Allegra® 180 mg

INSTRUCTION for medical use of the medicinal product ALLEGRA® 180 mg (ALLEGRA® 180 mg)

Composition:

Active substance:
fexofenadine hydrochloride;

One tablet contains fexofenadine hydrochloride 180 mg (equivalent to 168 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, yellow iron oxide mixture (E 172) and pink iron oxide mixture (E 172).

Pharmaceutical form.
Film-coated tablets.

Main physicochemical properties:
Peach-colored, capsule-shaped film-coated tablets, with embossing “018” on one side and uppercase letter “e” on the other side.

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

Pharmacological Properties

Pharmacodynamics

Fexofenadine hydrochloride is a nonsedating antihistamine belonging to the class of specific H1-receptor antagonists. Fexofenadine is the pharmacologically active metabolite of terfenadine.

In clinical studies of histamine-induced skin wheals and erythema, the antihistaminic effect of fexofenadine hydrochloride administered once or twice daily became evident within 1 hour, reached its maximum at 6 hours, and persisted for 24 hours. There was no evidence of tachyphylaxis even after 28 days of treatment. Clinical effects were 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 erythema exceeded 80%.

In patients with seasonal allergic rhinitis receiving fexofenadine hydrochloride 240 mg 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 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.

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. At a daily dose of 180 mg, the mean peak plasma concentration is approximately 494 ng/mL.

60–70% of fexofenadine is bound to plasma proteins. The active substance does not cross the blood-brain barrier.

Fexofenadine undergoes minimal metabolism (both hepatic and extrahepatic); only unchanged fexofenadine is found in significant amounts in human urine and feces.

Elimination of fexofenadine from plasma follows a biexponential decline with a terminal elimination half-life of 11 to 15 hours after multiple dosing. The kinetics of single and multiple doses are linear at oral doses up to 120 mg twice daily. At steady state, doses up to 240 mg twice daily resulted in an increase in AUC slightly greater than proportional (8.8%), indicating that the pharmacokinetics of fexofenadine are nearly linear over the daily dose range of 40–240 mg.

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

Clinical characteristics.

Indications. Symptomatic treatment of chronic idiopathic urticaria in adults and children aged 12 years and older.

Contraindications. Hypersensitivity to any component of the medicinal product.

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

Special safety precautions.

Caution should be exercised when administering Allegra® 180 mg to elderly patients and patients with impaired hepatic or renal function due to insufficient data.

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

Interaction with other medicinal products and other forms of interaction.

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

Combinations requiring precaution during use

A 2−3-fold increase in plasma concentration of fexofenadine has been observed when administered concomitantly with erythromycin or ketoconazole. This change was not associated with effects on the QT interval; the incidence of adverse reactions was not increased compared to administration of each of these agents separately.

Animal studies have shown that the increased plasma concentration of fexofenadine observed after co-administration with erythromycin or ketoconazole may be due to increased gastrointestinal absorption of the drug and/or reduced excretion or secretion into the bile ducts or gastrointestinal tract.

No interaction with omeprazole has been observed.

Locally acting gastrointestinal agents, antacids, and adsorbents. Administration of antacids containing aluminum or magnesium hydroxides 15 minutes prior to taking Allegra® 180 mg reduces the bioavailability of fexofenadine hydrochloride, likely due to binding in the gastrointestinal tract, thereby decreasing fexofenadine absorption. An interval (preferably longer than 2 hours) should be maintained between administration of fexofenadine hydrochloride and locally acting gastrointestinal agents.

Special warnings.

Use during pregnancy or breastfeeding.

Pregnancy. Data on use in pregnant women are insufficient. Limited animal studies do not indicate a direct or indirect harmful effect on pregnancy, embryonic/fetal development, labor, 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 – only in cases of extreme necessity.

Breastfeeding. Since fexofenadine passes into breast milk, Allegra® 180 mg should not be used during breastfeeding.

Ability to influence reaction speed when driving or operating machinery.

Based on the pharmacodynamic profile and current data on adverse effects, fexofenadine hydrochloride has not shown a negative impact on the ability to drive a vehicle or operate machinery. Clinical trials have not revealed any significant effect of Allegra® 180 mg on central nervous system function. Patients may drive vehicles or perform tasks requiring concentration.

However, in cases of increased individual sensitivity to the medicinal product, it is recommended to first assess the patient's individual response to the drug.

Dosage and Administration.

The recommended dose of fexofenadine hydrochloride for adults and children aged 12 years and older is 180 mg once daily, i.e., one 180 mg tablet taken once per day.

Children.

Do not use in 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, and 240 mg once daily for 1 year in healthy volunteers, did not result in any clinically significant adverse effects. The maximum tolerated dose of fexofenadine hydrochloride has not yet been established.

In case of significant overdose, symptomatic treatment should be administered and vital functions should be monitored. Removal of fexofenadine hydrochloride from blood by hemodialysis is ineffective. There is currently no known antidote for this 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.

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 effects have been reported in adults (the frequency of these effects 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, sleep disorders, or nightmares/unusual dreams (disturbing dreams).

Cardiac disorders.
Tachycardia, palpitations.

Gastrointestinal disorders.
Diarrhea.

Skin and subcutaneous tissue disorders.
Rash, urticaria, pruritus.

Reporting of suspected adverse reactions.
Reporting suspected adverse reactions after marketing authorization is an important procedure. It allows continuous 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 at temperatures not exceeding 25 °C. Keep out of reach of children.

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

Dispensing category.
Over-the-counter (without prescription).

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

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

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