Allegra® 120 mg

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ALLEGRA® 120 mg (ALLEGRA® 120 mg)

Composition:

Active substance:
fexofenadine hydrochloride;

1 tablet contains fexofenadine hydrochloride 120 mg (equivalent to 112 mg of fexofenadine);

Excipients:
microcrystalline cellulose, pregelatinized starch, sodium croscarmellose, magnesium stearate;

Coating:
hypromellose, polyethylene glycol 400, titanium dioxide (E 171), colloidal anhydrous silicon dioxide, povidone, mixture of yellow iron oxide (E 172) and pink iron oxide (E 172).

Pharmaceutical form.
Film-coated tablets.

Main physicochemical properties:
Peach-colored, modified capsule-shaped, film-coated tablets, with an embossing “

012

” on one side and a capital letter “e” on the other side.

Pharmacotherapeutic group.
Antihistamines for systemic use. ATC code: R06AX26.

Pharmacological Properties.

Pharmacodynamics.
Fexofenadine hydrochloride is a nonsedating antihistamine agent belonging to the class of specific H1-receptor antagonists. 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, reaching maximum effect at 6 hours and lasting for 24 hours. There was no evidence of tachyphylaxis, even after 28 days of treatment. Clinical effects were observed following 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. Maximum inhibition of wheal and flare exceeded 80%. Clinical studies in seasonal allergic rhinitis indicate that a 120 mg dose is sufficient to provide 24-hour efficacy.

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

Similarly, no such changes were observed compared to placebo in healthy volunteers receiving 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 QT interval changes were observed compared to placebo after administration of fexofenadine hydrochloride 60 mg twice daily for 2 weeks.

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

Pharmacokinetics.
Fexofenadine hydrochloride is rapidly absorbed after oral administration. Peak plasma concentration is reached within approximately 1–3 hours. Peak 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 compound is predominantly excreted unchanged in urine and feces. Elimination of fexofenadine from plasma follows a biphasic pattern, with a terminal elimination half-life of 11 to 15 hours after repeated dosing. The pharmacokinetics 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 via bile; 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.

Contraindications.

Hypersensitivity to fexofenadine hydrochloride or to any of the excipients of the medicinal product.

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

Special precautions.

Caution should be exercised when administering Allegra® 120 mg to elderly patients and patients with impaired hepatic or renal function due to insufficient data.

Patients with a history of, or current, cardiovascular disorders should be aware that antihistamine agents may contribute to adverse effects such as tachycardia and palpitations (see section "Adverse effects").

Interaction with other medicinal products and other types of interactions.

Fexofenadine is not metabolized in the liver and therefore does not interact with other medicinal products via this route.

Combinations requiring precaution during use

When administered concomitantly with erythromycin or ketoconazole, a 2−3-fold increase in plasma concentration of fexofenadine has been observed. The effect on the QT interval was not associated with this change; the frequency of adverse reactions did not increase compared to that observed with administration of each of these substances separately. Animal studies have shown that the increased plasma concentration of fexofenadine observed after concomitant administration of erythromycin or ketoconazole may be due to increased gastrointestinal absorption of the drug and/or reduced excretion via the biliary tract or decreased gastrointestinal secretion.

No interaction with omeprazole has been observed.

Gastrointestinal agents with local action, antacids and adsorbents. Administration of antacids containing aluminium or magnesium hydroxides 15 minutes prior to taking Allegra® 120 mg reduces the bioavailability of fexofenadine hydrochloride, likely due to binding in the gastrointestinal tract, thereby decreasing gastrointestinal absorption of fexofenadine. An interval (preferably longer than 2 hours) should be maintained between the administration of fexofenadine hydrochloride and gastrointestinal agents with local action.

Special precautions for use.

Use during pregnancy or breastfeeding.

Pregnancy.
Data on use in pregnant women are insufficient. Limited animal studies do not indicate any direct or indirect adverse effects on pregnancy, embryonic/fetal development, delivery, or postnatal development. Fexofenadine hydrochloride should not be used during pregnancy except in cases of urgent medical need, when the expected benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding.
Since fexofenadine is excreted in breast milk, Allegra® 120 mg should not be used during breastfeeding.

Ability to influence reaction rate while driving or operating machinery.

Based on the pharmacodynamic profile and currently available data on adverse effects, fexofenadine hydrochloride has not been shown to negatively affect the ability to drive a vehicle or operate machinery. Clinical studies have demonstrated no significant effect of Allegra® 120 mg on central nervous system function. Patients may drive vehicles or perform tasks requiring concentration.

However, in individuals with increased sensitivity to the drug, it is recommended to first assess individual response to the medication.

Dosage and Administration.

The recommended dose of fexofenadine hydrochloride for adults and children aged 12 years and older is 120 mg once daily, i.e. one 120 mg tablet taken once per day.

Administration method
: Oral administration.

Children
The drug is not recommended for children under 12 years of age.

Overdose
Cases of dizziness, somnolence, increased fatigue, and dry mouth have been reported following fexofenadine hydrochloride overdose. Compared to placebo, 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 cause any clinically significant adverse effects. The maximum tolerated dose of fexofenadine hydrochloride has not been established.

In case of significant overdose, symptomatic treatment should be administered and vital functions should be monitored. Hemodialysis is ineffective in removing fexofenadine hydrochloride from blood. There is currently no known antidote for the drug.

Adverse Reactions

Adverse reactions observed in adults during controlled clinical trials are categorized by organ systems and frequency of occurrence: very common (> 1/10), common (> 1/100, < 1/10), uncommon (> 1/1000, < 1/100), rare (> 1/10000, < 1/1000), very rare (< 1/10000), frequency not known.

From the nervous system.
Common: headache, somnolence, dizziness.

From the gastrointestinal tract.
Common: nausea. Frequency not known: dry mouth.

General disorders and administration site reactions.
Uncommon: increased fatigue.

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

From the immune system.
Hypersensitivity reactions manifested as angioneurotic edema, chest tightness, dyspnea, flushing sensations, and other systemic anaphylactic reactions.

From the psyche.
Insomnia, nervousness, sleep disorders, or nightmares/unusual dreams (distressing dreams).

From the heart.
Tachycardia, palpitations.

From the gastrointestinal tract.
Diarrhea.

From the skin and subcutaneous tissue.
Rash, urticaria, pruritus.

Reporting of suspected adverse reactions.
Reporting suspected adverse reactions after a medicinal product has been authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are encouraged to report any suspected adverse reactions through the national reporting system.

Shelf life.
3 years.

Storage conditions.
Store at temperatures not exceeding 25 °C. Keep out of the reach of children.

Packaging.
No. 10, No. 20 (10×2); 10 tablets in a blister; 1 or 2 blisters in a cardboard box.

Availability.
Over-the-counter (without prescription).

Manufacturer.
Sanofi Winthrop Industrie, France / Sanofi Winthrop Industrie, France.

Manufacturer's address and location of operations.
30 Avenue Gustave Eiffel, Tours, 37100, France / 30 Avenue Gustave Eiffel, Tours, 37100, France.

Marketing Authorization Holder.
Opella Healthcare Ukraine LLC, Ukraine / Opella Healthcare Ukraine LLC, Ukraine.