Pharmacological action Foradil Aerolizer
Selective β2-adrenoceptor agonist. It has a bronchodilator effect in patients with both reversible and irreversible and airway obstruction. Effect of the drug occurs rapidly (within 1-3 min) and stored for 12 hours after inhalation. When using the drug at therapeutic doses, effects on the cardiovascular system is minimal and occurs only in rare cases.
Foradil inhibits the release of histamine and leukotrienes from mast cells. In animal experiments were shown some anti-inflammatory properties of formoterol, such as the ability to inhibit the development of edema and accumulation of inflammatory cells.
In experimental animal studies in vitro have shown that racemic formoterol and its (R, R) – and (S, S)-enantiomers are highly selective agonists of β2-receptors. (S, S)-enantiomer was 800-1000 times less potent than (R, R)-enantiomer, and had no negative impact on the activity of (R, R)-enantiomer with respect to effects on tracheal smooth muscle. There was no evidence obtained by pharmacological advantages of using one of the two enantiomers in comparison with the racemic mixture.
In studies in humans have shown that Foradil effectively prevents bronchospasm caused by inhaled allergens, exercise, cold air, histamine or methacholine. Since the bronchodilatory effect Foradila is expressed in the 12 hours after inhalation, maintenance therapy, where prescribed Foradil 2 times / day, which in most cases provide the necessary control of bronchospasm in chronic lung diseases, both during the day and night.
In patients with chronic obstructive pulmonary disease (COPD), a stable flow of formoterol used by inhalation through the device Aerolizer at doses of 12 mg or 24 mg 2 times / day, causes a rapid onset of bronchodilatory effect, which lasts for a minimum of 12 hours and is accompanied by subjective improvement in terms of the parameters of quality of life.
Pharmacokinetics Foradil Aerolizer
The therapeutic dose range is between formoterol 12 mcg to 24 mg 2 times / day. The data on the pharmacokinetics of formoterol were obtained from healthy volunteers after inhalation of formoterol at doses above the recommended range and in COPD patients after inhalation of formoterol at therapeutic doses.
Absorption
After a single inhalation of formoterol fumarate at a dose of 120 mcg formoterol in healthy volunteers rapidly absorbed into plasma, Cmax of formoterol in plasma was 266 pmol / L and was achieved within 5 min after inhalation. COPD patients treated with formoterol in a dose of 12 or 24 mg 2 times / day for 12 weeks, the concentrations of formoterol in plasma measured after 10 min, 2 h and 6 h after inhalation, were in the range 11.5-25.7 pmol / L and 23.3 -50.3 pmol, respectively.
In studies that examined the total excretion of formoterol and its (R, R) – and (S, S)-enantiomer in the urine, it was shown that the amount of formoterol in the systemic circulation is increased proportional to the inhaled dose (12-96 mg).
After inhalation of formoterol in a dose of 12 or 24 mg 2 times / day for 12 weeks, excretion of unchanged formoterol in urine of patients with asthma increased by 63-73%, and in patients with COPD – by 19-38%. This indicates some cumulation of formoterol in plasma after repeated inhalation. It is not mentioned much cumulation of one of the enantiomers of formoterol compared with the other after repeated inhalation.
Also, as reported for other drugs used in inhalation, most of formoterol, used with an inhaler will be swallowed and then absorbed from the gastrointestinal tract. In the appointment of 80 ug of 3H-labeled formoterol into two healthy volunteers was absorbed at least 65% of formoterol.
Distribution
The binding of formoterol to plasma proteins is 61-64% (in the first place, by binding to albumin – 34%).
In the range of concentrations observed after the drug at therapeutic doses, saturation of binding sites is not achieved.
Metabolism
The main route of metabolism of formoterol is direct glucuronidation. Another metabolic pathway – the o-demethylation followed by glucuronidation.
Irrelevant pathways include conjugation of formoterol sulfate followed deformilirovaniem. The set of isoenzymes involved in the process of glucuronidation (UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A9, 1A10, 2B7 and 2B15) and 0-demethylation (CYP2D6, 2C19, 2C9, 2A6) of formoterol that predpolagaget a low probability of drug interactions through inhibition of isoenzyme or taking part in the metabolism of formoterol. At therapeutic concentrations, formoterol did not inhibit isozymes of cytochrome P450.
Breeding
In patients with asthma and COPD, formoterol fumarate treated at a dose of 12 or 24 mg 2 times daily for 12 weeks, approximately 10% or 7%, respectively, determined in the urine as unchanged formoterol. The calculated proportion of (R, R) – and (S, S)-enantiomers of unchanged formoterol in urine accounted for 40% and 60% respectively after a single dose of formoterol (12-120 mg) in healthy volunteers after single and repeated doses of formoterol in patients with bronchial with asthma.
The active substance and its metabolites are completely eliminated from the body, about two thirds of the applicable oral dose is excreted in the urine, with the third – in the feces. Renal clearance of formoterol is 150 mL / min.
In healthy volunteers, the end of T1 / 2 of formoterol from plasma after a single inhaled dose of 120 mg of 10 h, end of T1 / 2 (R, R) – and (S, S)-enantiomers, calculated from urinary excretion accounted for 13.9 and 12.3 respectively.
Pharmacokinetics in special clinical situations
Pharmacokinetic parameters of formoterol in both men and women do not have significant differences.
The pharmacokinetics of formoterol in elderly patients has not been studied.
In a clinical study in children aged 5-12 years with bronchial asthma treated with formoterol fumarate at a dose of 12 or 24 mg 2 times / day for 12 weeks, excretion of unchanged formoterol excretion was increased by 18-84% compared with the corresponding indicator measured after the first dose.
In clinical studies in children in the urine was determined by about 6% of unchanged formoterol.
The pharmacokinetics of formoterol in patients with impaired liver function and / or kidney disease has not been studied.
Statement Foradil Aerolizer
- Prevention and treatment of bronchospasm in patients with bronchial asthma;
- Prevention of bronchospasm induced by inhaled allergens, cold air or physical exercise;
- Prevention and treatment of disorders of bronchial patency in patients with chronic obstructive pulmonary disease (COPD) in the presence of both reversible and irreversible because of bronchial obstruction, chronic bronchitis and emphysema.
Dosage and administration Foradil Aerolizer
Foradil is for inhalation use in adults and children age 5 and older. The drug is a powder for inhalation, used with a special device – Aerolizer, which is included in the package.
For adults with asthma, the dose for regular maintenance therapy is 12-24 mg (contents of 1-2 capsules) 2 times / day. If necessary, you can apply an additional 12-24 mg / day. If you need to use extra doses of the drug ceases to be episodic (for example, becomes more than 2 days per week), you should consult a physician for review of treatment, as this may indicate a worsening of underlying disease.
In order to prevent bronchospasm caused by exercise or unavoidable exposure known allergen for 15 minutes before the alleged contact with the allergen load or to be inhaled the contents of one capsule (12 micrograms). Patients with asthma may need a heavy flow of a single dose of 24 micrograms.
Chronic obstructive pulmonary disease dose for regular maintenance therapy is 12-24 mg (contents of 1-2 capsules) 2 times / day.
For children aged 5 years and older with asthma, the dose for regular maintenance therapy is 12 mg 2 times / day.
In order to prevent bronchospasm caused by exercise or unavoidable exposure known allergen for 15 minutes before the alleged contact with the allergen load or to be inhaled the contents of one capsule (12 micrograms).
Rules of the inhalation
In order to ensure the correct use of the drug, the patient should be instructed by a doctor or other health professional about the rules of the inhalation. We need to show the patient how to use an inhaler, to explain to the patient that use capsules with powder for inhalation should be only through Aerolizer, warn the patient that the capsules are intended for inhalation use only and not intended for ingestion.
It is important that patients understand that due to the destruction of small pieces of gelatin capsule of gelatin as a result of inhalation may fall into the mouth or throat. In order to reduce this phenomenon to a minimum, you should not pierce the capsule more than 1 times.
Remove the capsule from the blister package until immediately before use.
Instructions for use Aerolizer
1. Remove the cap from Aerolizer.
2. Aerolizer grip the base and turn mouthpiece in the direction of the arrow.
3. Place the capsule in the cell that appears at the bottom Aerolizer (it takes the form of capsules). Keep in mind that removing the capsule from the blister pack immediately prior to inhalation.
4. Turning the mouthpiece close Aerolizer.
5. Holding Aerolizer in strictly vertical position once pressure until the end of the blue buttons available on either side Aerolizer. Then let them go.
At this stage, piercing the capsule, it may be destroyed, so that small pieces of gelatin might reach the mouth or throat. Since gelatin is edible, it does not cause any harm. In order to complete capsule is destroyed, you must meet the following requirements: Do not puncture the capsule more than once to observe the rules of storage, remove the capsule from the blister until just prior to inhalation.
6. Make a full breath.
7. Take the mouthpiece in your mouth and gently tilt the head back. Wrap your lips and the mouthpiece to make a quick, even, as a deep breath. If the patient needs to hear the characteristic rattling sound produced by the rotation of the capsule and spray powder. If the characteristic sound was not, then you need to open Aerolizer and see what happened to the capsule. Maybe it got stuck in the cell. In this case, you must carefully remove the capsule. In no case do not try to release the capsule by repeated taps on the buttons on the sides Aerolizer.
8. If inhalation hear a distinctive sound, you should hold your breath as long as possible. At the same time remove the mouthpiece from the mouth. Then make an exhalation. Open Aerolizer and see if there was a capsule of powder. If the capsule remained in the powder, re-do the steps described in paragraphs 6-8.
9. After the procedure to open Aerolizer inhalation, remove the empty capsule, close mouthpiece and close Aerolizer cap.
For the removal of the powder should be wiped with a mouthpiece and a cell with a dry cloth. You can also use a soft brush.
Side effect Foradil Aerolizer
Adverse reactions are distributed in accordance with the frequency of occurrence. To estimate the frequency of the following criteria: very common (≥ 10%), common (≥ 1% <10%), sometimes (≥ 0.1%, <1%), rarely (≥ 0.01%, <0.1%); very rare (<0.01%), including isolated reports.
By the immune system: very rarely – hypersensitivity reactions such as hypotension, urticaria, angioedema, pruritus, rash.
The nervous system and psyche often – headache, tremor, and sometimes – agitation, anxiety, nervousness, insomnia, dizziness, irritability, and very rarely – a violation of taste.
Cardio-vascular system: often – palpitations, and sometimes – tachycardia is very rare – peripheral edema.
The respiratory system: sometimes – bronchospasm.
Local reactions: sometimes – irritation of the mucous membrane of the pharynx and larynx.
Part of the digestive system: very rarely – nausea.
On the part of the musculoskeletal system: sometimes – muscle cramps, myalgia.
Contraindications Foradil Aerolizer
- Children up to age 5 years;
- Lactation (breastfeeding);
- Hypersensitivity to the drug.
Pregnancy and breast feeding
Safety of Foradil during pregnancy and lactation has not yet been established.
Use of the drug during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus. Formoterol, as well as other beta2-agonists may slow down the process of birth due to tocolytic action (relaxing effect on smooth muscle of the uterus).
Is not known whether formoterol in human breast milk. Mothers taking Foradil should not breast-feed.
Cautions
Take special care when applying Foradil (especially in terms of dose reduction) and careful monitoring of patients is required under the following comorbid conditions: coronary heart disease, irregular heart rhythm and conduction, particularly AV-block III degrees, severe heart failure, idiopathic podklapanny aortic stenosis; hypertrophic obstructive cardiomyopathy, thyrotoxicosis, known or suspected prolongation QTc (QT ARR)> 0.44 sec.
Due to the hyperglycemic effect, characteristic of beta 2-agonists in patients with diabetes should take extra regular monitoring of blood glucose.
Typically, patients with asthma who require therapy beta2-agonists should also regularly receive adequate doses of protivoovspalitelnyh means (eg, corticosteroids for inhalation or ingestion, and / or children – sodium cromoglycate). In the appointment of the drug to patients not receiving anti-inflammatory therapy, it should be started simultaneously with Foradil. In appointing Foradil need to assess the condition of patients with respect to the adequacy of the anti-inflammatory therapy they receive. After starting treatment, patients should Foradilom continue to recommend anti-inflammatory therapy unchanged, even if it is marked improvement.
Necessary to revise the basic medical treatment of bronchial asthma in the case against the use of stored Foradil asthma symptoms, or if the number of doses Foradil required to control symptoms of the disease increases, as it usually indicates a worsening of the disease.
Consequence of therapy beta2-agonists may be the development of a potentially serious hypokalemia. Since the the action of the drug may be enhanced by hypoxia and concomitant treatment, special caution should be exercised in patients with bronchial asthma, severe course. In these cases, we recommend regular monitoring of serum potassium levels.
As well as during other inhalation therapy, you should consider the possibility of paradoxical bronchospasm. If it occurs, immediately remove the drug and to appoint an alternative treatment.
Effects on ability to drive and control mechanisms
Patients who during treatment occurs Foradila dizziness or other disorders of the central nervous system, they should refrain from driving a vehicle or control mechanisms during treatment.
Overdose Foradil Aerolizer
Symptoms: Foradila overdose can be expected to lead to the phenomena characteristic of the excess of the other beta2-agonists, such as nausea, vomiting, headache, tremor, drowsiness, palpitations, tachycardia, ventricular arrhythmias, metabolic acidosis, hypokalemia, hyperglycemia.
Treatment: shown holding a supportive and symptomatic therapy. In severe cases require hospitalization.
Can be considered beta-blockers, but only subject to extreme caution, because use of such equipment may cause bronchospasm.
Drug Interactions Foradil Aerolizer
Foradil (like other beta2-adrenostimulyatory) should be used with caution in patients receiving such drugs as quinidine, disopyramide, procainamide, phenothiazines, antihistamines, MAO inhibitors, tricyclic antidepressants and other drugs, which are known to prolong interval QT, because in these cases, the effect of agonists on the cardiovascular system may be enhanced. When using drugs that can lengthen the interval QT, and increased risk of ventricular arrhythmias.
The simultaneous use of other sympathomimetic agents can lead to aggravation of side effects Foradil.
The simultaneous use of xanthine derivatives, corticosteroids or diuretics may increase the potential effect of beta2-gipokaliemicheskoe agonists. Hypokalemia may increase susceptibility to the development of cardiac arrhythmias in patients receiving digitalis preparations.
Beta-blockers may reduce the effect Foradil. In this regard, you should not use Foradil with beta-blockers (including eye drops), if only to use a combination of drugs does not compel any extraordinary reasons.
