Clatexo

SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT

Clatexo, 20 mg, tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 20 mg of bilastine ( Bilastinum ).
For a complete list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet
Round, white or almost white, biconvex tablets with a diameter of approximately 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 (aged 12 years and above).

4.2 Dosage and method of administration

Dosage
Adults and adolescents (aged 12 years and above)
20 mg of bilastine (1 tablet) once daily to relieve symptoms of allergic rhinitis and conjunctivitis (seasonal and perennial) as well as urticaria.
The tablet should be taken one hour before or two hours after a meal or fruit juice consumption (see section 4.5).

Duration of treatment
In cases of allergic rhinitis and conjunctivitis, treatment duration should be limited to the period of allergen exposure. In seasonal allergic rhinitis, treatment may be discontinued after symptoms resolve and resumed upon their recurrence.
For perennial allergic rhinitis, continuous treatment may be considered during periods of allergen exposure. The duration of treatment for urticaria depends on the type, duration, and course of the condition.

Special populations
Elderly patients
No dosage adjustment is necessary in elderly patients (see sections 5.1 and 5.2).

Renal impairment
Studies conducted in adult patients at particular risk (including those with renal impairment) indicate that dosage adjustment of Clatexo is not required in adult patients with impaired renal function (see section 5.2).

Hepatic impairment
Clinical studies in patients with hepatic impairment have not been performed. However, since bilastine is not metabolized and is excreted unchanged in urine and feces, hepatic impairment is not considered to increase systemic exposure beyond the safety margin in adult patients. Therefore, dosage adjustment is not required in patients with hepatic impairment (see section 5.2).

Children and adolescents

• Children aged 6 to 11 years weighing at least 20 kg: In this population, the following formulations are appropriate: bilastine 10 mg orodispersible tablets and bilastine oral solution 2.5 mg/ml.
• Children below 6 years of age or weighing less than 20 kg: Current data are presented in sections 4.4, 4.8, 5.1, and 5.2, but no dosage recommendations are available. Therefore, bilastine should not be used in this age group.

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

Method of administration
Oral use.
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.

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). Drugs that cause QT/QTc interval prolongation are suspected to increase the risk of ventricular tachycardia of the Torsade de pointes type.
Therefore, caution should be exercised when administering bilastine to patients who are at increased risk of QT/QTc interval prolongation. This includes patients with a history of cardiac arrhythmias, patients with hypokalaemia, hypomagnesaemia, or hypocalcaemia, patients with known QT interval prolongation or significant bradycardia, and patients receiving concomitant medicinal products that cause QT/QTc interval prolongation.
Children and adolescents
The efficacy and safety of bilastine in children under 2 years of age have not been established, and clinical data in children aged 2 to 5 years are limited; therefore, bilastine should not be used in these age groups.
In patients with moderate or severe renal impairment, co-administration of bilastine with P-glycoprotein (P-gp) inhibitors such as ketoconazole, erythromycin, cyclosporine, ritonavir or diltiazem may increase plasma concentrations of bilastine and thereby increase the risk of bilastine-related adverse reactions. Therefore, in patients with moderate or severe renal impairment, concomitant administration of bilastine with P-gp inhibitors should be avoided.
Clatexo contains sodium
The product contains less than 1 mmol of sodium (23 mg) per tablet; therefore, the product is considered "sodium-free".

4.5 Interactions with other medicinal products and other forms of interactions

Interaction studies have been conducted exclusively in adults, and their results are presented below.

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

Interactions with grapefruit juice: Concomitant administration of 20 mg bilastine and grapefruit juice reduces the bioavailability of bilastine by 30%. This effect may also apply to other fruit juices. The extent of reduced bioavailability may vary depending on the manufacturer and fruit type.

The mechanism of this interaction involves inhibition of the OATP1A2 polypeptide, 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 and rifampicin, may similarly reduce plasma concentrations of bilastine.

Interactions with ketoconazole or erythromycin: Concomitant administration of 20 mg bilastine once daily and 400 mg ketoconazole once daily or 500 mg erythromycin three times daily doubles the systemic exposure (AUC) and increases the maximum plasma concentration (C_max) of bilastine two- to threefold. These changes can be explained by 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 when co-administered with ketoconazole or erythromycin. Other medicinal products that are substrates or inhibitors of P-glycoprotein, such as cyclosporine, may increase plasma concentrations of bilastine.

Interactions with diltiazem: Concomitant administration of 20 mg bilastine once daily and 60 mg diltiazem once daily increases the maximum plasma concentration (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.

Interactions with alcohol: Psychomotor performance after concomitant intake of alcohol and 20 mg bilastine once daily was similar to that observed after alcohol and placebo administration.

Interactions with lorazepam: Concomitant administration of 20 mg bilastine once daily and 3 mg lorazepam once daily for 8 days did not enhance the central nervous system depressant effect of lorazepam.

Children and adolescents
Interaction studies have been conducted exclusively in adults. Due to lack of clinical experience in children regarding interactions between bilastine and other medicinal products, food, and fruit juices, the results of interaction studies in adults should be taken into account when prescribing bilastine to children. There are no clinical data in children to determine whether changes in AUC or C_max due to interactions affect the safety profile of bilastine.

4.6 Fertility, pregnancy and lactation

Pregnancy
There are no data or data are limited regarding the use of bilastine in pregnant women.
Studies conducted in animals have not shown any direct or indirect harmful effects related to reproductive toxicity, course of delivery, or neonatal development (see section 5.3). As a precautionary measure, it is recommended to avoid the use of bilastine during pregnancy.

Breastfeeding
Excretion of bilastine into human milk has not been studied. Based on available pharmacokinetic data from animal studies, bilastine is excreted into milk (see section 5.3). A decision on whether to continue or discontinue breastfeeding or to discontinue bilastine therapy should be made taking into account the benefits of breastfeeding for the child and the benefits of bilastine treatment for the mother.

Fertility
Clinical data are lacking or limited in quantity. 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 driving ability showed that administration of bilastine at a dose of 20 mg did not impair driving performance. However, individual response to treatment may vary; therefore, patients should be advised not to drive or operate machinery until they have determined how they react 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 bilastine 20 mg in clinical trials was comparable to that in patients receiving placebo (12.7% vs. 12.8%).
Phase II and III clinical trials conducted during clinical development included 2525 adult and adolescent patients treated with bilastine at various doses, of whom 1697 received bilastine 20 mg. In these trials, 1362 patients received placebo. The most commonly reported adverse reactions in patients receiving 20 mg bilastine for allergic rhinitis and conjunctivitis or chronic idiopathic urticaria were: headache, somnolence, dizziness, and fatigue. These same adverse reactions occurred with comparable frequency in patients receiving placebo.

Tabulated summary of adverse reactions in adult and adolescent patients
Adverse reactions at least probably related to bilastine and reported in more than 0.1% of patients receiving 20 mg bilastine during clinical development (N=1697) are listed below.
Frequencies are classified 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 (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
System organ class
Bilastine 20 mg Placebo
Adverse reaction N=1697 Regardless of dose N=1362
Frequency
N=2525
Infections and infestations
Uncommon Oral herpes 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 14 (0.83%) 23 (0.91%) 8 (0.59%)
central origin

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

Cardiac disorders
Uncommon Right bundle 4 (0.24%) 5 (0.20%) 3 (0.22%)
branch block
Sinus arrhythmia 5 (0.30%) 5 (0.20%) 1 (0.07%)
Prolongation of 9 (0.53%) 10 (0.40%) 5 (0.37%)
QT interval in
electrocardiogram*

*Cases of QT interval prolongation in the electrocardiogram have also been reported after marketing authorization.
Frequency unknown (cannot be estimated from available data):
palpitations, tachycardia, hypersensitivity reactions (e.g. anaphylactic reaction, angioedema, dyspnea, rash, local swelling and erythema), and vomiting have been observed in the post-marketing period.

Description of selected adverse reactions in adult and adolescent patients
In patients receiving bilastine 20 mg or placebo, somnolence, headache, dizziness, and fatigue were reported. The frequency of occurrence for bilastine and placebo 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, respectively.

Data collected during post-marketing surveillance confirmed the safety profile observed during clinical development.

Summary of safety profile in children and adolescents
During clinical development, the frequency, type, and severity of adverse reactions in adolescents aged 12–17 years were consistent with those observed in adults. Data collected in this population (adolescents) during post-marketing surveillance confirmed the results of clinical trials.

The proportion of children (aged 2 to 11 years) treated for allergic rhinoconjunctivitis or chronic idiopathic urticaria who reported adverse reactions after receiving bilastine 10 mg in a 12-week controlled clinical study was comparable to the proportion in the placebo group (68.5% vs. 67.5%).

The most commonly reported adverse reactions in 291 children (aged 2–11 years) receiving bilastine (in the form of orally disintegrating tablets) in a clinical trial (#260 children participating in a safety study, 31 children participating in a pharmacokinetic study) included headache, allergic conjunctivitis, rhinitis, and abdominal pain. These same adverse reactions occurred with similar frequency in 249 patients receiving placebo.

Tabulated summary of adverse reactions in the pediatric and adolescent population
Adverse reactions considered at least possibly related to bilastine administration, reported in more than 0.1% of children (aged 2–11 years) receiving bilastine during clinical development, are presented in the table below.

Frequency categories are defined 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 (frequency cannot be estimated from available data)

Adverse reactions occurring rarely, very rarely, or with unknown frequency are not included in the table.

System Organ Class Bilastine 10 mg Placebo (n=249)
Frequency Adverse Reaction (n=291)

Infections and infestations
Common Rhinitis 3 (1.0%) 3 (1.2%)

Nervous system disorders
Common Headache 6 (2.1%) 3 (1.2%)
Uncommon Central origin dizziness 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, epigastric pain 3 (1.0%) 3 (1.2%)
Uncommon Diarrhea 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 the pediatric and adolescent population
In children receiving bilastine 10 mg or placebo, headache, abdominal pain, allergic conjunctivitis, and rhinitis were reported. The frequency of occurrence for bilastine and placebo 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, respectively.

Reporting suspected adverse reactions
After marketing authorization of a medicinal product, it is important to report suspected adverse reactions. This enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Suspected adverse reactions can also be reported to the responsible entity.

4.9 Overdose

Information regarding acute overdose of bilastine comes from experience in clinical trials conducted during drug development and post-marketing surveillance. In clinical trials, administration of bilastine at doses 10 to 11 times higher than the therapeutic dose (220 mg as a single dose or 200 mg daily for 7 days) to 26 healthy adult volunteers resulted in a twofold increase in the frequency of adverse reactions compared to placebo. The most commonly reported adverse reactions were dizziness, headache, and nausea. No severe adverse reactions or clinically significant QTc interval prolongation were observed. Post-marketing surveillance data are consistent with findings from clinical trials.

A thorough assessment of the effect of multiple doses of bilastine (100 mg x 4 days) on ventricular repolarization during a "crossover thorough QT/QTc study" involving 30 healthy adult volunteers did not reveal any clinically significant QTc interval prolongation.

There is no data available on overdose in children.

In case of overdose, symptomatic and supportive treatment is recommended.

There is no known specific antidote for bilastine.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: antihistamines for systemic use, other antihistamines for systemic use, ATC code R06AX29.

Mechanism of action

Bilastine has no sedative properties. It is a long-acting histamine antagonist with selective affinity for peripheral H₁ receptors and no affinity for muscarinic receptors.

Bilastine inhibits histamine-induced wheal and flare reactions for up to 24 hours after a single dose.

Clinical efficacy and safety

In clinical trials conducted in adult and adolescent patients with allergic rhinoconjunctivitis (seasonal and perennial), bilastine 20 mg administered once daily for 14–28 days effectively relieved symptoms such as sneezing, rhinorrhea, nasal itching, nasal congestion, ocular itching, tearing, and eye redness.

Bilastine provided effective symptom control over 24 hours.

In two clinical trials involving patients with chronic idiopathic urticaria, bilastine 20 mg once daily for 28 days effectively reduced symptoms including intensity of itching, number and size of wheals, and patient discomfort due to urticaria. In these patients, improvements in sleep quality and quality of life were observed.

In clinical trials, bilastine did not cause any clinically significant QTc interval prolongation or other cardiovascular effects, even when administered at a dose of 200 mg daily (10 times the clinical dose) for 7 days in 9 patients, or when co-administered with P-glycoprotein inhibitors such as ketoconazole (24 patients) and erythromycin (24 patients). Additionally, a dedicated QT interval study was conducted in 30 volunteers.

In controlled clinical trials at the recommended dose of 20 mg once daily, the central nervous system safety profile of bilastine was similar to placebo, and the incidence of somnolence did not differ statistically from placebo. Bilastine at doses up to 40 mg once daily did not impair psychomotor performance in clinical studies or ability to drive during a standard driving test.

Phase II and III clinical trials did not show differences in efficacy and safety of bilastine between elderly patients (≥65 years) and younger patients. A post-marketing study involving 146 elderly patients did not reveal any differences in safety profile compared to adult patients.

Children and adolescents

Adolescents (aged 12 to 17 years) were included in clinical trials. During clinical trials, 128 adolescents received bilastine (81 adolescents in a double-blind trial for allergic rhinoconjunctivitis), and an additional 116 adolescents were randomized to receive comparator drug or placebo. No differences in efficacy and safety were observed between adults and adolescents.

According to guidelines, demonstrated efficacy in adults and adolescents may be extrapolated to children, provided that systemic exposure to bilastine at a dose of 10 mg in children aged 6 to 11 years weighing at least 20 kg is shown to be equivalent to exposure at a dose of 20 mg in adults (see section 5.2). Extrapolation from adult and adolescent data is considered appropriate for this medicinal product, as the pathophysiology of allergic rhinoconjunctivitis and urticaria is the same across all age groups.

In a 12-week controlled clinical trial involving children aged 2–11 years (total of 509 children: 260 treated with bilastine 10 mg: 58 aged 2 to <6 years, 105 aged 6 to <9 years, and 97 aged 9 to <12 years; and 249 treated with placebo: 58 aged 2 to <6 years, 95 aged 6 to <9 years, and 96 aged 9 to <12 years), bilastine was administered at the recommended pediatric dose of 10 mg once daily. The safety profile of bilastine (n=260) was similar to placebo (n=249). Adverse reactions were reported in 5.8% of patients receiving bilastine 10 mg and 8.0% of those receiving placebo. Both bilastine 10 mg and placebo groups showed a slight decrease in sleepiness and sedation scores according to the Paediatric Sleep Questionnaire, with no statistically significant differences between treatment groups. In these children aged 2 to 11 years, no clinically significant differences in QTc interval were observed after administration of 10 mg bilastine compared to placebo. A quality-of-life questionnaire for children with allergic conjunctivitis and rhinitis or chronic urticaria showed overall improvement (in score points) after 12 weeks, with no statistically significant differences between bilastine and placebo arms.

A total of 509 children were included in the study: 479 with allergic rhinoconjunctivitis and 30 with chronic urticaria. Of the 260 children receiving bilastine, 252 (96.9%) had allergic rhinoconjunctivitis and 8 (3.1%) had chronic urticaria. Similarly, of the 249 children receiving placebo, 227 (91.2%) had allergic rhinoconjunctivitis and 22 (8.8%) had chronic urticaria.

The European Medicines Agency has waived the requirement to submit results of bilastine studies in all pediatric subpopulations 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, reaching maximum plasma concentration at approximately 1.3 hours. No accumulation of bilastine in the body has been observed. The mean bioavailability of bilastine following oral dosing is 61%.

Distribution
In vitro and in vivo studies have shown that bilastine is a substrate of P-glycoprotein (see section 4.5 "Interactions with ketoconazole or erythromycin" and "Interactions with diltiazem") and organic anion transporting polypeptides (OATP). Bilastine is not a substrate for other transporter proteins such as BCRP or renal transporters OCT2, OAT1, and OAT3. Based on in vitro studies, inhibitory effects of bilastine on the following systemic transporters are not expected: P-gp, MRP2, BCRP, BSEP, OATP1B1, OATP1B3, OATP2B1, OAT1, OAT3, OCT1, OCT2, and NTCP, since only a mild inhibitory effect was observed for P-glycoprotein, OATP2B1, and OCT1, with an estimated inhibitory concentration IC ≥300 µM, significantly higher than the calculated maximum plasma concentration (C) of the drug; therefore, these interactions are not clinically relevant. However, based on these results, an inhibitory effect of bilastine on transporter proteins present in the intestinal mucosa, such as P-glycoprotein, cannot be ruled out.

At therapeutic doses, bilastine is plasma protein-bound by 84–90%.

Metabolism
In vitro studies indicate that bilastine does not induce or inhibit the activity of CYP450 isoenzymes.

Elimination
In a mass balance study conducted in healthy adult volunteers following a single 20 mg dose of carbon-14 labeled bilastine, nearly 95% of the administered dose was excreted unchanged in urine (28.3%) and feces (66.5%), confirming that bilastine is not significantly metabolized in humans. The mean elimination half-life in healthy volunteers was 14.5 hours.

Linearity
Bilastine exhibits linear pharmacokinetics over the dose range studied (5 to 220 mg) with low inter-individual 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·h/mL in patients with normal renal function (GFR: >80 mL/min/1.73 m²) to 967.4 (±140.2) ng·h/mL in patients with mild renal impairment (GFR: 50–80 mL/min/1.73 m²), 1384.2 (±263.23) ng·h/mL in patients with moderate renal impairment (GFR: 30 to <50 mL/min/1.73 m²), and 1708.5 (±699.0) ng·h/mL in patients with severe renal impairment (GFR: <30 mL/min/1.73 m²).

The mean standard deviation of bilastine half-life was 9.3 hours (±2.8) in patients with normal renal function, 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 excreted in urine within 48–72 hours in all patients. These pharmacokinetic changes do not have a significant impact on the safety of bilastine, as plasma concentrations of bilastine in patients with renal impairment remain within a safe range.

Hepatic impairment
There are no pharmacokinetic data available in individuals with hepatic impairment. Bilastine is not metabolized in the human body. Since studies in patients with renal impairment have shown that bilastine is primarily eliminated via the kidneys, with biliary excretion accounting for only a minor portion of total elimination, changes in liver function are not expected to significantly affect the pharmacokinetics of bilastine.

Elderly patients
Limited pharmacokinetic data are available for individuals aged over 65 years. No statistically significant differences in pharmacokinetics have been observed in elderly subjects compared to those aged 18 to 35 years.

Children and adolescents
Due to the lack of available pharmacokinetic data in adolescents (aged 12 to 17 years), extrapolation of adult data to adolescents was considered appropriate for this product.

Pharmacokinetic data in children were obtained from a Phase II pharmacokinetic study involving 31 children aged 4 to 11 years with allergic rhinoconjunctivitis or chronic urticaria, who received 10 mg of bilastine once daily in the form of orally disintegrating tablets.

Pharmacokinetic analysis of plasma concentration profiles demonstrated that systemic exposure following a 10 mg once-daily dose of bilastine in children is equivalent to that observed after a 20 mg dose in adults and adolescents, with a mean AUC of 1014 ng·h/mL in children aged 6 to 11 years. These values were well below the safety threshold established based on data from administration of 80 mg once daily to adults, according to the product's safety profile. Study results confirmed that a 10 mg once-daily oral dose of bilastine is an appropriate therapeutic dose for children aged 6 to 11 years weighing at least 20 kg.

5.3 Preclinical safety data

Non-clinical data on bilastine derived from conventional pharmacological safety studies, repeated-dose toxicity, genotoxicity, and potential carcinogenicity revealed no special hazard for humans.
In reproductive toxicity studies, effects on the fetus (pre- and postimplantation loss in rats, and incomplete ossification of skull, sternebrae, and limb bones in rabbits) were observed only when toxic maternal doses were administered. The no-observed-adverse-effect levels (NOAELs) were sufficiently higher (over 30 times) than exposure at the recommended therapeutic dose in humans.
In a lactation study, bilastine was detected in the milk of nursing rat females following a single oral dose (20 mg/kg body weight). Bilastine concentrations in milk were half those in 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 had no effect on male or female reproductive organs. Mating, fertility, and pregnancy rates were unaffected.
As observed in a distribution study conducted in rats using quantitative autoradiography to determine drug concentrations, bilastine does not accumulate in the central nervous system.
6. PHARMACEUTICAL DATA
6.1 List of excipients
Mannitol
Microcrystalline cellulose
Sodium carboxymethyl starch (type A)
Magnesium aluminum metasilicate
Magnesium stearate
Colloidal anhydrous silica

6.2 Pharmaceutical incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

No special requirements for storage of the medicinal product.

6.5 Type and contents of container

PVC/PVDC/Aluminium or OPA/Aluminium/PVC/Aluminium blisters packed in cardboard boxes containing 10, 20, 30, 50 or 100 tablets.
Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused residues of the medicinal product or its waste must be disposed of in accordance
with local regulations.

7. MARKETING AUTHORISATION HOLDER

FOR SALE
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19
83-200 Starogard Gdański

8. MARKETING AUTHORISATION NUMBER

Authorisation number: 26559

9. DATE OF FIRST AUTHORISATION

AND DATE OF RENEWAL
Date of first authorisation: 06.08.2021.

10. DATE OF ADOPTION OR PARTIAL CHANGE OF THE TEXT

SUMMARY OF PRODUCT CHARACTERISTICS
11.04.2025