Alerik neo

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ALEK® Neo (ALERIC® Neo)

Composition:

Active substance: desloratadine;

1 ml of solution contains 0.5 mg of desloratadine;

Excipients: hypromellose; sucralose; citric acid; sodium citrate; sorbitol solution, non-crystallizing; propylene glycol; Tuttie-Frutti flavoring; purified water.

Pharmaceutical form. Oral solution.

Main physicochemical properties: clear, transparent solution with a pleasant fruity odor.

Pharmacotherapeutic group. Systemic antihistamines.

ATC code R06A X27.

Pharmacological Properties

Pharmacodynamics.

Mechanism of action.

Desloratadine is a non-sedating, long-acting histamine antagonist that exerts a selective antagonistic effect on peripheral H1-receptors. After oral administration, desloratadine selectively blocks peripheral H1-histamine receptors, as the substance barely penetrates the central nervous system (CNS).

In in vitro studies, desloratadine demonstrated anti-allergic properties, including inhibition of pro-inflammatory cytokine release (such as IL-4, IL-6, IL-8, and IL-13) from human mast cells/basophils, as well as suppression of adhesion molecule expression, such as P-selectin on endothelial cells. The clinical significance of these observations remains to be confirmed.

Clinical efficacy and safety.

Children. The efficacy of desloratadine oral solution has not been studied in specific pediatric trials. However, the safety of use in children has been evaluated in three clinical studies with desloratadine syrup containing a similar concentration of active substance as the oral solution. Children aged 1–11 years requiring antihistamine therapy received desloratadine at a daily dose of 1.25 mg (for ages 1–5 years) or 2.5 mg (for ages 6–11 years). The treatment was well tolerated, as confirmed by clinical and laboratory test results, vital function status, and ECG data, including QTc interval duration. When used at recommended doses, plasma desloratadine concentrations were comparable between adult and pediatric populations. Therefore, since the course of allergic rhinitis and chronic idiopathic urticaria, as well as the pharmacological profile of desloratadine, are similar in children and adults, efficacy data from adult studies may be extrapolated to the pediatric population.

The efficacy of desloratadine syrup has not been investigated in pediatric studies involving children under 12 years of age.

Adults and adolescents. In a multiple-dose clinical study in adults and adolescents, in which desloratadine was administered daily at doses up to 20 mg for 14 days, no statistically or clinically significant cardiovascular effects were observed. In a clinical pharmacology study, administration of desloratadine to adults and adolescents at a dose of 45 mg per day (9 times higher than the clinical dose) for 10 days did not result in QTc interval prolongation.

Pharmacodynamic effects.

Desloratadine barely penetrates the nervous system. In controlled clinical trials, the incidence of somnolence with the recommended daily dose of 5 mg in adults and adolescents did not differ from the placebo group. In clinical studies, a single 7.5 mg dose of desloratadine tablets did not affect psychomotor performance. In a single-dose study in adults, desloratadine 5 mg did not affect standard flight performance parameters, including subjective drowsiness or flight-related tasks.

In clinical pharmacological studies involving adults, concomitant use with alcohol did not increase alcohol-induced impairment of performance or increased somnolence. No significant differences were observed in psychomotor test results between desloratadine and placebo groups, regardless of whether they were taken alone or with alcohol.

No clinically significant changes in plasma desloratadine concentrations were observed with repeated administration of ketoconazole and erythromycin.

In adults and adolescents with allergic rhinitis, desloratadine tablets effectively relieved and controlled symptoms such as sneezing, itching and nasal discharge, eye itching and redness, lacrimation, and palate itching for up to 24 hours. The efficacy of desloratadine tablets in adolescents aged 12–17 years has not been definitively demonstrated in clinical trials.

In addition to the conventional classification of allergic rhinitis into seasonal and perennial forms, allergic rhinitis may alternatively be classified by symptom duration as intermittent or persistent. Intermittent allergic rhinitis is defined as symptoms occurring for less than 4 days per week or less than 4 weeks. Persistent allergic rhinitis is characterized by symptoms occurring for 4 or more days per week or for more than 4 weeks.

Desloratadine tablets effectively reduce the severity of seasonal allergic rhinitis, as evidenced by the total score of the rhinoconjunctivitis quality-of-life questionnaire. The greatest improvement was observed in questionnaire items related to practical problems and daily activities limited by symptoms.

Chronic idiopathic urticaria has been studied as a clinical model of urticarial disorders because the underlying mechanisms are similar regardless of etiology. Histamine release is a causative factor in all urticarial disorders; therefore, desloratadine may effectively relieve symptoms of all urticarial disorders, including chronic idiopathic urticaria.

In two 6-week, placebo-controlled studies involving patients with chronic idiopathic urticaria, desloratadine effectively reduced itching and decreased the number and size of skin lesions by the end of the first dosing interval. In each study, the effect lasted throughout the 24-hour dosing interval. As in other clinical trials of antihistamines in chronic idiopathic urticaria, a small number of patients considered non-responsive to antihistamines were excluded from the study. Itching relief of more than 50% was observed in 55% of patients receiving desloratadine compared to 19% of patients receiving placebo. Desloratadine treatment also significantly reduced the impact of the disease on sleep and daytime activity, as measured by a four-point scale used to assess these changes.

Pharmacokinetics.

Absorption.

Plasma concentrations of desloratadine are detectable within 30 minutes after administration. Desloratadine is well absorbed, with maximum plasma concentration (Cmax) reached approximately 3 hours post-dose. The elimination half-life is approximately 27 hours. The extent of desloratadine accumulation corresponds to its half-life (approximately 27 hours) and the once-daily dosing frequency.

In a series of clinical and pharmacokinetic studies, 6% of subjects exhibited higher desloratadine concentrations. The prevalence of the poor metabolizer phenotype was comparable in adults (6%) and children aged 2–11 years (6%), and higher among individuals of other ethnic groups (African descent: 18% of adults and 16% of children; Caucasian descent: 2% of adults and 3% of children, respectively).

In a multiple-dose pharmacokinetic study using desloratadine tablets in healthy adult volunteers, 4 subjects were identified as poor metabolizers. Their Cmax, measured approximately 7 hours post-dose, was on average 3 times higher, and the terminal elimination half-life was approximately 89 hours.

In a multiple-dose pharmacokinetic study using desloratadine syrup in children aged 2–11 years with allergic rhinitis who were poor metabolizers, the area under the plasma concentration-time curve (AUC) of desloratadine was approximately 6 times higher, Cmax was approximately 3–4 times higher at 3–6 hours, and the terminal elimination half-life was approximately 120 hours. AUC was similar in adults and children with poor metabolism when age-appropriate doses were administered. The safety profile in these patients did not differ from that in the general population. The effects of desloratadine in poor metabolizers under 2 years of age have not been studied.

In separate single-dose studies in pediatric patients receiving recommended doses, AUC and Cmax values of desloratadine were comparable to those in adults receiving 5 mg desloratadine syrup.

Distribution.

Desloratadine is moderately bound to plasma proteins (83–87%). No evidence of clinically significant drug accumulation was observed after administration of desloratadine doses (5–20 mg) once daily for 14 days.

Bioequivalence between desloratadine tablets and syrup containing the same active substance concentration has been demonstrated. Since the oral solution and syrup contain the same concentration of active substance, the oral solution is expected to be bioequivalent to both the syrup and tablets.

Biotransformation.

The enzyme responsible for desloratadine metabolism has not yet been identified; therefore, some drug interactions cannot be entirely excluded. Desloratadine does not inhibit CYP3A4 in vivo. In vitro studies have shown that the drug does not inhibit CYP2D6 and is neither a substrate nor an inhibitor of P-glycoprotein.

Elimination.

In a single-dose study of 7.5 mg desloratadine, food intake (a high-fat, high-calorie meal) did not affect the pharmacokinetics of desloratadine. Grapefruit juice has also been shown not to affect desloratadine pharmacokinetics.

Patients with renal impairment.

The pharmacokinetics of desloratadine in patients with chronic kidney disease (CKD) was compared to that in healthy volunteers in one single-dose and one multiple-dose study. In the single-dose study, the AUC of desloratadine was approximately 2 and 2.5 times higher in patients with mild, moderate, and severe CKD, respectively, compared to healthy volunteers. In the multiple-dose study, steady state was achieved by day 11, and compared to healthy volunteers, the AUC of desloratadine was approximately 1.5 times higher in patients with mild and moderate CKD and approximately 2.5 times higher in patients with severe CKD. In both studies, changes in exposure (AUC and Cmax) of desloratadine and 3-hydroxydesloratadine were not clinically significant.

Clinical characteristics.

Indications.

The medicinal product Aleric Neo is indicated for use in adults, adolescents, and children from 1 year of age for the relief of symptoms associated with:

• allergic rhinitis;
• urticaria.

Contraindications.

Hypersensitivity to desloratadine or to any excipient of the product, or to loratadine.

Interaction with other medicinal products and other forms of interaction.

In clinical studies, no clinically significant interactions were observed when desloratadine tablets were administered concomitantly with erythromycin or ketoconazole.

Children. Interaction studies have been conducted only in adults.

In clinical pharmacological studies, no enhanced negative effect of ethanol was observed when desloratadine tablets were administered together with alcohol. However, during the post-marketing period, cases of alcohol intolerance and alcohol intoxication have been reported during treatment with the medicinal product. Therefore, caution should be exercised when consuming alcohol during desloratadine therapy.

Special precautions for use.

Alerik Neo should be used with caution in patients with severe renal impairment.

Desloratadine should be used with caution in patients with a history of seizures, either personal or familial. Children may be more susceptible to developing new seizures during desloratadine treatment. The physician should consider discontinuing desloratadine treatment in patients who experience a seizure while taking the medication.

Since allergic rhinitis is difficult to differentiate from other forms of rhinitis in children under 2 years of age, medical history, physical examination findings, skin and laboratory tests should be taken into account, along with the absence of upper respiratory tract infection or structural abnormalities.

Approximately 6% of adults and children aged 2–11 years have a slow metabolism of desloratadine, resulting in increased drug exposure. The safety profile of desloratadine in children aged 2–11 years is similar between slow and normal metabolizers. The effects of desloratadine in children under 2 years of age who are slow metabolizers have not been studied.

The medication contains sorbitol and therefore should not be used in patients with hereditary fructose intolerance.

Use during pregnancy or breastfeeding.

Extensive data on the use of desloratadine during pregnancy (over 1000 cases) indicate no teratogenic, fetotoxic effects or adverse effects on the newborn. Animal studies have not shown any direct or indirect adverse effects on reproductive function. As a precautionary measure, it is advisable to avoid using Alerik Neo during pregnancy.

Desloratadine has been detected in the bodies of newborns/infants breastfed by women taking this medication. The impact of desloratadine on newborns/infants is unknown. Breastfeeding women should decide whether to discontinue breastfeeding or avoid using the drug, taking into account the benefits of breastfeeding for the child and the therapeutic benefits of the drug for the mother.

Data on the effects of desloratadine on male or female fertility are lacking.

Ability to affect reaction speed when driving or operating machinery.

Clinical trial data indicate that desloratadine does not affect or has a negligible effect on the ability to drive or operate machinery. Patients should be informed that most people do not experience drowsiness. However, individual responses to medications may vary. Patients should avoid engaging in activities requiring mental alertness, such as driving a car or operating machinery, until they have determined how they react to the medication.

Dosage and Administration.

Adults and adolescents (aged 12 years and older): 10 mL of solution (5 mg of desloratadine) once daily.

Children.

It should be noted that most cases of rhinitis in children under 2 years of age are infectious, and there are no data confirming the treatment of infectious rhinitis with desloratadine.

The following dosing regimen should be used for treatment:

• children aged 1 to 5 years: 2.5 mL of solution (1.25 mg of desloratadine) once daily;
• children aged 6 to 11 years: 5 mL of solution (2.5 mg of desloratadine) once daily.

The safety and efficacy of oral desloratadine solution in children under 1 year of age have not been established.

There is limited clinical trial experience regarding the efficacy of desloratadine in children aged 1 to 11 years and adolescents aged 12 to 17 years.

Treatment of intermittent allergic rhinitis (symptoms present less than 4 days per week or less than 4 weeks) should be based on patient history: discontinue after symptoms resolve and restart if symptoms reappear.

For persistent allergic rhinitis (symptoms present more than 4 days per week or more than 4 weeks), treatment should continue throughout the entire period of allergen exposure.

The medicinal product Alerik Neo should be administered orally, independent of food intake.

Children.

The efficacy and safety of Alerik Neo in children under 1 year of age have not been established. For detailed information, see section "Dosage and Administration".

Overdose.

According to post-marketing data, the adverse reaction profile associated with overdose was similar to that of therapeutic doses, but the manifestations were more pronounced.

Treatment. In case of overdose, standard measures aimed at removing unabsorbed active substance should be taken; symptomatic and supportive therapy should be administered.

Desloratadine is not removed by hemodialysis; the possibility of its removal by peritoneal dialysis has not been established.

Symptoms. During clinical trials of repeated desloratadine administration at doses up to 45 mg (9 times the therapeutic dose), no clinically significant effects were observed.

Children. According to post-marketing experience, the adverse reaction profile associated with overdose is similar to that seen with therapeutic doses, although the manifestations may be more severe.

Adverse Reactions

During clinical trials evaluating the use of desloratadine for indications including allergic rhinitis and chronic idiopathic urticaria, adverse reactions were observed 3% more frequently in patients receiving a 5 mg daily dose compared to those receiving placebo. The most commonly reported adverse reactions, compared to placebo, were fatigue (1.2%), dry mouth (0.8%), and headache (0.6%). In trials involving children aged 2 to 11 years, the incidence of adverse reactions was similar in both the group receiving desloratadin syrup and the placebo group. In children aged 6 to 23 months, the most frequently reported adverse reactions (compared to placebo) were diarrhea (3.7%), fever (2.3%), and insomnia (2.3%).

There is a risk of psychomotor hyperactivity (abnormal behavior) associated with the use of desloratadine, which may manifest as irritability, aggression, and excitability.

In the post-marketing period, the following events have been observed (frequency unknown): QT interval prolongation, arrhythmia, and bradycardia.

Other adverse reactions reported very rarely during the post-marketing period are listed in Table 1. The frequency of adverse reactions is classified as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000), and frequency not known (cannot be estimated based on available data).

Table 1.

Desloratadine hardly penetrates into the CNS. When used at the recommended adult dose of 5 mg, no increase in the incidence of somnolence was observed compared with the placebo group. In studies of desloratadine at a single daily dose of 7.5 mg, no effect on psychomotor performance was detected.

Reporting of adverse reactions after drug registration is of great importance. It enables continuous monitoring of the benefit-risk balance of the drug. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of drug efficacy through the automated pharmacovigilance information system at https://aisf.dec.gov.ua.

Shelf life. 3 years.

After first opening of the bottle, the shelf life is 6 months.

Storage conditions.

No special storage temperature conditions required.

Store in the original packaging.

Keep out of the reach of children.

Packaging.

Bottles of 60 ml and 150 ml, closed with a screw cap with child-resistant closure, supplied with a measuring spoon or a dosing syringe, in a cardboard box.

Availability. Over-the-counter.

Manufacturer.

FAMAR A.V.E. AVLON PLANT 49th km NATIONAL ROAD ATHENS-LAMIA /
FAMAR A.V.E. AVLON PLANT 49th km NATIONAL ROAD ATHENS-LAMIA.

Manufacturer's address and location of operations.

49th km National Road Athens-Lamia, Avlona Attiki, 19011, Greece /
49th km National Road Athens-Lamia, Avlona Attiki, 19011, Greece.

Marketing authorization holder.

Unilab, LP / Unilab, LP.

Address of the marketing authorization holder.

966 Hungerford Drive, Suite 3B, Rockville, MD 20850, USA /
966 Hungerford Drive, Suite 3B, Rockville, MD 20850, USA.