Fexofen-sanovel

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FEXOFEN–sanovel (FEXOFEN–sanovel)

Composition:

Active substance: fexofenadine;

1 tablet contains 120 mg of fexofenadine hydrochloride;

Excipients: sodium croscarmellose, microcrystalline cellulose, pregelatinized starch, colloidal anhydrous silicon dioxide, povidone, magnesium stearate;

coating: Opadry II pink (lactose monohydrate; iron oxide red (E 172); polyethylene glycol 4000; hydroxypropylmethylcellulose; titanium dioxide (E 171)).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: elongated biconvex film-coated tablets of pink color.

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC code R06AX26.

Pharmacological properties.

Pharmacodynamics.

Fexofenadine is a specific H1-histamine receptor blocker. Fexofenadine is the pharmacologically active metabolite of terfenadine.

In clinical studies of histamine-induced skin wheal and flare reactions, the antihistaminic effect of fexofenadine hydrochloride administered once or twice daily was evident within 1 hour, reached maximum effect at 6 hours, and lasted for 24 hours. There was no evidence of tachyphylaxis even after 28 days of treatment. Clinical effect was observed after single oral doses ranging from 10 to 130 mg. In this model of antihistaminic efficacy, doses of at least 130 mg were required to maintain a consistent effect over 24 hours. The maximum inhibition of wheal and flare exceeded 80%. Clinical studies of seasonal allergic rhinitis indicate that a 120 mg dose is sufficient to provide 24-hour efficacy.

In patients with seasonal allergic rhinitis who received up to 240 mg of fexofenadine hydrochloride twice daily for 2 weeks, no changes in QT interval were observed compared to placebo.

Similarly, no such changes were observed compared to placebo in healthy volunteers who received up to 60 mg of fexofenadine hydrochloride twice daily for 6 months, 400 mg of fexofenadine hydrochloride twice daily for 6.5 days, or 240 mg daily for one year. In children aged 6 to 11 years, no statistically significant changes in QT interval were observed compared to placebo after administration of fexofenadine hydrochloride at a dose of 60 mg twice daily for 2 weeks.

Even at plasma concentrations 32 times higher than therapeutic levels, fexofenadine showed no effect on the delayed rectifier potassium channels cloned from human myocardium.

Pharmacokinetics.

Fexofenadine hydrochloride is rapidly absorbed after oral administration. Maximum concentration is reached approximately within 1–3 hours. Peak plasma concentration is approximately 289 ng/mL after a single 120 mg dose once daily and approximately 494 ng/mL after a single 180 mg dose once daily.

60–70% of fexofenadine is bound to plasma proteins.

Fexofenadine is not metabolized in the liver. It undergoes minimal metabolism, as the parent drug is primarily excreted unchanged in urine and feces. Elimination of fexofenadine from plasma occurs in a biphasic manner, with a terminal elimination half-life of 11 to 15 hours after repeated dosing. The kinetics of single and multiple doses are linear at oral doses up to 120 mg twice daily.

According to available study data, the majority of the dose is excreted in bile, while up to 10% is excreted unchanged in urine.

Clinical characteristics.

Indications.

Symptomatic treatment of seasonal allergic rhinitis in adults and children aged 12 years and older.|urticaria| e

Contraindications.

Hypersensitivity to any component of the drug.

Children under 12 years of age, due to lack of adequate safety and efficacy data.

Interaction with other medicinal products and other forms of interaction.

Fexofenadine is not metabolized in the liver, therefore it does not interact with other medicinal products via this mechanism.

Fexofenadine is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP). Concomitant use of fexofenadine with inhibitors or inducers of P-gp may affect fexofenadine exposure. It has been established that concomitant administration of fexofenadine hydrochloride with P-gp inhibitors erythromycin or ketoconazole leads to a 2- to 3-fold increase in plasma levels of fexofenadine. These changes were not associated with any effect on the QT interval and were not linked to any increased incidence of adverse reactions compared to drugs administered separately.

A clinical drug interaction study showed that concomitant use of apalutamide (a weak P-gp inducer) and a single oral dose of 30 mg fexofenadine resulted in a 30% reduction in fexofenadine AUC.

No interaction between fexofenadine and omeprazole was observed. However, administration of an antacid containing aluminium and magnesium hydroxide 15 minutes prior to fexofenadine hydrochloride caused reduced bioavailability, most likely due to binding in the gastrointestinal tract. A 2-hour interval is recommended between administration of fexofenadine hydrochloride and antacids containing aluminium and magnesium hydroxide.

Administration of antacids containing aluminium or magnesium hydroxides 15 minutes prior to taking 120 mg fexofenadine hydrochloride tablets reduces the bioavailability of fexofenadine hydrochloride due to binding in the gastrointestinal tract. A 2-hour interval should be maintained between administration of fexofenadine hydrochloride and antacids containing aluminium or magnesium hydroxides.

Concomitant administration of pseudoephedrine and fexofenadine hydrochloride does not affect the pharmacokinetics of each other.

Consumption of fruit juices, such as grapefruit, orange, and apple juice, may reduce the bioavailability of fexofenadine hydrochloride. Therefore, fexofenadine hydrochloride is recommended to be taken with water.

Special precautions for use

Fexofenadine hydrochloride should be used with caution in elderly patients and younger patients with pre-existing liver or kidney disease due to insufficient experience with fexofenadine hydrochloride in these patient groups.

Patients with cardiovascular disorders (including those with a history of such conditions) should be aware that antihistamine agents may cause adverse effects such as tachycardia and palpitations (see section "Adverse reactions").

The medicinal product contains lactose and therefore should not be administered to patients with rare hereditary problems of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

Use during pregnancy or breastfeeding

Pregnancy

Data on use in pregnant women are limited. Available animal studies do not indicate any direct or indirect harmful effects on pregnancy, embryonal/fetal development, parturition, or postnatal development. Fexofenadine hydrochloride should not be used during pregnancy unless the expected benefit to the mother clearly outweighs the potential risk to the fetus (should be used only when strictly necessary).

Breastfeeding period

Since fexofenadine is excreted into breast milk, it should not be used during breastfeeding.

Effects on ability to drive and use machines

Based on the pharmacodynamic profile and available data on adverse effects, fexofenadine hydrochloride has not shown any negative influence on the ability to drive a vehicle or operate machinery. Clinical studies have not revealed any significant effect of Fexofen-Sanovel on central nervous system function. Patients may drive cars or perform work requiring concentration.

However, since some patients may experience adverse reactions such as drowsiness, caution should be exercised when driving vehicles or operating machinery.

In patients with known hypersensitivity, it is recommended to assess individual response to the medicinal product before engaging in such activities.

Dosage and Administration.

Take tablets with water, regardless of food intake. The recommended dose for adults and children aged 12 years and older is 120 mg once daily (preferably in the morning). The duration of treatment is determined individually by a physician for each specific case and depends on the course of the disease.

Children.

This medicinal product at this dosage strength should not be used in children under 12 years of age.

Overdose.

Cases of dizziness, somnolence, increased fatigue, and dry mouth have been reported following overdose of fexofenadine hydrochloride. Compared with placebo, administration of the drug at doses up to 60 mg twice daily for 2 weeks in children, as well as single doses up to 800 mg and doses of 690 mg twice daily for 1 month or 240 mg once daily for 1 year in healthy volunteers, did not result in clinically significant adverse effects compared to placebo. The maximum tolerated dose of fexofenadine hydrochloride has not been established.

In case of significant overdose, symptomatic treatment and monitoring of vital functions are indicated. Measures aimed at removing unabsorbed active substances should be implemented. Hemodialysis is ineffective. To date, there is no known antidote for this drug.

Adverse Reactions

Adverse reactions observed in adults during controlled clinical trials are listed by system organ class and frequency of occurrence: 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), frequency not known (cannot be estimated based on available data).

Nervous system disorders: common – headache, somnolence, dizziness.

Gastrointestinal disorders: common – nausea; frequency not known – dry mouth.

General disorders and administration site conditions: uncommon – increased fatigue.

During post-marketing surveillance, the following adverse reactions have been reported in adults (frequency of occurrence is unknown and cannot be estimated based on available data):

Immune system disorders: hypersensitivity reactions manifested as angioedema, chest tightness, dyspnea, flushing sensation, and other systemic anaphylactic reactions.

Psychiatric disorders: insomnia, nervousness, increased nervous system excitability, sleep disturbances or nightmares/unusual dreams (distressing dreams).

Cardiac disorders: tachycardia, palpitations.

Gastrointestinal disorders: diarrhea.

Skin and subcutaneous tissue disorders: rash, urticaria, pruritus.

Patients with cardiovascular diseases (including those in medical history) should be aware that antihistamine class drugs may cause adverse effects such as tachycardia and rapid heartbeat; no significant effect of hydrochloride fexofenadine on QT interval has been observed.

Visual disturbances: frequency not known – blurred vision.

Other reported adverse reactions: dysmenorrhea, back pain, limb pain, pain, accidental injury, fever, otitis, upper respiratory tract infections, rhinorrhea, nasopharyngitis, cough, vomiting, dyspepsia, myalgia.

Reporting of suspected adverse reactions. Reporting of suspected adverse reactions after drug approval is an important procedure. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the national reporting system.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging, protected from light, in a place inaccessible to children, at a temperature not exceeding 25 °C.

Packaging. 10 tablets in a blister; 1 or 2 blisters per cardboard box.

Availability. Over-the-counter.

Manufacturer. Sanovel Ilac Sanaı ve Ticaret A.S.

Manufacturer's address and location of business activity.

Balaban district, Cihanger Sokagi, No. 10, Istanbul, 34580, Silivri, Turkey.