Fexofast

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FEXOFAST (FEXOFAST)

Composition:

Active substance: fexofenadine hydrochloride;

One film-coated tablet contains 120 mg or 180 mg of fexofenadine hydrochloride;

Excipients: microcrystalline cellulose, corn starch, lactose monohydrate, sodium croscarmellose, povidone, colloidal anhydrous silicon dioxide, magnesium stearate, talc, hypromellose, propylene glycol, titanium dioxide (E 171), yellow FCF (E 110) (180 mg tablets).

Pharmaceutical form. Film-coated tablets.

Main physico-chemical properties:

120 mg tablets: film-coated tablets, white or almost white, round, biconvex.

180 mg tablets: film-coated tablets, orange-colored, oblong.

Pharmacotherapeutic group. Antihistamines for systemic use.

ATC code R06AX26.

Pharmacological Properties

Pharmacodynamics

Fexofenadine hydrochloride is a non-sedating antihistamine belonging to the group of specific H1 receptor antagonists. Fexofenadine is the pharmacologically active metabolite of terfenadine. It stabilizes the membranes of mast cells and prevents the release of histamine. It relieves allergy symptoms such as sneezing, rhinorrhea, itching, eye redness, and lacrimation. It does not produce sedative effects.

The antihistaminic effect of fexofenadine hydrochloride administered once or twice daily appears within 1 hour, reaches its maximum at 6 hours, and lasts for 24 hours. There were no signs of developing tolerance, even after 28 days of treatment. Clinical effects were observed after single oral doses ranging from 10 to 130 mg. A dose of 120 mg is sufficient to ensure 24-hour efficacy.

Even at plasma concentrations 32 times higher than therapeutic levels, fexofenadine showed no effect on human cardiac slow potassium channels.

Fexofenadine hydrochloride (5–10 mg/kg orally) suppresses antigen-induced bronchospasm in sensitized animals. At concentrations above the therapeutic range (10–100 micromoles), it causes histamine release from peritoneal mast cells.

Pharmacokinetics

Fexofenadine hydrochloride is rapidly absorbed after oral administration. Maximum plasma concentration is reached approximately within 1–3 hours. At a daily dose of 120 mg, the mean maximum concentration is approximately 427 ng/mL. At a daily dose of 180 mg, the mean maximum 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 in the liver and extrahepatically). Only unchanged fexofenadine is found in significant amounts in human and animal urine and feces.

Elimination of fexofenadine from plasma follows a biexponential decline, with a terminal 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. At steady state, doses up to 240 mg twice daily resulted in an increase in AUC slightly greater than proportional (8.8%). This indicates that the pharmacokinetics of fexofenadine are nearly linear within the daily dose range of 40–240 mg.

The majority of the administered dose is excreted via bile and feces; up to 10% is excreted unchanged in urine.

Mutagenic and carcinogenic properties

Various mutagenicity tests in vitro and in vivo revealed no mutagenic properties of fexofenadine hydrochloride.

Carcinogenicity studies of fexofenadine hydrochloride were based on studies in which exposure to fexofenadine was determined (using plasma AUC metrics) following administration of terfenadine in secondary pharmacokinetic studies. No evidence of carcinogenicity was observed when terfenadine was administered to rats and mice at doses up to 150 mg/kg body weight per day.

Clinical characteristics.

Indications.

120 mg tablets: symptomatic treatment of seasonal allergic rhinitis in adults and children aged 12 years and older.

180 mg tablets: symptomatic treatment of chronic idiopathic urticaria in adults and children aged 12 years and older.

Contraindications.

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

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.

Fexofenadine is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP). Concomitant administration of fexofenadine with P-gp inhibitors or inducers may affect fexofenadine exposure. It has been established that concomitant administration of fexofenadine hydrochloride with the P-gp inhibitors erythromycin or ketoconazole leads to a 2- to 3-fold increase in plasma fexofenadine levels. 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 the medicinal products administered separately.

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

No interaction was observed with omeprazole.

Administration of antacids containing aluminium or magnesium hydroxides 15 minutes prior to taking the 180 mg Fexofast tablet reduces the bioavailability of fexofenadine hydrochloride due to its binding in the gastrointestinal tract. A two-hour interval should be maintained between the administration of fexofenadine hydrochloride and antacids containing aluminium or magnesium hydroxides.

Special precautions for use

Fexofast should be used with caution in elderly patients and in patients with hepatic or renal impairment due to insufficient experience with the use of fexofenadine hydrochloride in these patient groups.

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 reactions").

The product contains lactose; therefore, it should not be used in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption syndrome.

Use during pregnancy or breast-feeding.

Pregnancy

Data on use in pregnant women are limited. Animal studies have not shown any direct or indirect harmful effects on pregnancy, embryonal/fetal development, parturition or postnatal development. Fexofenadine hydrochloride may be used during pregnancy only if clearly needed, when the potential benefit justifies the potential risk to the fetus.

Breast-feeding period

Since fexofenadine is excreted in breast milk, the drug should not be used during breast-feeding.

Ability to influence the speed of reactions 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. Patients may drive cars or perform tasks requiring mental concentration. However, since some patients may experience adverse reactions such as drowsiness, caution should be exercised when driving or operating machinery.

Patients taking Fexofast are advised to assess their individual response to the medicine before driving or operating vehicles or machinery.

Method of Administration and Dosage

Film-coated tablets should be swallowed whole, before meals, without chewing, with water.

For adults and children aged 12 years and older:

• For symptomatic treatment of seasonal allergic rhinitis: 1 tablet of 120 mg once daily;
• For symptomatic treatment of chronic idiopathic urticaria: 1 tablet of 180 mg once daily.

At-risk Groups

Dosage adjustment is not required for elderly patients or patients with impaired renal or hepatic function.

The duration of treatment is determined by the physician depending on the course of the disease.

Children

The drug must not be used in children under 12 years of age.

Overdose

Cases of dizziness, drowsiness, and dry mouth have been reported following overdose of hydrochloride fexofenadine. Compared to placebo, single doses up to 800 mg, doses of 690 mg twice daily for 1 month, and 240 mg once daily for 1 year have been administered to healthy volunteers without any clinically significant adverse effects. The maximum tolerated dose of fexofenadine hydrochloride has not been established.

In case of overdose, standard measures (e.g., gastric lavage) should be taken to remove the drug. Symptomatic and supportive therapy is recommended. Hemodialysis is not effective for removing fexofenadine from the blood.

Adverse Reactions

Adverse reactions observed during clinical trials are categorized by organ system 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).

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

From the gastrointestinal tract.
Common: nausea.

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

During post-marketing surveillance, the following adverse effects have been reported in adults (frequency unknown):

From the immune system.
Hypersensitivity reactions manifested as angioneurotic edema, chest tightness, dyspnea, hot flushes, and systemic anaphylaxis.

From the psyche.
Insomnia, increased nervous system excitability, sleep disturbances, or nightmares/unusual dreams (painful dreams).

From the heart.
Tachycardia, palpitations.

From the gastrointestinal tract.
Diarrhea.

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

Visual disturbances.
Blurred vision.

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25°C. Keep out of reach of children.

Packaging. 10 tablets in a blister pack; 1 or 3 blisters per cardboard box.

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

Manufacturer. Micro Labs Limited

Manufacturer's address and site of operations.
92, Sipcot Industrial Complex, Hosur, Tamil Nadu, IN–635 126, India / 92, Sipcot Industrial Complex, Hosur, Tamil Nadu, IN-635 126, India