Formoterol
When ATH:
R03AC13
Characteristics formoterol
Available in the form of formoterol fumarate dihydrate and formoterol fumarate. Formoterola fumarate is a white or yellowish crystalline powder. Easily soluble in glacial acetic acid, Soluble in methanol, to a lesser extent - in ethanol and isopropanol, slightly soluble in water, practically insoluble in acetone, ethyl acetate and diethyl ether.
Mode of action of formoterol
Adrenomimeticheskoe, bronchodilatory.
The use of formoterol
According to the Physician Desk Reference (2003), Formoterol fumarate is indicated for the long-term (twice a day - morning and evening) maintenance treatment of asthma and the prevention of (in adults and children 5 and older) bronchospasm in reversible obstructive airway diseases, incl. in patients with symptoms of nocturnal asthma, which needs regular inhaled short-beta2-adrenomimetikov.
It can be used in asthma together with short beta2-agonistami, kortikosteroidami (systemic administration or inhalation) and theophylline.
The use of formoterol fumarate "on demand" (if necessary) It shows for adults and children 12 and older for rapid alert bronchospasm, exercise-induced.
Formoterol fumarate is used in patients with COPD, including chronic bronchitis and emphysema, for long-term maintenance therapy.
Contraindications formoterol
Hypersensitivity.
Limitations to the use of formoterol
Cardiovascular disorders, incl. coronary insufficiency, Arrhythmia, arterial hypertension, convulsive disorders, thyrotoxicosis, unusual response to sympathomimetic, pregnancy, breast-feeding, Age to 5 years (Safety and efficacy have not been established).
Formoterol fumarate is not recommended for patients, who manage to control asthma but not systematic beta agonists, inhaled short-2-adrenoreceptorov.
Pregnancy and breast-feeding
Adequate controlled studies of formoterol fumarate in pregnant women, incl. during childbirth, not performed. Formoterol fumarate should be used during pregnancy and childbirth (as beta-agonists may have a negative effect on uterine contractility) only in those cases, when the intended benefits to the mother outweighs the potential risk to the fetus. Formoterol fumarate is excreted in the milk of rats. Unknown, whether it is excreted in breast milk in women, but since many drugs are excreted in human milk, formoterol fumarate should be used with caution in nursing mothers (well-controlled studies in lactating women have not been conducted).
Side effects of formoterol
Side effects of formoterol fumarate side effects are similar to other selective beta2-agonists and include angina, arterïalnwyu hypo- or hypertension, taxikardiju, aritmiju, nervousness, Headache, tremor, dry mouth, heartbeat, dizziness, convulsions, nausea, fatiguability, weakness, hypokalemia, giperglikemiû, metabolic acidosis and insomnia.
Bronchial asthma
During controlled clinical trials of formoterol fumarate (by 12 g 2 once a day) received 1985 patients (children 5 and older, adolescents and adults) asthmatic. Among the side effects identified with the frequency of formoterol fumarate 1% and more, than the frequency of adverse events in the placebo group, We note the following (next to the percentage of occurrence of this side effect in the group of formoterol fumarate, in parentheses in the placebo group):
From the nervous system and sensory organs: tremor 1,9% (0,4%), dizziness 1,6% (1,5%), insomnia 1,5% (0,8%).
From the respiratory system: bronchitis 4,6% (4,3%), chest infection 2,7% (0,4%), dyspnoea 2,1% (1,7%), tonsillitis 1,2% (0,7%), disfonija 1,0% (0,9%).
Other: viral infections 17,2% (17,1%), chest pain 1,9% (1,3%), rash 1,1% (0,7%).
Three side-effects - tremors, dizziness and dysphonia - were dose-dependent (studied dose 6, 12 and 24 mcg when receiving twice a day).
Safety of formoterol fumarate compared to placebo was investigated in a multicentre, randomized,, double-blind clinical trial in 518 children aged 5-12 years, asthmatic, require daily reception of bronchodilators and anti-inflammatory drugs. While taking on 12 mcg formoterol fumarate 2 twice daily incidence of adverse events was comparable to that in the placebo group. The nature of adverse events, detected in children, different from the side effects of formoterol fumarate, marked in adults. Side effects in the group of formoterol fumarate in children, Larger than the detection rate of side effects in the placebo group, include infection / inflammation (viral infections, rhinitis, tonsillitis, gastroenteritis) or complaints from the gastrointestinal tract (abdominal pain, nausea, dyspepsia).
COPD
In two controlled studies of formoterol fumarate (by 12 g 2 once a day) received 405 COPD patients. The frequency of adverse events was comparable in groups of formoterol fumarate and placebo. Among the side effects in a group with a frequency of formoterol fumarate, equal to or greater than 1% and superior to the placebo group, We note the following (next to the percentage of occurrence in the group of formoterol fumarate, in parentheses in the placebo group):
From the nervous system and sensory organs: convulsions 1,7% (0%), leg cramps 1,7% (0,5%), anxiety 1,5% (1,2%).
From the respiratory system: upper respiratory tract infection 7,4% (5,7%), pharyngitis 3,5% (2,4%), sinusitis 2,7% (1,7%), increase in the number of sputum 1,5% (1,2%).
Other: backache 4,2% (4,0%), chest pain 3,2% (2,1%), fever 2,2% (1,4%), itch 1,5% (1,0%), dry mouth 1,2% (1,0%), injury 1,2% (0%).
Generally, frequency of all cases of cardiovascular side effects in two main research was low and comparable to placebo (6,4% patients, Take on 12 ug of formoterol fumarate twice a day, and 6,0% placebo). Specific cardiovascular side effects in a group of formoterol fumarate, occurs with a frequency 1% or more greater than the incidence in the placebo group, There were no.
In two studies in patients, Take on 12 mcg and 24 ug of formoterol fumarate twice a day, Seven marked dose-dependent side effects (pharyngitis, fever, convulsions, increase in the number of sputum, disfonija, myalgia and tremor).
Post-marketing studies
In the wide post-marketing use of formoterol fumarate was reported severe exacerbations of asthma, some of which ended fatally. While most of these cases was observed in patients with severe asthma or acute decompensation which developed, several cases were observed in patients with less severe asthma. Communication with the reception of these cases formoterol fumarate has not been determined. There are rare reports of anaphylactic reactions, including severe hypotension and angioedema, associated with inhaled formoterol fumarate. Allergic reactions can manifest as urticaria and bronchospasm. Evidence of drug dependence in the application of formoterol fumarate in clinical trials has been received.
Interaction of formoterol
Other adrenergic agents in patients receiving formoterol should be used with caution, because there is a risk of potentiation of sympathomimetic effects of formoterol predictable. At the same time taking xanthine derivatives, steroids or diuretics may be increased gipokaliemichesky adrenergic receptor agonist effect. ECG changes and / or hypokalemia, due nekaliysberegayuschimi diuretics, such as loop or thiazide diuretics, can suddenly worsen beta-agonists, especially in overdose last (despite the fact that the clinical relevance of these effects is unclear, It requires careful while prescribing these groups). Formoterol, Like other beta2-agonistы, with special attention must be administered while taking MAO inhibitors, tricyclic antidepressants or other drugs, can prolong the QTc interval, as it can potentiate the effect of agonists on the cardiovascular system (increased risk of ventricular arrhythmias). Formoterol and beta-blockers can mutually inhibit the effects of each other while the appointment. Beta-blockers may not only interfere with the pharmacological action of beta-agonists, but also can cause severe bronchospasm in patients with asthma.
An overdose of formoterol
Symptoms: angina, arterial hyper- or hypotension, tachycardia (more 200 u. / min), arrhythmia, nervousness, headache, tremor, seizures, muscle cramps, dry mouth, heartbeat, nausea, dizziness, fatiguability, weakness, kaliopenia, giperglikemiâ, insomnia, metabolic acidosis. Possible heart failure and death (As with all inhaled sympathomimetic). The minimum lethal dose in rats, receiving formoterol fumarate inhalation, made 156 mg / kg (about 53000 and 25000 Inhaled MRDCH times higher for adults and children, respectively, in calculating the body surface area in mg / m2).
Treatment: Cancel formoterol fumarate, symptomatic and supportive therapy, ECG monitoring. Use of cardioselective beta-blockers should be carried out taking into account the potential risk of bronchospasm. Evidence for the effectiveness of dialysis in overdose of formoterol fumarate insufficient.
Dosing and dose of formoterol
Inhalation. Bronchial asthma (maintenance therapy): adults and children 5 and older - for 12 mcg every 12 no. If asthma symptoms occurred in the period between inhalations, should use beta2-agonists of short action. Prevention of asthma attacks, caused by physical activity: Adults and adolescents 12 and older - for 12 micrograms per 15 minutes before the expected load. Repeated administration may not be earlier than 12 hours after the last inhalation. COPD (maintenance therapy): by 12 mcg every 12 no. The maximum recommended dose 24 mg / day.
Precautions
Formoterol fumarate is not intended for acute asthma. If the intake of formoterol fumarate in effective dosage earlier began to arise bronchial asthma or patient is required more, than usual, the number of inhaled beta2-short-acting agonists, one should immediately consult a doctor, as it is often a sign of destabilization of the state. In this case, therapy should be reviewed and additional treatments are assigned (anti-inflammatory therapy, such as corticosteroids); increase in the daily dose of formoterol fumarate thus unacceptable. should not increase the frequency of inhalation (more 2 once a day). Do not use formoterol fumarate in patients with a visible deterioration or decompensation of acute asthma, because it can be life-threatening situation.
In the appointment of formoterol fumarate to patients, previously treated with beta2-adrainomimetiki short acting as a basic therapy (eg, 4 once a day), Patients should be warned of the termination of regular intake of these drugs and their use only as symptomatic therapy in exacerbations of asthma symptoms. As with other inhaled beta2-adrenomimetiki, Formoterol fumarate can cause paradoxical bronchospasm; In this case, receiving formoterol fumarate should be immediately discontinued, and assigned to an alternative treatment. In many patients, monotherapy with beta2-agonists does not provide adequate control of asthma symptoms; such patients require early administration of anti-inflammatory agents, such as corticosteroids.
Had obtained no evidence of clinically significant anti-inflammatory activity of formoterol fumarate, Consequently, it can not be considered as an alternative to corticosteroids. Formoterol fumarate is not intended to substitute for corticosteroids, taken by inhalation or oral; discontinue reception or decrease the dose of corticosteroids should not be. Treatment with corticosteroids in patients, before taking these medications by mouth or inhalation, It should be continued, even if the well-being of patients as a result of receiving formoterol fumarate improved. Any changes in corticosteroid dose, in particular reduction, We should be based only on data from clinical evaluation of the patient's condition.
Like other beta agonists2-adrenoreceptorov, formoterol fumarate, some patients can cause clinically significant cardiovascular effects (increased heart rate, increased blood pressure, and others.); in such cases the receiving formoterol fumarate should be discontinued. Similar to other beta2-adrenomimetikam, formoterol may cause clinically significant hypokalemia (perhaps, due to the redistribution of intracellular ions), which promotes the development of adverse cardiovascular effects. Lowering the level of serum potassium is usually transient in nature and does not require replenishment.
In patients with asthma use of beta-blockers, incl. for secondary prevention of myocardial infarction, undesirable. In such cases, should consider the appointment of cardioselective beta-blockers, although they should be administered with caution.
Cautions
Capsules, soderzhashtie formoterol fumarate, taking into prohibited; they should only be used by inhalation through a special device. should not exercise exhale into the device for inhalation.
