Alteva

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ALTVIA (ALTIVA)

Composition:

Active ingredient: fexofenadine hydrochloride;

1 coated tablet contains 180 mg of fexofenadine hydrochloride;

Excipients: sodium carboxymethylcellulose, microcrystalline cellulose, pregelatinized starch, colloidal anhydrous silicon dioxide, povidone, magnesium stearate, hydroxypropylmethylcellulose, titanium dioxide (E171), propylene glycol, iron oxide red (E172).

Pharmaceutical form. Coated tablets.

Main physicochemical properties: oval-shaped, peach-colored coated tablets; on one side of the tablet, the marking "ALTIVA180" is printed in black ink.

Pharmacotherapeutic group. Systemic antihistamines.

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 assessing histamine-induced skin wheal and erythema, the antihistaminic effect of fexofenadine hydrochloride administered once or twice daily was evident within 1 hour, reached its maximum at 6 hours, and persisted for up to 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 ensure a continuous 24-hour effect. The maximum inhibition of wheal and erythema exceeded 80%.

In patients with seasonal allergic rhinitis who received 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 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 human cardiac slow potassium channels.

Pharmacokinetics

Fexofenadine hydrochloride is rapidly absorbed after oral administration. Maximum plasma concentration is reached within approximately 1 to 3 hours. At a daily dose of 180 mg, the mean maximum concentration is approximately 494 ng/mL.

Fexofenadine is 60–70% 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 ranging from 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 doses up to 240 mg twice daily, saturation occurs, resulting 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.

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 chronic idiopathic urticaria.

Contraindications.

Hypersensitivity to fexofenadine hydrochloride and terfenadine 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 mechanism.

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 results in a 2- to 3-fold increase in plasma concentrations 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 the medicinal products administered separately.

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

No interaction was observed between fexofenadine and omeprazole.

However, administration of an antacid containing aluminum and magnesium hydroxide 15 minutes prior to fexofenadine hydrochloride resulted in reduced bioavailability, most likely due to binding in the gastrointestinal tract. It is advisable to maintain a 2-hour interval between administration of fexofenadine hydrochloride and antacids containing aluminum and magnesium hydroxide.

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 should be taken with water.

Special precautions for use

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

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

Use during pregnancy or breastfeeding

Pregnancy

Data on the use of fexofenadine hydrochloride in pregnant women are insufficient. Limited animal studies do not indicate any direct or indirect adverse effects on pregnancy, embryonal/foetal development, parturition, or postnatal development. Fexofenadine hydrochloride should not be used during pregnancy except when clearly necessary and when the potential benefit to the mother outweighs the possible risk to the foetus.

Breastfeeding period

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

Ability to influence reaction capacity while driving or operating machinery

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

However, in individual patients with increased sensitivity to the drug, it is recommended to assess their personal response to the medicinal product before driving or performing such tasks.

Method of Administration and Dosage

The following doses are recommended:

Adults:

The recommended dose of fexofenadine hydrochloride for adults is 180 mg once daily.

Children:

Children aged 12 years and older

The recommended dose of fexofenadine hydrochloride for children aged 12 years and older is 180 mg once daily.

Children under 12 years of age

No studies on the efficacy and tolerability of Altiva 180 mg have been conducted in children under 12 years of age.

Special Populations:

Based on study results in patients from certain risk groups (elderly patients, patients with renal or hepatic impairment), dosage adjustment is not required for these patients.

The duration of treatment depends on the course of the disease and is determined individually by the physician.

Children

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

Overdose

Cases of dizziness, somnolence, and dry mouth have been reported following fexofenadine hydrochloride overdose. Compared with placebo, single doses up to 800 mg, doses of 690 mg twice daily for 1 month, and doses of 240 mg once daily for 1 year have been administered to healthy volunteers without any clinically significant adverse effects.

In case of overdose, standard measures aimed at removing unabsorbed active substances should be applied. Symptomatic and supportive therapy is recommended. Hemodialysis is ineffective for removing fexofenadine hydrochloride from blood.

In a study involving 40 patients who received fexofenadine hydrochloride 400 mg every 12 hours for 6.5 days, no clinically significant adverse reactions were observed.

Adverse Reactions

From the nervous system: headache, drowsiness, dizziness.

From the visual system: frequency unknown: blurred vision.

From the gastrointestinal tract: nausea.

General disorders and administration site reactions: increased fatigue.

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

From the immune system: hypersensitivity reactions manifested as angioneurotic edema, chest tightness, dyspnea, sensation of warmth, and systemic anaphylaxis.

From the psychiatric side: insomnia, increased nervous system excitability, sleep disorders or nightmares/unusual dreams (painful dreams).

From the cardiac side: tachycardia, palpitations.

From the gastrointestinal tract: diarrhea.

From the skin and subcutaneous tissue: rash, urticaria, pruritus.

Patients with past or current cardiovascular diseases should be aware that antihistamine class drugs may contribute to adverse effects such as tachycardia and rapid heartbeat. No significant effect of hydrochloride fexofenadine on the QT interval has been observed.

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

Shelf life. 2 years.

Storage conditions.

Store in a dry place, out of reach of children, at a temperature not exceeding 25 °C.

Packaging.

10 tablets in a blister; 1 blister per cardboard pack.

Category of release.

Over-the-counter.

Manufacturer.

Sun Pharmaceutical Industries Limited.

Manufacturer's address and location of business operation.

Industrial Area 3, Dewas - 455001, India /
Industrial Area 3, Dewas, 455001, India.