Zafiron time. for ing. in kaps. 12 mkg No. 120 + inhaler

Pharmacological properties

Pharmacodynamics. the formoterola fumarates — selection agonist β2-адренорецепторов. has bronchodilatory effect at patients with reversible obstruction of airways. medicine works quickly (the beginning of action — within 1–3 min.), the effect remains for 12 h after inhalation. at use of medicine in therapeutic doses the influence on a cardiovascular system minimum, it is noted only in some cases.

Formoterol slows down release of a histamine and leukotrienes from passively sensibilized lungs of the person; effectively the bronchospasm caused by allergens, physical activity, cold air, a histamine or metasincaline warns. As the bronchodilatory effect of medicine is expressed for 12 h after inhalation, maintenance therapy at which formoterol appoint 2 times a day allows to provide in most cases necessary control of a bronchospasm at chronic diseases of lungs both in the afternoon, and at night.

Pharmacokinetics. The therapeutic dose of the medicine Zafiron makes 12–24 mkg 2 times a day. The data concerning pharmacokinetic properties of a formoterol are received from researches with the assistance of healthy volunteers after inhalation of the doses exceeding therapeutic and at sick HOBL is after inhalation of therapeutic doses. The quantity of a formoterol excreted with urine in not changed look is used as the mediated indicator of the general influence of medicine on an organism and correlates with data on removal of medicine from blood plasma. T _½ for urine and blood plasma similar.

Absorption. At application of a formoterol in the dose exceeding therapeutic (a single dose — 120 mkg), the C _max in blood plasma (266 pmol/L) was observed in 5 min. after inhalation. At patients from HOBL receiving formoterol in a dose of 12 or 24 mkg 2 times a day for 12 weeks, the concentration of a formoterol in blood plasma defined in 10 min., 2 and 6 h after inhalation were in ranges of 11.5-25.7 and 23.3-50.3 pmol/L respectively.

Definition of total excretion of a formoterol and (or) it (R, R) - and (S, S) - enantiomer showed that the quantity of a formoterol in a blood-groove increases in proportion to the size of the applied dose (12–96 mkg).

After inhalation of 12 or 24 mkg of a formoterol of the fumarat 2 times a day for 12 weeks the removal of a formoterol in not changed view with urine increased from 63 to 73% (the last dose in comparison with the first) at patients OH and from 19 to 38% — at persons with HOBL. These data indicate limited cumulation of a formoterol in blood plasma after multiple dose. After repeated application rather big cumulation of one of enantiomer in comparison with another is noted.

As well as in a case with other medicaments used it is inhalation, it is necessary to expect that the most part of a dose of a formoterol from an inhaler will be swallowed and is absorbed then in a GIT. After intake of 80 mkg of a formoterol of the fumarat, marked ³ N, two healthy volunteers soaked up at least 65% of the accepted dose.

Distribution. Linking of a formoterol with proteins of blood plasma makes 61–64% (first of all binding happens to albumine — 34%). At achievement of therapeutic concentration of a saturation of places of binding does not occur.

Metabolism. The main way of metabolism of a formoterol is the direct glyukuronization. Other way of metabolism — O-demethylation with the subsequent glyukuronization. Other metabolic processes: conjugation of a formoterol with sulfate and a deformilirovaniye after which there is a conjugation of a formoterol to sulfate. O-demethylation and glyukuronization are catalyzed by many isoenzymes (according to UGT 1A1, 1A3, 1A6, 1A7, 1A8, 1A9, 1A10, 2B7, 2B15 and CYP 2D6, 2C19, 2A6) that indicates the small probability of emergence of interaction with other medicines by means of braking of the specific isoenzymes which are taking part in metabolism of a formoterol. Formoterol in therapeutic concentration does not oppress P450 cytochrome isoenzymes.

Removal. At patients from BA or HOBL applying for 12 weeks in a dose 12 or 24 mkg of a formoterol of the fumarat 2 times a day according to about 10 and 7% of a dose it is removed in an invariable form with urine. Enantiomera (R, R) - and (S, S) - made respectively 40 and 60% of quantity of a formoterol in not changed look in urine after reception of one dose (from 12 to 120 mkg) by healthy volunteers and after single and multiple dose by patients OH.

from an organism; near by ² / ₃ dose accepted inside it is removed with urine, and ¹ / ₃ doses — with a stake. The renal clearance of a formoterol is 150 ml/min.

At healthy volunteers of T _½ a formoterola of blood plasma after inhalation of a single dose of 120 mkg of a formoterol of the fumarat is 10 h T _½ enantiomer (R, R) - and (S, S) - calculated on the basis of removal indicators with urine, make respectively 13.9 and 12.3 h

Pharmacokinetic properties of a formoterol at patients of advanced age and at patients with an abnormal liver function or kidneys were not investigated.

Indication

Prevention and treatment of a bronchospasm at patients with oh; prevention of the bronchospasm caused by allergens, cold air or physical activity; prevention and treatment of violations of bronchial passability at patients with hobl, including with chronic bronchitis and emphysema.

Use

Zafiron is appointed for inhalation application for adults and children 6 years are aged more senior.

Adult

BA:1-2 for inhalation (12–24 mkg) 2 times a day. The maximum recommended daily dose for maintenance therapy makes 48 mkg/days. In case of need it is possible to use in addition 1–2 capsules a day for the purpose of reduction of manifestation of symptoms. If the need for application of additional doses of medicine comes more often than 2 days a week, it is necessary to reconsider treatment as it can indicate deterioration in a course of a basic disease.

HOBL: 1–2 capsules for inhalations (12–24 mkg) 2 times a day.

Maximum daily dose for maintenance therapy makes 48 mkg/days

Prevention of the bronchospasm caused by physical activity, allergens or cold air: to inhalate contents of 1 capsule (12 mkg) in 15 min. prior to physical activity or the expected contact with allergen. Use of 2 capsules can be necessary for patients for inhalation (24 mkg) in day from OH heavy current.

Children are aged more senior than 6 years

BA:1 the capsule for inhalation (12 mkg) 2 times in day.

Maximum recommended daily dose makes 24 mkg/days

Prevention of the bronchospasm caused by physical activity, allergens or cold air: it is necessary to inhalate contents of 1 capsule (12 mkg) in 15 min. prior to the expected loading or before the expected contact with allergen.

inhaler Route of administration:

1. To remove a lid nozzle from an inhaler.

2. Holding an inhaler for the lower part, to open it, turning a tip (upper part) on the designated arrow.

3. To place the capsule in the cell which has the form of the capsule and is in the lower part of an inhaler. The capsule should be taken out from packing just before application.

4. To turn a tip in a closed position.

5. To press against the stop the button in the lower part of an inhaler at the same time (only once!), holding an inhaler in vertical position.

ATTENTION! At this moment the capsule can break up and small pieces of gelatin can get into a mouth or a throat. The capsule consists of edible gelatin. Probability of disintegration of the capsule will be minimum if rules of application of an inhaler are followed (the capsule will be unpacked just before application, to puncture the capsule no more once) and storage conditions are sustained.

6. To make a deep exhalation.

7. To take a tip in a mouth and having a little thrown back the head back, lips to clamp a tip and to make several fast uniform and deep breaths. At this moment the capsule begins to rotate in the inhaler camera, and powder to dissipate that is followed by a characteristic sound. If such sound does not appear, so the capsule got stuck in the camera. In this case it is necessary to open an inhaler and to release the capsule. It is forbidden to carry out release of the capsule by repeated pressing the button.

8. At emergence of a characteristic sound (hum), it is necessary to hold the breath as far as it is possible without sensation of discomfort and to take out an inhaler from a mouth. To make an exhalation. Then to open an inhaler and to check whether there was no powder in the capsule. If powder remained, it is necessary to repeat the actions specified in item 6-8.

9. To open an inhaler, to take out the empty used capsule, to turn a tip in a closed position and to put on a lid nozzle.

Clarification of an inhaler: for elimination of residues of powder it is necessary to wipe a tip and the camera for the capsule with a dry napkin or a clean soft brush.

Contraindication

Hypersensitivity to a formoterol or other components of medicine; children's age up to 6 years.

Side effects

Heavy aggravation oh.

more frequent emergence of heavy aggravations OH at the patients accepting formoterol (0.9% in case of a dose of 10-12 mkg 2 times a day, 1.9% — 24 mkg 2 times a day), than at the patients receiving placebo (0.3%) including at children aged from 6 up to 12 years.

Experience of application for teenagers and adult patients with OH

In two large-scale controlled researches conducted during 12 weeks for the purpose of registration of medicine with the maintenance of a formoterol in the American market which included 1095 patients at the age of ≥12 years the heavy aggravations OH (OH aggravation at which hospitalization is necessary) developed more often in case of reception of a formoterol in a dose of 24 mkg 2 times a day (9/271; 3.3%), than at application of a formoterol in a dose of 12 mkg 2 times a day (1/275; 0.4%), intake of placebo (2/277; 0.7%) or Albuterolum (2/277; 0.7%).

2085 patients took part In the following clinical trial which concerned above-mentioned observations. Compared the heavy side effect connected with OH in the groups applying high and lower doses of medicine. The results received in this 16 weeks research did not reveal obvious communication between emergence of this action and a dose of a formoterol. The percent of patients with heavy aggravations OH in this research was slightly higher in case of reception of a formoterol, than in case of use of placebo (in 3 groups with a double blind method: formoterol in a dose of 24 mkg 2 times a day (2/527; 0.4%), formoterol in a dose of 12 mkg 2 times a day (3/527; 0.6%) and placebo (1/514; 0.2%)) and in group with the known medicine (formoterol in a dose of 12 mkg 2 times a day and to two additional doses a day (1/517; 0.2%)).

Experience of application for children aged from 6 up to 12 years with OH

Safety of use of medicine with the maintenance of a formoterol in a dose of 12 mkg 2 times a day, medicine in a dose of 24 mkg 2 times a day and placebo was compared in one big multicenter randomized clinical trial to a double blind method which was conducted during 52 weeks in group with participation of 518 children (aged from 6 up to 12 years) with OH for which daily intake of bronchodilatory and anti-inflammatory medicines was necessary. Heavy aggravations OH appeared more often at the children applying formotreol in a dose of 24 mkg 2 times a day (11/171; 6.4%) or formotreol in a dose of 12 mkg 2 times a day (8/171; 4.7%), than at the children receiving placebo (0/176; 0.0%).

as follows: very often (˃1/10), it is frequent (˃1/100, 1/10), sometimes (˃1/1000, 1/100), is rare (˃1/10,000, 1/1000) and is very rare (1/10,000).

Infrequently — excitement, feeling of alarm, nervousness, insomnia, dizziness

— change of flavoring feelings

Special instructions

a medicine Dose zafiron should be selected according to individual needs of the patient — the minimal effective dose providing therapeutic action. it is not necessary to exceed maximum recommended d