Allegra (Tablets) Instructions for Use

Marketing Authorization Holder

A. Nattermann and Cie., GmbH (Germany)

Manufactured By

Sanofi Winthrop Industrie (France)

Contact Information

OPELLA HEALTHCARE LLC (Russia)

ATC Code

R06AX26 (Fexofenadine)

Active Substance

Fexofenadine (Rec.INN registered by WHO)

Dosage Forms

	Allegra	Film-coated tablets, 120 mg: 10 pcs.
		Film-coated tablets, 180 mg: 10 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets light pink in color, oblong, biconvex, with an engraving of “012” on one side and a stylized “e” on the other.

Excipients: croscarmellose sodium, pregelatinized starch, microcrystalline cellulose pH101, microcrystalline cellulose pH102, magnesium stearate.

Shell composition: hypromellose E-15, hypromellose E-5, povidone K30, titanium dioxide (E171), colloidal silicon dioxide, macrogol 400, iron oxide pigment (pink mixture*), iron oxide pigment (yellow mixture**).

10 pcs. – blisters (1) – cardboard packs.

Film-coated tablets light pink in color, oblong, biconvex, with an engraving of “018” on one side and a stylized “e” on the other.

Excipients: croscarmellose sodium, pregelatinized starch, microcrystalline cellulose pH101, microcrystalline cellulose pH102, magnesium stearate.

Shell composition: hypromellose E-15, hypromellose E-5, povidone K30, titanium dioxide (E171), colloidal silicon dioxide, macrogol 400, iron oxide pigment (pink mixture*), iron oxide pigment (yellow mixture**).

10 pcs. – blisters (1) – cardboard packs.

* The pink iron oxide pigment mixture is a mixture of red iron oxide (E172) and titanium dioxide (E171).
** The yellow iron oxide pigment mixture is a mixture of yellow iron oxide (E172) and titanium dioxide (E171).

Clinical-Pharmacological Group

Histamine H₁-receptor blocker. Antiallergic drug

Pharmacotherapeutic Group

Systemic antihistamines; other systemic antihistamines

Pharmacological Action

Fexofenadine (a pharmacologically active metabolite of terfenadine) is an antihistamine with selective antagonistic activity at histamine H₁-receptors without anticholinergic and alpha-adrenergic blocking effects. Furthermore, fexofenadine does not exhibit sedative effects or other central nervous system effects.

In human studies evaluating histamine-induced wheals and erythema, the antihistamine effect of orally administered fexofenadine, taken once or twice daily, appears within 1 hour, peaks at 6 hours, and lasts for 24 hours after its administration. Even after 28 days of fexofenadine administration, no development of tolerance to the drug was detected. With a single oral dose of fexofenadine, a dose-dependent increase in the antihistamine effect was observed when the dose was increased from 10 mg to 130 mg. Using the same model of antihistamine action, it was established that a dose of at least 130 mg was necessary for a constant 24-hour effect. The maximum suppression of wheal and erythema formation is over 80%.

In patients with seasonal allergic rhinitis receiving up to 240 mg of fexofenadine twice daily for 2 weeks, the QTc interval duration did not differ from that with placebo.

No changes in QTc were observed in healthy volunteers taking fexofenadine at 60 mg twice daily for 6 months, 400 mg twice daily for 6.5 days, and 240 mg/day for 1 year compared to the QTc duration with placebo.

Even at plasma concentrations 32 times higher than therapeutic concentrations in humans, Fexofenadine had no effect on the delayed rectifier potassium channels in the human heart.

Pharmacokinetics

Absorption and Distribution

Fexofenadine is rapidly absorbed after oral administration, with T_max being approximately 1-3 hours. The mean C_max value when taking 120 mg/day is approximately 289 ng/ml, and when taking 180 mg/day is approximately 494 ng/ml.

The pharmacokinetics of fexofenadine after single and course administration (orally up to 120 mg twice daily) are linear. At a dose of 240 mg twice daily, a slightly more than proportional (by 8.8%) increase in AUC is observed, indicating that the pharmacokinetics of fexofenadine are practically linear in the dose range from 40 to 240 mg/day.

The binding of fexofenadine to plasma proteins is 60-70%.

Metabolism

Fexofenadine is minimally metabolized in the liver and elsewhere, as confirmed by it being the only substance detected in significant amounts in human and animal urine and feces.

Excretion

With course administration of the drug, the plasma elimination curve of fexofenadine declines biexponentially, and the terminal T_1/2 is 11-15 hours.

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

Indications

• Seasonal allergic rhinitis (for symptom relief) – 120 mg tablets;
• Chronic idiopathic urticaria (for symptom relief) – 180 mg tablets.

ICD codes

Dosage Regimen

The drug is intended for oral administration.

The recommended dose of fexofenadine for seasonal allergic rhinitisfor adults and children aged 12 years and older is 120 mg once daily before meals.

The recommended dose of fexofenadine for chronic urticaria for adults and children aged 12 years and older is 180 mg once daily before meals.

Patients at risk

Studies in special risk groups ( elderly patients, patients with renal and hepatic impairment) have shown that no adjustment of the dosing regimen is required for them.

If no improvement occurs after treatment, or symptoms worsen, or new symptoms appear, it is necessary to consult a doctor. The drug should be taken only according to the indications, method of administration, and doses specified in the instructions.

Adverse Reactions

In placebo-controlled clinical studies, the most common (≥1%, <10%) adverse reactions observed were: headache (7.3%), drowsiness (2.3%), dizziness (1.5%), and nausea (1.5%). The frequency of the aforementioned adverse effects with fexofenadine was similar to that with placebo.

In placebo-controlled studies with a frequency of less than 1% (equally with fexofenadine and placebo) and during post-marketing use, the following were observed: weakness, insomnia, nervousness, and sleep disorders or unusual dreams (paroniria), such as nightmares; tachycardia, palpitations; diarrhea.

In rare cases (≥0.01%, <0.1%): exanthema, urticaria, pruritus, and other hypersensitivity reactions, such as angioedema, difficulty breathing, shortness of breath, skin flushing, systemic anaphylactic reactions.

If the adverse reactions listed in the instructions occur, or they worsen, or any other adverse reactions not listed in the instructions occur, the patient should inform the doctor.

Contraindications

• Hypersensitivity to any component of the drug;
• Pregnancy;
• Breastfeeding period;
• Children under 12 years of age.

With caution

• In patients with chronic renal and hepatic impairment, as well as in elderly patients (insufficient clinical experience of use in this category of patients);
• In patients with cardiovascular diseases, including in the medical history (antihistamines may cause palpitations and tachycardia) (see section “Adverse Reactions”).

Use in Pregnancy and Lactation

Pregnancy

There is insufficient data on the use of fexofenadine in pregnant women. Limited animal studies have shown no evidence of adverse effects on pregnancy, embryonic/fetal development, childbirth, or postnatal development. Fexofenadine is contraindicated for use during pregnancy.

Breastfeeding period

Data on the content of fexofenadine in breast milk when taken by women during breastfeeding are not available. However, it has been shown that terfenadine is excreted in breast milk in women. Therefore, the use of fexofenadine during breastfeeding is contraindicated.

Use in Hepatic Impairment

The drug should be prescribed with caution in chronic hepatic impairment. No dose adjustment is required.

Use in Renal Impairment

The drug should be prescribed with caution in chronic renal impairment. No dose adjustment is required.

Pediatric Use

Contraindicated in children under 12 years of age.

Geriatric Use

The drug should be prescribed with caution in elderly patients (insufficient clinical experience of use in this category of patients). No dose adjustment is required.

Special Precautions

It is recommended that the time interval between taking fexofenadine and antacids containing aluminum or magnesium hydroxide be at least 2 hours.

Use in pediatrics

For use in children aged 6 to 11 years, 30 mg tablets are available.

Effect on ability to drive vehicles and operate machinery

When taking the drug, it is possible to perform work requiring high concentration and speed of psychomotor reactions (except for patients with an atypical reaction). Therefore, it is recommended to check the individual reaction to fexofenadine before engaging in such activities.

Overdose

Symptoms: dizziness, drowsiness, and dry mouth. Healthy volunteers have taken single doses up to 800 mg and course doses up to 690 mg twice daily for 1 month or 240 mg twice daily for 1 year without any significant adverse effects compared to placebo. The maximum tolerated dose for fexofenadine has not been established.

Treatment: in case of overdose, gastric lavage, administration of activated charcoal, and if necessary, symptomatic and supportive therapy are recommended. Hemodialysis is not effective.

Drug Interactions

When fexofenadine is used concomitantly with erythromycin or ketoconazole, the plasma concentration of fexofenadine increases 2-3 times, but this is not accompanied by a significant prolongation of the QTc interval. No significant differences in the frequency of adverse effects were observed when these drugs were used as monotherapy and as part of combination therapy. Animal studies have shown that the aforementioned increase in fexofenadine plasma concentrations is likely due to improved absorption of fexofenadine and reduced biliary excretion or secretion into the gastrointestinal lumen.

No interaction is observed between fexofenadine and omeprazole.

Does not interact with drugs metabolized in the liver.

Taking aluminum- or magnesium-containing antacids 15 minutes before taking fexofenadine leads to a decrease in the bioavailability of the latter, apparently due to binding in the gastrointestinal tract.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 3 years.

Dispensing Status

The drug is dispensed without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.