Foratek

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

Composition:

Active substance: formoterol fumarate dihydrate;

1 dose of the preparation contains: formoterol fumarate dihydrate 12 mcg;

Excipients: ethanol anhydrous, lecithin, tetrafluoroethane (HFA-134a).

Pharmaceutical form. Aerosol (suspension) for inhalation.

Main physicochemical properties: white-colored suspension.

Pharmacotherapeutic group.
Agents used in obstructive airway diseases. Selective β2-adrenoreceptor agonists. ATC code: R03AC13.

Pharmacological properties.

Pharmacodynamics.

Formoterol fumarate is a selective β2-adrenergic agonist. In patients with reversible airway obstruction, it produces a rapid bronchodilator effect (within 1–3 minutes) that lasts for 12 hours after inhalation. The effect of therapeutic doses on the cardiovascular system is minimal and occurs only in isolated cases.

Formoterol inhibits the release of histamines and leukotrienes from passively sensitized human lung tissue. Some anti-inflammatory properties have been observed, such as inhibition of edema and inflammatory cell accumulation.

Pharmacokinetics.

Like other inhaled drugs, approximately 90% of formoterol administered via inhaler is swallowed and subsequently absorbed from the gastrointestinal tract. Therefore, the pharmacokinetic characteristics of orally administered formoterol largely also apply to the inhaled aerosol.

Oral doses of formoterol fumarate up to 300 μg are rapidly absorbed from the gastrointestinal tract. The maximum plasma concentration (Cmax) of unchanged drug is reached within 0.5–1 hour. The extent of absorption of an 80 μg oral dose is about 65%.

Formoterol pharmacokinetics are linear within the range of oral doses studied (20–300 μg). Repeated administration of oral daily doses of 40–160 μg does not lead to significant drug accumulation in the body. After inhaled administration at therapeutic doses, formoterol cannot be detected in plasma using currently available analytical methods. However, urinary excretion rates indicate rapid absorption following inhalation. Maximum excretion rates after doses of 12–96 μg were generally achieved within 1–2 hours.

Cumulative urinary excretion of formoterol after inhalation (12–24 μg) and from two aerosol formulations (12–96 μg) demonstrates that the amount of formoterol in blood increases proportionally with dose.

Plasma protein binding is 61–64% (of which 34% is to albumin), so binding sites are not saturated at concentrations achieved with therapeutic doses.

Formoterol is eliminated primarily via metabolism, mainly by direct glucuronidation of the molecule. Another elimination pathway is O-demethylation followed by glucuronidation.

Formoterol may be eliminated in multiple phases, and the actual elimination half-life depends on the dosing interval. Based on plasma concentrations measured 6, 8, or 12 hours after oral administration, the elimination half-life was determined to be 2–3 hours. The half-life determined from urinary excretion rates between 3–16 hours after inhalation was approximately 5 hours.

Both the active substance and its metabolites are completely eliminated from the body; approximately two-thirds of the orally administered dose is recovered in urine and one-third in feces. After inhalation, on average, approximately 6–9% of the dose is excreted unchanged in urine.

Renal clearance of formoterol is 150 mL/min.

Clinical characteristics.

Indications.

Treatment of bronchial asthma in patients who are using inhaled corticosteroids or who require treatment with long-acting β2-agonists.

Reduction of airway obstruction symptoms in patients with chronic obstructive pulmonary disease (COPD) who require treatment with long-acting β2-agonists.

Contraindications.

Hypersensitivity to formoterol or to any of the components of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

The use of drugs such as quinidine, disopyramide, procainamide, phenothiazines, antihistamines, tricyclic antidepressants, and erythromycin may be associated with QT interval prolongation and increased risk of ventricular arrhythmia (see section "Special precautions for use").

Concomitant use of sympathomimetic agents may enhance adverse reactions of the medicinal product and may require dose titration.

Formoterol should be administered with caution to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants, as they may potentiate the cardiovascular effects of β2-adrenergic stimulants.

Concomitant treatment with xanthine derivatives, steroids, or diuretics may enhance the hypokalaemic effect of β2-agonists. Hypokalaemia increases susceptibility to cardiac arrhythmias in patients taking digitalis (see section "Special precautions for use").

The risk of developing arrhythmias is increased during anaesthesia with halogenated hydrocarbon agents.

The bronchodilator effect of formoterol may be enhanced by concomitant use of anticholinergic agents.

β-adrenergic blockers may attenuate or abolish the effect of formoterol; therefore, β-blockers (including ophthalmic drops) should not be co-administered with formoterol, except when no alternative is available.

Special precautions for use.

Fatal outcome associated with bronchial asthma.

Formoterol fumarate dihydrate belongs to the class of long-acting β2-adrenergic receptor agonists. In studies with salmeterol, another long-acting β2-agonist, a higher incidence of fatal outcomes related to bronchial asthma was observed in the active treatment group (13/13,176) compared to the placebo group (3/13,179). Adequate studies have not been conducted to determine whether the frequency of fatal outcomes associated with bronchial asthma increases when using a medicinal product containing formoterol.

Treatment of asthma

Long-acting β2-agonists are not indicated (and are insufficient) for the primary treatment of asthma.

When treating patients with bronchial asthma, formoterol should only be used as an add-on therapy in combination with inhaled corticosteroids: in patients whose asthma is not adequately controlled by inhaled corticosteroids alone, or in patients in whom disease exacerbations warrant initiating treatment with inhaled corticosteroids and a long-acting β2-adrenergic stimulant.

Formoterol is not intended for use in children under 6 years of age due to insufficient experience with its use in this age group. In children aged 6 to 12 years, a combination product containing inhaled corticosteroids and a long-acting β2-adrenergic stimulant is recommended, except in cases where separate administration of inhaled corticosteroids and a long-acting β2-adrenergic stimulant is required.

Formoterol should not be used concomitantly with other long-acting β2-adrenergic stimulants.

Before prescribing formoterol, the patient's condition should be assessed to determine whether adequate anti-inflammatory treatment is being received. Patients should be advised to continue anti-inflammatory therapy after initiating formoterol, even if symptom improvement is observed.

The daily dose of Foratec should not exceed the maximum recommended dose (see section "Dosage and administration").

When symptoms of bronchial asthma are under control, a gradual reduction in the formoterol dose should be considered. During dose reduction, the patient's condition should be monitored regularly. The lowest effective dose of formoterol should be used.

There is a risk of serious adverse effects and asthma exacerbations during treatment with formoterol. Clinical trials using formoterol have indicated a higher frequency of severe exacerbations of bronchial asthma in patients receiving formoterol compared to those receiving placebo, particularly in children aged 5 to 12 years. These studies do not allow precise determination of differences in the frequency of asthma exacerbations between the study groups.

If symptoms persist or the number of formoterol doses required to control disease symptoms increases, this typically indicates worsening of the underlying condition and the need for a physician to reassess the baseline therapy for bronchial asthma.

Patients should not initiate treatment with formoterol or increase the dose during severe exacerbations of bronchial asthma or in cases of significant or sudden worsening of the disease course.

The medicinal product should not be used to relieve acute symptoms of asthma attacks. In case of an acute attack, a short-acting β2-agonist should be used. Patients should be informed about the necessity of seeking immediate medical help in case of sudden asthma exacerbation.

Concomitant conditions

Formoterol should be used with particular caution and under medical supervision, especially regarding adherence to the recommended dosage, in the following conditions: ischemic heart disease, cardiac arrhythmias (particularly third-degree AV block), uncompensated heart failure, idiopathic subaortic stenosis, severe arterial hypertension, aneurysm, pheochromocytoma, hypertrophic obstructive cardiomyopathy, thyrotoxicosis, or other serious cardiovascular disorders such as tachyarrhythmia or severe heart failure. Formoterol may prolong the QTc interval. The medicinal product should be used cautiously in patients taking drugs that affect the QTc interval (see section "Interaction with other medicinal products and other forms of interaction").

Caution should be exercised when administering theophylline and formoterol concomitantly in patients with pre-existing heart disease.

Due to the hyperglycemic effect of β2-stimulants, blood glucose levels should be monitored in patients with diabetes mellitus.

Hypokalemia

β2-adrenergic stimulant therapy may lead to potentially serious hypokalemia. Particular caution is advised in cases of severe asthma, as this effect may be intensified by concomitant therapy and hypoxia (see section "Interaction with other medicinal products and other forms of interaction"). In such situations, serum potassium levels should be checked.

Paradoxical bronchospasm

Like other inhaled medicinal products, formoterol may cause paradoxical bronchospasm; in such a case, the drug should be discontinued and alternative treatment initiated.

Use during pregnancy or breastfeeding.

Pregnancy

Teratogenic effects were not observed in animal studies. In animal studies, formoterol caused implantation loss and reduced survival in the early postnatal period, as well as reduced birth weight. These effects were observed at significantly higher systemic exposure than those achieved with clinical use of formoterol. However, until further experience is available, formoterol is not recommended during pregnancy (especially late pregnancy or labor), except when no alternative treatment is available. Treatment with formoterol may be considered only if necessary for controlling bronchial asthma and if no other safe alternative exists, taking into account that the expected benefit to the mother outweighs the risk to the fetus.

Breastfeeding

The active substance has been detected in the milk of lactating rats, but it is unknown whether formoterol penetrates into human breast milk. For this reason, breastfeeding is recommended to be discontinued if treatment is necessary.

Fertility

Data on the effect of formoterol on human fertility are lacking. In studies in male and female rats, no fertility impairment was observed.

Ability to affect reaction speed when driving or operating machinery.

If dizziness or other similar adverse effects occur during treatment, patients should refrain from driving vehicles or operating complex machinery.

Method of Administration and Dosage

Method of administration – by inhalation.

Formoterol is intended for use in adults, including elderly patients, and children aged 6 years and older.

Adults (including elderly patients and children aged 12 years and older)

Bronchial Asthma

Formoterol should only be used as an add-on to inhaled corticosteroids. Regular maintenance therapy: 1 inhalation (12 mcg) twice daily. In severe disease, this dosage regimen may be increased to 2 inhalations (24 mcg) twice daily. This dosing regimen ensures symptom relief throughout the day. The maximum daily dose is 4 inhalations (48 mcg).

The medicinal product should not be used to relieve acute symptoms of asthma attacks. In case of an acute attack, a short-acting β2-agonist should be used (see section "Special Warnings and Precautions for Use").

Chronic Obstructive Pulmonary Disease (COPD)

Regular maintenance therapy: 1 inhalation (12 mcg) twice daily.

Children aged 6 to 12 years

Bronchial Asthma

Formoterol should only be used as an add-on to inhaled corticosteroids. Regular maintenance therapy: 1 inhalation (12 mcg) twice daily.

The maximum recommended daily dose is 24 mcg.

When prescribing inhaled corticosteroids and long-acting β2-agonists to children aged 6–12 years, a combination product is recommended, except when it is more appropriate to administer the inhaled corticosteroid and long-acting β2-agonist separately.

The medicinal product should not be used to relieve acute symptoms of asthma attacks. In case of an acute attack, a short-acting β2-agonist should be used (see section "Special Warnings and Precautions for Use").

Renal or Hepatic Impairment

There are no theoretical reasons to expect that dose adjustment of formoterol is necessary in patients with renal or hepatic impairment; however, clinical data on use in these patient groups are lacking.

Elderly Patients (aged 65 years and older)

The pharmacokinetics of formoterol have not been studied in elderly populations. Available results from clinical trials involving elderly patients do not indicate the need for doses different from those recommended for other adults.

The duration of action of formoterol is approximately 12 hours. Treatment should always be initiated with the lowest effective dose.

Long-acting β2-agonists may be added to the treatment regimen in patients whose symptoms of bronchial asthma are not adequately controlled with high doses of inhaled corticosteroids. Patients should be warned not to discontinue or alter their corticosteroid therapy when starting treatment with formoterol.

If necessary, one or two additional doses per day may be prescribed for symptom relief in addition to the maintenance dose. However, if increased use becomes necessary more frequently than usual (i.e., more than twice a week), the dose should be reviewed, as this may indicate worsening of the underlying disease.

When switching a patient from another inhaler to Foratec, the treatment regimen should be individually tailored, taking into account previous therapy, dosing regimen, and method of administration.

Warning: The use of more than 4 doses of the drug (48 mcg) per day is prohibited (risk of cardiac arrest).

Instructions for Use of the Inhaler

A physician or other healthcare professional must explain to the patient how to use the inhaler correctly.

Before first use and after an interruption of 3 or more days, one spray should be released into the air to ensure proper functioning of the device. The patient should stand or sit upright when administering the inhalation.

1. Remove the protective cap.
2. Breathe out fully.
3. Hold the inhaler upright with the mouthpiece at the bottom, place the mouthpiece in the mouth, and close lips tightly around it.
4. Inhale deeply through the mouth while simultaneously pressing down on the top of the inhaler to release a spray.
5. Hold breath as long as comfortably possible, then remove the inhaler from the mouth and exhale.
6. If a second inhalation is needed, keep the inhaler in the upright position for half a minute, then repeat steps 2–5.
7. After use, replace the cap on the inhaler.

CAUTION! Do not rush through steps 2–4.

Patients with weak hand strength may find it easier to hold the inhaler with both hands. In this case, place the index fingers on the top of the inhaler and the thumbs on the bottom.

Children

The product is not intended for use in children under 6 years of age.

Overdose

Symptoms: Overdose of formoterol may lead to effects typical of excessive action of other β2-adrenergic stimulants, such as nausea, vomiting, headache, tremor, drowsiness, palpitations, tachycardia, ventricular arrhythmias, metabolic acidosis, hypokalemia, hyperglycemia, QTc interval prolongation, and arterial hypertension.

Treatment: In case of formoterol overdose, treatment should be discontinued immediately, and supportive and symptomatic therapy should be initiated. In severe cases, hospitalization is required.

β-adrenoblockers may be considered, but only with extreme caution, as their use may provoke bronchospasm. Serum potassium levels should be monitored.

Adverse reactions.

The frequency of the adverse reactions listed below is defined as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000) and very rare (<1/10000).

* The percentage of patients with serious exacerbations of bronchial asthma participating in clinical trials was higher in the group receiving formoterol than in the placebo group, with the greatest difference observed in children aged 5–12 years.

** These adverse reactions were reported by patients treated with the medicinal product containing formoterol during the post-marketing period.

As with all other types of inhaled therapy, paradoxical bronchospasm may occur very rarely (see section "Special precautions for use"). Treatment with β2-agonists may cause increased blood levels of insulin, free fatty acids, glycerol, and ketone bodies.

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions after registration of the medicinal product is important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Information System for Pharmacovigilance at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 30 °C in the original packaging.

Do not freeze.

Keep out of reach of children.

Packaging.

120 doses per aluminum container. One aluminum container with metering valve, plastic spray device, and protective cap in a cardboard box.

Prescription category. Prescription only.

Manufacturer.

Cipla Ltd. (Unit II)

Manufacturer's address and location of its operations.

Plots No. L-139, S-103 and M-62, Verna Industrial Estate, IN–403 722 Verna, Goa, India.