Formoterol

Pharmacological properties

formoterol fumarate is a selective β2-adrenergic receptor agonist. in patients with reversible obstruction of the airways it has a quick bronchodilating effect (for 1-3 minutes), which persists for 12 hours after inhalation at a high level. in therapeutic doses, the effect on the cardiovascular system is minimal and occurs only in individual cases.

Formoterol inhibits the release of histamine and leukotrienes from a passively sensitized human lung. Some anti-inflammatory effect was noted, such as a decrease in the severity of edema and inflammatory cell accumulation.

Pharmacokinetics As with other drugs for inhalation, about 90% of formoterol, when used with an inhaler, is swallowed and absorbed in the digestive tract. Therefore, the pharmacokinetic characteristics of formoterol for oral administration can be largely applied to powder for inhalation.

Oral doses of formoterol fumarate up to 300 mcg are rapidly absorbed in the digestive tract. C_max an unchanged substance in the blood plasma is reached after 0.5–1 hours. The degree of absorption of 80 μg of the drug taken orally is ≥65%.

The pharmacokinetics of formoterol are linear within the studied doses of 20–300 μg orally. Repeated administration of an oral daily dose of 40–160 μg does not lead to significant accumulation of the drug in the body. After inhaled administration in therapeutic doses, formoterol cannot be determined in blood plasma using currently available analytical methods. However, urinary excretion rates indicate rapid absorption after inhalation. The maximum rate of excretion after administration at a dose of 12–96 mcg in most cases was achieved after 1-2 hours.

The cumulative excretion of formoterol in the urine after inhalation of the powder (12–24 μg) and two aerosol preparations (12–96 μg) proves that the amount of formoterol in the blood plasma increases in proportion to the dose taken.

Binding to blood plasma proteins is 61–64% (of which 34% is albumin), therefore, at the concentrations achieved when taken in therapeutic doses, saturation of the binding sites does not occur.

Formoterol is excreted by metabolism, mainly by direct glucuronidation of the molecule. Another route of excretion is O-demethylation followed by glucuronidation.

Formoterol can be excreted in several stages, the actual T_½ depends on the interval between receptions. Given the plasma concentration at 6, 8, or 12 hours after oral administration, T was determined_½2–3 hours T_½established by the rate of excretion in urine 3–16 hours after inhalation was about 5 hours.

The active substance and metabolites are completely excreted from the body; about ²/₃ the oral dose was detected in urine and ¹/₃ - in the feces. After inhalation, on average, about 6–9% of the dose was excreted unchanged in the urine.

The renal clearance of formoterol is 150 ml / min.

Indications

Prevention and treatment of bronchoconstriction in patients with reversible bronchial obstruction, BA and chronic bronchitis, with or without emphysema.

Prevention of bronchospasm caused by inhalation of allergens, cold air or physical activity.

Application

Fortix is ​​intended for adults, including elderly patients, and children over the age of 6 years.

Since the bronchodilating effect of formoterol is largely preserved after 12 hours, in most cases, supportive treatment with two inhalations per day makes it possible to control bronchoconstriction associated with chronic conditions both day and night.

Maintenance therapy

Adults and children over 6 years: 1 capsule for inhalation (12 mcg) 2 times a day. In severe cases, 2 capsules can be prescribed 2 times a day.If necessary, to reduce the severity of symptoms, in addition to the maintenance dose, 1 or 2 capsules per day can be used. However, if the use of the drug in high doses is necessary more often than usual (that is, more often than 2 times a week), the dose must be reviewed, as this may indicate a worsening of the underlying disease.

Prevention of bronchospasm caused by physical exertion or the influence of known allergens, which cannot be avoided

Adults: 1 capsule for inhalation (12 mcg) approximately 15 minutes before exercise or contact with an allergen. Patients with severe AD may need 2 capsules for inhalation (24 mcg).

Children aged 6 years: 1 capsule for inhalation (12 mcg) approximately 15 minutes before exercise or contact with an allergen.

Application

The doctor or other healthcare provider must explain to the patient how to use the inhaler.

Capsules are removed from the blister just before use.

1. Remove the protective cap.

2. To open the inhaler, it is necessary to grasp its base and turn the mouthpiece counterclockwise.

3. Place the capsule in the chamber at the base of the inhaler. It is important to remove the capsule from the blister pack just before use.

4. Return the mouthpiece to the closed position.

5. Press the red buttons while holding the inhaler upright. Release the buttons.

6. Exhale completely.

7. Place the mouthpiece in your mouth and tilt your head back slightly. Clamp the mouthpiece with your lips and inhale quickly and continuously as deeply as possible.

8. Hold your breath for as long as possible without causing discomfort while simultaneously removing the inhaler from your mouth. Then exhale. Open the inhaler to check if the powder remains in the capsule. If left, repeat steps 6–8.

9. After use, remove the empty capsule, close the mouthpiece and close the inhaler with a cap again.

To remove powder residues, clean the mouthpiece and capsule chamber with a dry cloth, you can also use a soft brush to clean.

Contraindications

Hypersensitivity to formoterol, other components of the drug or other β2-adrenergic agonists.

Tachyarrhythmia, atrioventricular block of the 3rd degree, idiopathic subvalvular aortic stenosis, hypertrophic obstructive cardiomyopathy, thyrotoxicosis.

Patients with suspected or established prolongation of the QT interval (QT_c 0.44 s).

Children under 6 years old.

Side effects

From the musculoskeletal system: tremor, muscle spasms, myalgia.

From the cardiovascular system: increased heart rate, tachycardia.

From the nervous system: headache, agitation, dizziness, anxiety, nervousness, insomnia, a feeling of anxiety.

From the respiratory system: worsening of the clinical condition, dry mouth.

Others: irritation of the mucous membrane of the mouth and throat.

Special cases: hypersensitivity reactions, such as severe arterial hypotension, rashes, angioedema, itching, peripheral edema, a change in taste, nausea, irritation of the mucous membrane of the eyes, swelling of the eyelids.

special instructions

The drug should not be used in patients with hereditary galactose intolerance, lack of lactase in the paw, or impaired absorption of glucose or galactose.

Agonists β₂long-acting adrenoreceptors are not intended (and insufficient) for basic treatment of AD. Along with regular treatment with β agonists₂-adrenoreceptors in patients with AD it is necessary to use regular concomitant treatment with inhaled anti-inflammatory drugs (for example, corticosteroids and / or sodium cromoglycate in children) or oral corticosteroids.Before prescribing formoterol, the patients condition should be assessed to determine whether he is receiving sufficient anti-inflammatory treatment. When control over the symptoms of AD is achieved, a gradual reduction in the dose of formoterol is necessary. During a dose reduction period, the patients condition should be regularly monitored. It is necessary to apply the lowest effective dose of formoterol.

Although formoterol can be included in the treatment regimen if inhaled corticosteroids do not provide sufficient control over the symptoms of asthma, treatment with formoterol should not be started during a severe exacerbation of asthma or in the case of a significant or acute deterioration in its course.

At the beginning of treatment with formoterol, there is a risk of developing side effects associated with AD, as well as a deterioration in its course. If AD symptoms remain uncontrollable or if the patient becomes worse after inhalation of formoterol, it is necessary to consult a doctor regarding the advisability of continuing treatment.

The anti-inflammatory treatment should not be canceled after the initiation of formoterol therapy, even if the severity of the symptoms of the disease decreases. The persistence of symptoms or the need to increase the dose of formoterol to control them usually indicates a worsening of the underlying disease and the need for treatment correction.

Fatalities have been reported with excessive use of drugs containing β agonists₂-adrenoreceptors, although the exact cause of death is unknown. In several cases, the cause of death was cardiac arrest. Patients should be warned about the importance of strict adherence to dosing recommendations and the inadmissibility of exceeding the maximum dose.

When using β agonists₂-adrenergic receptors at doses higher than recommended noted prolongation of the QT interval on the ECG, which increased the risk of changes in ventricular rhythm.

The dosage limits for patients using formoterol should be carefully evaluated in such cases:

- coronary heart disease;

- myocardial infarction;

- severe hypertension;

- Heart arythmy;

- severe heart failure.

Treatment with β agonists₂β-adrenergic receptors can cause potentially severe hypokalemia. Particular caution is necessary in severe AD, since this effect may be enhanced by concomitant treatment and hypoxia. In this case, it is necessary to control the level of potassium in the blood plasma.

As for other inhaled drugs, it is necessary to consider the possibility of paradoxical bronchospasm; in this case, the drug should be discontinued and alternative treatment prescribed.

Due to the hyperglycemic action of β agonists₂-adrenoreceptors it is necessary to control the level of glucose in the blood of patients with diabetes mellitus.

Children. Formoterol is not used in children under the age of 6 years.

During pregnancy and breastfeeding. The safety of the use of formoterol during pregnancy and lactation has not been established. The drug should not be used during pregnancy only if there is no other safe alternative. Like other β agonists₂-adrenoreceptors, formoterol can delay labor due to the relaxing effect on the smooth muscles of the uterus.

It is not known whether formoterol passes into breast milk. Therefore, in each case, it is necessary to carefully assess the benefits and risks.

The ability to influence the reaction rate when driving vehicles and working with other mechanisms. The patient must be warned about the likelihood of impaired ability to drive vehicles and complex mechanisms due to the development of side effects such as tremors or agitation.

Interactions

The use of drugs such as quinidine, disopyramide, procainamide, phenothiazine, antihistamines, and tricyclic antidepressants may be associated with a prolonged q – t interval and an increased risk of ventricular arrhythmia.

The additional use of sympathomimetic drugs can increase the severity of reactions from the cardiovascular system.

Formoterol should be used with caution in patients using MAO inhibitors or tricyclic antidepressants, since they can enhance the action of β agonists₂-adrenoreceptors to the cardiovascular system.

Concomitant treatment with xanthine derivatives, steroids or diuretics may enhance the possible hypokalemic effect of β₂-agonists. Hypokalemia may increase the tendency to cardiac arrhythmias in patients taking digitalis preparations. Β-adrenergic blockers can weaken or neutralize the effect of formoterol, so β-adrenoreceptor blockers (including eye drops) cannot be used simultaneously with formoterol, unless there is an alternative.

Overdose

Symptoms: nausea, vomiting, headache, tremor, dizziness, palpitations, tachycardia, ventricular arrhythmia, metabolic acidosis, hypokalemia, hyperglycemia.

In case of overdose of formoterol, treatment should be stopped immediately and supportive and symptomatic therapy should be started. In case of severe overdose, the patient must be hospitalized.

Storage conditions

In the original packaging at temperatures up to 25 ° C.