06% compared to 2.86% in the case of somnolence, 4.01% compared to 3.38% in the case of headache, 0.83% compared to 0.59% in the case of dizziness, and 0.83% compared to 1.32% in the case of fatigue.
Information collected during post-marketing surveillance confirmed the safety profile observed during clinical development.
Summary of the safety profile in children and adolescents
During clinical development, the frequency, type, and severity of adverse reactions in adolescents (12-17 years old) were the same as in adults. Information collected in this population (adolescents) during post-marketing surveillance confirmed the results of clinical studies.
The percentage of children (2-11 years old) treated for allergic rhinitis and conjunctivitis or chronic idiopathic urticaria who reported adverse reactions after taking bilastine at a dose of 10 mg in a 12-week controlled clinical study was comparable to the percentage of patients in the placebo group (68.5% versus 67.5%).
The most common adverse reactions reported by 291 children (2-11 years old) taking bilastine (in the form of orally disintegrating tablets) in the clinical study (#260 children participating in the safety study, 31 children participating in the pharmacokinetic study) were headache, allergic conjunctivitis, rhinitis, and abdominal pain. These adverse reactions occurred with a similar frequency in 249 patients taking placebo.
Tabular summary of adverse reactions in children and adolescents
Adverse reactions that were at least possibly related to bilastine and reported in more than 0.1% of children (2-11 years old) taking bilastine during clinical development are presented in the table below.
Frequencies are classified as follows:
very common (≥1/10)
common (≥1/100 to <1>uncommon (≥1/1,000 to <1>rare (≥1/10,000 to <1>very rare (<1>not known (frequency cannot be estimated from the available data)
Reactions that are rare, very rare, and of unknown frequency are not included in the table.

Classification of systems and organs Bilastine 10 mg (n = 291)

Placebo (n = 249)

Frequency Adverse reaction

Infections and infestations

Common
Rhinitis
3 (1.0%)
3 (1.2%)

Nervous system disorders

Common
Headache
6 (2.1%)
3 (1.2%)
Uncommon
Dizziness of central origin
1 (0.3%)
0 (0.0%)
Loss of consciousness
1 (0.3%)
0 (0.0%)

Eye disorders

Common
Allergic conjunctivitis
4 (1.4%)
5 (2.0%)
Uncommon
Eye irritation
1 (0.3%)
0 (0.0%)

Gastrointestinal disorders

Common
Abdominal pain, upper abdominal pain
3 (1.0%)
3 (1.2%)
Uncommon
Diarrhoea
2 (0.7%)
0 (0.0%)
Nausea
1 (0.3%)
0 (0.0%)
Lip swelling
1 (0.3%)
0 (0.0%)

Skin and subcutaneous tissue disorders

Uncommon
Rash
1 (0.3%)
0 (0.0%)
Urticaria
2 (0.7%)
2 (0.8%)

General disorders and administration site conditions

Uncommon
Fatigue
2 (0.7%)
0 (0.0%)
260 children participating in the safety study, 31 children participating in the pharmacokinetic study
Description of selected adverse reactions in children and adolescents
In children taking bilastine at a dose of 10 mg or placebo, the following were reported: headache, abdominal pain, allergic conjunctivitis, and rhinitis. The frequency of their occurrence for bilastine and placebo was 2.1% compared to 1.2% in the case of headache, 1.0% compared to 1.2% in the case of abdominal pain, 1.4% compared to 2.0% in the case of allergic conjunctivitis, and 1.0% compared to 1.2% in the case of rhinitis.
Reporting of suspected adverse reactions
After the product has been placed on the market, it is important to report suspected adverse reactions. This allows for continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.

4.9 Overdose

Information on acute overdoses of bilastine comes from experiences in clinical studies conducted during development and post-marketing surveillance. In clinical studies, after administration of bilastine in doses 10 to 11 times higher than the therapeutic dose (220 mg single dose or 200 mg per day for 7 days) to 26 healthy adult volunteers, the frequency of adverse reactions was twice as high as with placebo. The most commonly reported adverse reactions were dizziness, headache, and nausea. No serious adverse reactions or significant QTc interval prolongation were observed. Information collected during post-marketing surveillance is consistent with that reported in clinical studies.
A critical analysis of the effect of multiple doses of bilastine (100 mg x 4 days) on repolarization in a "detailed crossover QT / QTc interval study" in 30 healthy adult volunteers did not show significant QTc interval prolongation.
There are no data on overdoses in children.
In the event of an overdose, symptomatic and supportive treatment is recommended.
There is no specific antidote for bilastine.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Therapeutic category: systemic antihistamines, other systemic antihistamines, ATC code R06AX29.
Mechanism of action
Bilastine does not have sedative properties. It is a long-acting histamine antagonist with selective affinity for peripheral H1 receptors, which does not show affinity for muscarinic receptors.
Bilastine inhibits histamine-induced wheal and flare response on the skin for 24 hours after administration of a single dose.
Clinical efficacy and safety
In clinical studies conducted in adult and adolescent patients with allergic rhinitis and conjunctivitis (seasonal and perennial), bilastine at a dose of 20 mg once daily for 14-28 days effectively relieved symptoms such as sneezing, nasal discharge, nasal itching, nasal congestion, ocular itching, lacrimation, and ocular redness.
Bilastine effectively controlled symptoms for 24 hours.
In two clinical studies in patients with chronic idiopathic urticaria, bilastine at a dose of 20 mg once daily for 28 days effectively relieved symptoms such as pruritus intensity, number and size of wheals, and patient discomfort due to urticaria.
In these patients, an improvement in sleep quality and quality of life was also observed.
Clinical studies of bilastine did not show any significant QTc interval prolongation or other effects on the cardiovascular system, even after administration of a dose of 200 mg per day (10 times the clinical dose) to 9 patients for 7 days, as well as after concomitant administration of bilastine with P-glycoprotein inhibitors, such as ketokonazole (24 patients) and erythromycin (24 patients).
Additionally, a thorough QT interval study was conducted in 30 volunteers.
In controlled clinical studies at the recommended dose of 20 mg once daily, the safety profile of bilastine in relation to the central nervous system was similar to that of placebo, and the frequency of somnolence did not differ statistically from placebo. Bilastine at a dose of up to 40 mg once daily did not affect psychomotor performance in clinical studies or the ability to drive vehicles during a standard driving test.
Clinical studies of phase II and III did not show any differences in efficacy and safety in elderly patients (≥65 years) compared to younger patients. A post-marketing study in which 146 elderly patients participated did not show any differences in the safety profile compared to adults.
Children and adolescents
Clinical studies included adolescents (12-17 years old). During clinical studies, 128 adolescents received bilastine (81 adolescents in a double-blind study in the case of allergic rhinitis and conjunctivitis), and 116 adolescents were randomly assigned to the comparator or placebo group. No difference was found in efficacy and safety between adults and adolescents.
In accordance with the guidelines, the proven efficacy in adults and adolescents can be extrapolated to children if it is shown that the systemic exposure to bilastine at a dose of 10 mg in children aged 6-11 years with a body weight of at least 20 kg is equivalent to the exposure to bilastine at a dose of 20 mg in adults (see section 5.2). Extrapolation of data from adults and adolescents is appropriate for this medicinal product, as the pathophysiology of allergic rhinitis and conjunctivitis and urticaria is the same in all age groups.
In a 12-week controlled clinical study in children aged 2-11 years (a total of 509 children, 260 treated with bilastine at a dose of 10 mg: 58 aged 2 to <6 years, 105 aged 6 to <9 and 97 9 <12 249 treated with placebo: 58 2 <6 95 96 years), in which bilastine was administered at a dose of 10 mg once daily, the safety profile (n=260) similar that placebo 249), adverse reactions were reported 5.8% patients taking 8.0% placebo. both case placebo, slight decrease sedation sleepiness index according paediatric sleep questionnaire observed, non-significant statistical differences between groups. these children 2-11 no significant observed qtc interval after administration compared quality life for allergic conjunctivitis rhinitis or chronic urticaria showed overall improvement (according points) 12 weeks without arms.
A total of 509 children were included in the study: 479 children with allergic rhinitis and conjunctivitis and 30 children with diagnosed chronic urticaria. 260 children received bilastine, 252 (96.9%) with allergic rhinitis and conjunctivitis, and 8 (3.1%) with chronic urticaria. Similarly, 249 children received placebo, 227 (91.2%) with allergic rhinitis and conjunctivitis, and 22 (8.8%) with chronic urticaria.
The European Medicines Agency has waived the obligation to submit the results of studies with bilastine in all subsets of the pediatric population under 2 years of age (use in children and adolescents, see section 4.2).

5.2 Pharmacokinetic properties

Absorption
Bilastine is rapidly absorbed after oral administration, and the maximum plasma concentration is reached after approximately 1.3 hours. No accumulation of bilastine in the body has been observed. The mean bioavailability of bilastine after oral administration is 61%.
Distribution
In vitro and in vivo studies have shown that bilastine is a substrate for P-glycoprotein (see section 4.5 "Interactions with ketokonazole or erythromycin" and "Interactions with diltiazem") and organic anion-transporting polypeptides (OATP) (see section 4.5 "Interactions with grapefruit juice"). Bilastine is not a substrate for other transport proteins, such as BCRP or renal transporters OCT2, OAT1, and OAT3. Based on in vitro studies, it is not expected that bilastine will have an inhibitory effect on the following transport proteins in systemic circulation: P-gp, MRP2, BCRP, BSEP, OATP1B1, OATP1B3, OATP2B1, OAT1, OAT3, OCT1, OCT2, and NTCP, as only a mild inhibitory effect was shown in the case of P-glycoprotein, OATP2B1, and OCT1, with an estimated inhibitory concentration IC ≥300 µM, much higher than the calculated maximum plasma concentration of the drug (C) in plasma, so these interactions are not expected to be clinically significant. However, based on these results, it cannot be ruled out that bilastine may have an inhibitory effect on transport proteins present in the intestinal mucosa, such as P-glycoprotein.

• At therapeutic doses, bilastine binds to plasma proteins in 84-90%.

Metabolism
In vitro studies have shown that bilastine does not induce or inhibit the activity of CYP450 enzyme isoforms.
Elimination
In a mass balance study conducted in healthy adult volunteers, after administration of a single dose of 20 mg of radiolabeled bilastine, almost 95% of the administered dose was excreted in urine (28.3%) and feces (66.5%) in unchanged form, confirming that bilastine is not significantly metabolized in the human body. The mean elimination half-life of the product in healthy volunteers was 14.5 hours.
Linearity
Bilastine exhibits linear pharmacokinetics within the range of studied doses (5 to 220 mg) with minimal interindividual variability.
Renal impairment
In a study involving patients with renal impairment, the mean standard deviation of the area under the concentration-time curve (AUC) increased from 737.4 (±260.8) ng x h/ml in patients without renal impairment (GFR: >80 ml/min/1.73 m) to: 967.4 (±140.2) ng x h/ml in patients with mild renal impairment (GFR: 50-80 ml/min/1.73 m), 1384.2 (±263.23) ng x h/ml in patients with moderate renal impairment (GFR: 30-<50 ml min 1.73 m), and 1708.5 (±699.0) ng x h in patients with severe renal impairment (gfr: <30 m).
The mean standard deviation of the elimination half-life of bilastine was 9.3 hours (±2.8) in patients without renal impairment, 15.1 hours (±7.7) in patients with mild renal impairment, 10.5 hours (±2.3) in patients with moderate renal impairment, and 18.4 hours (±11.4) in patients with severe renal impairment. Bilastine was completely eliminated from the urine in all patients within 48-72 hours. The above pharmacokinetic changes do not have a significant impact on the safety of bilastine, as bilastine plasma concentrations in patients with renal impairment are within the safe range.
Hepatic impairment
There are no pharmacokinetic data in patients with hepatic impairment. Bilastine is not metabolized in the human body. Since studies in patients with renal impairment have shown that bilastine is mainly excreted by the kidneys, biliary excretion is only a minor part of the elimination process. Changes in liver function do not appear to significantly affect the pharmacokinetics of bilastine.
Elderly patients
There are limited data on the pharmacokinetics in patients over 65 years of age. No statistically significant differences in pharmacokinetics were observed in elderly patients compared to patients aged 18-35 years.
Children and adolescents
Due to the lack of available pharmacokinetic data in adolescents (12-17 years old), it was considered appropriate to extrapolate data from adults to adolescents for this product.
Pharmacokinetic data in children were obtained in a phase II pharmacokinetic study in which 31 children aged 4-11 years with allergic rhinitis and conjunctivitis or chronic urticaria received bilastine at a dose of 10 mg once daily in the form of orally disintegrating tablets.
A pharmacokinetic analysis showing the distribution of plasma concentrations indicated that in the case of bilastine at a dose of 10 mg intended for children, administered once daily, the systemic exposure is equivalent to that observed after a dose of 20 mg in adults and adolescents, and the mean AUC value is 1014 ng x h/ml in children aged 6-11 years. These results were well below the safety threshold established based on data on the administration of 80 mg once daily to adults, in accordance with the product's safety profile. The results of the study confirmed that a dose of 10 mg of bilastine administered orally once daily is a suitable therapeutic dose for children aged 6-11 years with a body weight of at least 20 kg.

5.3 Preclinical safety data

Non-clinical data on bilastine from conventional pharmacological safety studies, repeated dose toxicity studies, genotoxicity studies, and carcinogenic potential studies do not indicate any special hazard for humans.
In reproductive toxicity studies, the effect of bilastine on the fetus (pre- and post-implantation loss in rats and incomplete ossification of skull, sternum, and limbs in rabbits) was observed only at toxic doses in mothers. The no-observed-adverse-effect levels (NOAELs) are sufficiently higher (more than 30 times) than the exposure at the recommended therapeutic dose in humans.
In a lactation study, bilastine was detected in the milk of lactating female rats that received a single oral dose (20 mg/kg body weight). The concentrations of bilastine in milk were half of those in the maternal plasma. The significance of these findings for humans is unknown.
In a fertility study in rats, bilastine administered orally at doses up to 1000 mg/kg body weight per day did not affect female or male reproductive organs. There were no changes in mating indices, fertility indices, or conception rates.
As observed in a distribution study conducted in rats with radiolabeling, bilastine does not accumulate in the central nervous system.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Mannitol
Microcrystalline cellulose
Sodium carboxymethyl cellulose (type A)
Magnesium aluminometasilicate
Magnesium stearate
Colloidal anhydrous silica

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

No special storage precautions for the medicinal product.

6.5 Nature and contents of container

PVC/PVDC/Aluminum or OPA/Aluminum/PVC/Aluminum blister packs packaged in a cardboard box containing 10, 20, 30, 50, or 100 tablets.
Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

RESPONSIBLE FOR BATCH RELEASE

Polpharma S.A.
Pelplińska 19
83-200 Starogard Gdański

8. MARKETING AUTHORISATION NUMBER

Authorisation number 26559

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

DATE OF REVISION OF THE TEXT

Date of first authorisation: 06.08.2021

10. DATE OF REVISION OF THE TEXT

CHARACTERISTICS OF THE MEDICINAL PRODUCT

• 11.04.2025