Seretide Aerosol, 120 d, 25+250 mcg/dose, for inhalation

Seretide Aerosol, 120 d, 25+250 mcg/dose, for inhalation

special instructions

Seretide is not intended for the relief of acute symptoms, as in such cases a rapid and short-acting inhaled bronchodilator (eg salbutamol) should be used. Patients should be advised to always have medication available to relieve acute symptoms. The combination of salmeterol and fluticasone propionate can be used for initial maintenance therapy in patients with persistent bronchial asthma (daily occurrence of symptoms or daily use of drugs to relieve attacks) if there are indications for the use of corticosteroids and their approximate dosage has been determined. More frequent use of short-acting bronchodilators to relieve symptoms indicates worsening disease control, and in such situations the patient should consult a doctor. Sudden and increasing deterioration in control of bronchospastic syndrome poses a potential threat to life, and in such situations the patient should also consult a doctor. The physician should consider prescribing a higher dose of GCS. If the dose of Seretide used does not provide adequate control of the disease, the patient should also consult a doctor. Patients with asthma should not abruptly stop treatment with Seretide due to the risk of exacerbation; the dose of the drug should be reduced gradually under the supervision of a physician. In patients with COPD, drug withdrawal may be accompanied by symptoms of decompensation and requires medical supervision. Clinical studies have provided evidence of an increase in the incidence of pneumonia in patients with COPD receiving Seretide (see section Side effects). Clinicians should be aware of the possibility of developing pneumonia in COPD, since the clinical presentation of pneumonia and exacerbation of COPD are often similar. Any inhaled GCS can cause systemic effects, especially with long-term use in high doses; however, the likelihood of such symptoms occurring is much lower than with treatment with oral corticosteroids (see Overdose section). Possible systemic reactions include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts, and glaucoma. Therefore, when treating asthma, it is important to reduce the dose to the lowest dose that provides effective control of the disease. In emergency and planned situations that can cause stress, it is always necessary to remember the possibility of adrenal suppression and be prepared to use GCS (see section Overdose). When carrying out resuscitation measures or surgical interventions, it is necessary to determine the degree of adrenal insufficiency. It is recommended to regularly measure the height of children who receive long-term therapy with inhaled corticosteroids. Due to the possibility of adrenal suppression, patients switched from oral corticosteroids to inhaled fluticasone propionate therapy should be treated with extreme caution and their adrenal function regularly monitored. After starting treatment with inhaled fluticasone propionate, systemic corticosteroids should be withdrawn gradually, and such patients should have a special patient card containing an indication of the possible need for additional administration of corticosteroids in stressful situations. In patients with exacerbation of bronchial asthma, hypoxia, it is necessary to control the concentration of K+ ions in the plasma. There are very rare reports of increased blood glucose levels, and this should be kept in mind when prescribing a combination of salmeterol and fluticasone propionate to patients with diabetes mellitus (see section Side effects). During the post-marketing period, there have been reports of clinically significant drug interactions between fluticasone propionate and ritonavir, leading to systemic effects of GCS, including Cushing's syndrome and adrenal suppression. Therefore, it is recommended to avoid the combined use of fluticasone propionate and ritonavir, except in cases where the potential benefit to the patient outweighs the risk associated with the systemic effects of GCS (see section Drug Interactions). Data from a clinical study of the safety of salmeterol added to the treatment of bronchial asthma compared with placebo showed that the incidence of deaths due to bronchial asthma was significantly higher in the salmeterol group. When taking salmeterol compared with placebo, the risk of serious respiratory adverse reactions or death in African-American patients appears to be greater than in other patients. The significance of pharmacogenetic factors or other causes is unknown. The effect associated with the use of GCS on the risk of death in patients with asthma was not studied in this study. Like other inhaled drugs, Seretide can cause paradoxical bronchospasm, manifested by an increase in shortness of breath immediately after use. In this case, you should immediately use a fast- and short-acting inhaled bronchodilator, discontinue the drug Seretide, examine the patient and, if necessary, begin alternative therapy (see section Side effects). There are reports of adverse reactions associated with the pharmacological action of beta2-antagonists, such as tremor, subjective palpitations and headache. However, these reactions are short-term in nature, and their severity decreases with regular therapy (see section Side effects). Effect on the ability to drive vehicles and operate machinery In clinical studies, no data were obtained on the effect of the drug on the ability to drive vehicles and other mechanisms, however, side effects that the drug may cause should be taken into account.

Composition and release form

Seretide®

120 doses in an aluminum inhaler (complete with dosing device); in a cardboard box 1 inhaler.

Seretide® Multidisc®

in a round plastic inhaler 1 blister with 28 or 60 cells; There is 1 inhaler in a cardboard pack.

Overdose

Symptoms: objective and subjective symptoms of salmeterol overdose include tremor, headache and tachycardia. Inhalation of doses of fluticasone propionate higher than recommended may cause temporary depression of the hypothalamic-pituitary-adrenal axis. This usually does not require any emergency measures, since in most cases normal adrenal function is restored within a few days.

With prolonged inhalation of excessively large doses of Seretide® and Seretide® Multidisc, significant adrenal suppression may occur. There are rare reports in the literature of acute adrenal crisis, which occurs predominantly in children receiving excessively high doses over a long period of time (several months or years); acute adrenal crisis is manifested by hypoglycemia, accompanied by confusion and/or convulsions. Situations that may trigger an acute adrenal crisis include trauma, surgery, infection, or a rapid reduction in the dose of fluticasone propionate.

Treatment: antidotes are cardioselective β-blockers. In cases where it is necessary to discontinue the drugs Seretide® and Seretide® Multidisk due to an overdose of salmeterol included in its composition, the patient should be prescribed an appropriate replacement GCS.

Patients should be aware that they should not take Seretide® and Seretide® Multidisk in doses higher than recommended. It is important to regularly assess the effectiveness of therapy and reduce the dose to the minimum effective, i.e. to one that provides effective control of disease symptoms.

In case of chronic overdose, it is recommended to monitor the reserve function of the adrenal cortex.

Description of the dosage form

Aerosol for inhalation metered Seretide®: inhaler - aluminum with a concave bottom, hermetically sealed with a metering valve; the internal surface of the inhaler and valve should not have visible defects.

The contents of the inhaler are a white or almost white suspension.

Powder for inhalation metered Seretide® Multidisc®: inhaler - a round plastic device of 2 shades of purple (dark purple and light purple) with a diameter of about 8.5 cm and a height of about 3 cm, with a dose counter showing 28 or 60 doses.

The contents of the inhaler are white or almost white powder.

Pharmacokinetics

When administered together by inhalation, salmeterol and fluticasone propionate do not affect each other's pharmacokinetics, therefore the pharmacokinetic characteristics of each component of Seretide® and Seretide® Multidisk can be considered separately.

Even despite the very low plasma concentrations of salmeterol and fluticasone propionate, interactions with other substrates and inhibitors of the CYP3A4 isoenzyme cannot be excluded.

Salmeterol: acts locally in the lung tissue, so its plasma levels do not correlate with the therapeutic effect. Data on its pharmacokinetics are very limited due to technical problems: when inhaled in therapeutic doses, its Cmax in plasma is extremely low (about 200 pg/ml and below). After repeated inhalations of salmeterol xinafoate, hydroxynaphthoic acid can be detected in the blood, the Css of which is about 10 pg/ml. These concentrations are 1000 times lower than equilibrium levels observed in toxicity studies.

Fluticasone propionate: The absolute bioavailability of inhaled fluticasone propionate in healthy subjects varies depending on the inhaler used (when using salmeterol/fluticasone propionate using a metered dose inhalation aerosol, it is 5.3% of the nominal dose). In patients with bronchial asthma and COPD, lower plasma concentrations of fluticasone propionate are observed. Systemic absorption occurs primarily through the lungs, and is initially faster but then slows down.

Part of the inhalation dose may be swallowed, but this part makes a minimal contribution to systemic absorption due to the low solubility of the drug in water and due to its first-pass metabolism. Bioavailability from the gastrointestinal tract is less than 1%. As the inhalation dose increases, a linear increase in the plasma concentration of fluticasone propionate is observed. The distribution of fluticasone propionate is characterized by rapid plasma clearance (1150 ml/min), a large Vss (about 300 l) and a final half-life of approximately 8 hours. Fluticasone propionate has a relatively high degree of plasma protein binding (91%). It is rapidly eliminated from the blood, mainly as a result of metabolism under the action of the CYP3A4 isoenzyme to an inactive carboxyl metabolite.

Renal clearance of unchanged fluticasone propionate is negligible (<0.2%), less than 5% of the dose is excreted in the urine as a metabolite. Caution must be exercised when using known CYP3A4 inhibitors and fluticasone propionate simultaneously, since in such situations the plasma levels of the latter may increase.

It is excreted through the gastrointestinal tract, mainly in the form of a hydroxylated metabolite.

Contraindications

hypersensitivity to the components of the drug;

children under 4 years of age.

With caution: pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system, thyrotoxicosis, pheochromocytoma, diabetes mellitus, uncontrolled hypokalemia, idiopathic hypertrophic subaortic stenosis, uncontrolled arterial hypertension, arrhythmias, prolongation of the QT interval on the ECG, ischemic heart disease, hypoxia of various origins, cataracts, glaucoma, hypothyroidism, osteoporosis, pregnancy, lactation.

Directions for use and doses

To obtain the optimal effect, the drug should be used regularly, even in the absence of clinical symptoms of bronchial asthma and COPD. Determining the duration of the course of therapy and changing the dose of the drug is possible only on the recommendation of a doctor. The patient should be prescribed a dosage form of Seretide® or Seretide® Multidisk that contains a dose of fluticasone propionate appropriate to the severity of his disease.

If a patient is unable to achieve adequate disease control with inhaled corticosteroid monotherapy, switching to combination therapy with salmeterol and fluticasone propionate at an equivalent corticosteroid dose may result in improved asthma control. For those patients in whom monotherapy with an inhaled corticosteroid provides adequate control of bronchial asthma, switching to inhaled therapy with a combination of salmeterol and fluticasone propionate may allow a reduction in the dose of the corticosteroid without loss of control of bronchial asthma.

Seretide®

Inhalation, intended for inhalation only.

Recommended Doses

Adults and children 12 years of age and older: 2 inhalations (25 mcg salmeterol and 50 mcg fluticasone propionate) 2 times a day or 2 inhalations (25 mcg salmeterol and 125 mcg fluticasone propionate) 2 times a day, or 2 inhalations (25 mcg salmeterol and 250 mcg of fluticasone propionate) 2 times a day.

Children 4 years and older: 2 inhalations (25 mcg salmeterol and 50 mcg fluticasone propionate) 2 times a day.

Currently, there is no data on the use of Seretide® in children under 4 years of age.

The dose of Seretide should be reduced to the lowest dose that provides effective control of symptoms. If control of symptoms is ensured by taking Seretide® 2 times a day, reducing the dose to the minimum effective may include a single dose of the drug per day.

COPD

For adult patients, the maximum recommended dose is 2 inhalations (25 mcg of salmeterol and 250 mcg of fluticasone propionate) 2 times a day.

Special patient groups

There is no need to reduce the dose in elderly patients or in patients with impaired renal or hepatic function.

Seretide® Multidisc

Inhalation, intended for inhalation only.

Recommended Doses

Adults and children 12 years of age and older: 1 inhalation (50 mcg salmeterol and 100 mcg fluticasone propionate) 2 times a day or 1 inhalation (50 mcg salmeterol and 250 mcg fluticasone propionate) 2 times a day, or 1 inhalation (50 mcg salmeterol and 500 mcg of fluticasone propionate) 2 times a day.

In adults over 18 years of age, doubling the dose while using any form of Seretide® Multidisk for up to 14 days maintains the same safety and tolerability as with regular use of this combination, 1 inhalation 2 times a day. The dose may be doubled in cases where patients require additional short-term (up to 14 days) inhaled corticosteroid therapy, as described in some asthma treatment guidelines.

Children 4 years of age and older: 1 inhalation (50 mcg of salmeterol and 100 mcg of fluticasone propionate) 2 times a day.

There is currently no data on the use of Seretide® Multidisk in children under 4 years of age.

COPD

For adult patients, the maximum recommended dose is 1 inhalation (50 mcg of salmeterol and 500 mcg of fluticasone propionate) 2 times a day.

Special patient groups

There is no need to reduce the dose in elderly patients or in patients with impaired renal or hepatic function.

Seretide®

Instructions for use of the inhaler

Checking the inhaler: before using the inhaler for the first time or if the inhaler has not been used for a week or longer, you must remove the cap from the mouthpiece by lightly squeezing the cap on the sides, shake the inhaler well and release 1 stream into the air to make sure it is working.

Using an inhaler

1. Remove the cap from the mouthpiece by lightly squeezing the cap from the sides.

2. Inspect the inhaler inside and out, including the mouthpiece, for loose parts.

3. Shake the inhaler well to ensure that any loose parts are removed and that the contents of the inhaler are evenly mixed.

4. Hold the inhaler between your thumb and the other four fingers in a vertical position, bottom up, with your thumb resting on the base under the mouthpiece.

5. Exhale as deeply as possible, then place the mouthpiece in your mouth between your teeth, closing your lips around it without biting.

6. Immediately after you start inhaling through your mouth, press the top of the inhaler to spray Seretide® while continuing to inhale deeply and slowly.

7. While holding your breath, remove the inhaler from your mouth and remove your finger from the top of the inhaler. Continue holding your breath for as long as possible.

8. To carry out the second spray, hold the inhaler vertically and after about 30 seconds repeat steps 3–7.

9. After using the inhaler, rinse your mouth with water and then spit it out.

10. Close the mouthpiece cap by pressing and snapping into position.

The drug can also be used through a spacer (for example Volumatic).

Attention! When following steps 4, 5 and 6, you should not rush. You should begin inhaling as slowly as possible, just before pressing the inhaler valve. It is recommended to practice in front of a mirror the first few times. If you see a "fog" coming from the top of the inhaler or from the corners of your mouth, then you should start over from step 2.

If your doctor has given other instructions for using your inhaler, you should strictly follow them. You should contact your doctor if you have difficulty using your inhaler.

Using an inhaler in children

Young children cannot use the inhaler themselves and must be assisted by an adult. It is necessary to wait until the child exhales and activate the inhaler at the moment the child begins to inhale. You should practice using the inhaler with your child. Older children and adults with weak hands should hold the inhaler with both hands. In this case, both index fingers should be located on the top of the inhaler, and both thumbs should be on the base below the mouthpiece. For children, the drug is administered using an inhaler through a spacer with a face mask (for example, Babyhaler).

Cleaning the inhaler: the inhaler must be cleaned at least once a week. Remove the protective cap from the mouthpiece. Do not remove the metal can from the plastic casing. Use a dry cloth or cotton swab to wipe the mouthpiece inside and out and the plastic casing outside. Close the mouthpiece with the protective cap.

Do not immerse the metal can in water.

Seretide® Multidisc

Instructions for use of the inhaler

Inhaler device

Multidisk is closed (Fig. 1)

Multidisk is open (Fig. 2)

The inhaler has an indicator that, after inhalation, shows the number of remaining doses. The numbers are in descending order from 60 to 0. Numbers from 5 to 0 are red, indicating that there are only a few doses left in the inhaler. The appearance of the number 0 in the window means that the inhaler is empty and unsuitable for further use.

Using an inhaler

To carry out inhalation, follow 4 sequential steps:

1) open the inhaler;

2) press the lever,

3) inhale a dose of the drug;

4) close the inhaler;

5) rinse your mouth with water.

1. Open the inhaler (Fig. 3).

You should hold the body with one hand, placing the thumb of the other hand in a special recess. To open the inhaler, you need to press your thumb away from you until it clicks.

2. Press the lever (Fig. 4).

You must hold the inhaler with the mouthpiece towards your face. The inhaler can be held with your right or left hand. Press the lever away from you until it stops until you hear a click. The inhaler is now ready for use. After pressing the lever, another cell with powder for inhalation is opened. In this case, the number of remaining doses decreases, which is indicated in the indicator window. You should press the lever only before inhalation, otherwise this will lead to wastage of the drug.

3. Inhale a dose of medicine (Fig. 5).

You should hold the inhaler at some distance from your mouth and exhale deeply without force.

Remember: never exhale into an inhaler!

You need to wrap your lips tightly around the mouthpiece. Take a slow, deep breath through your mouth (not your nose).

Remove the inhaler from your mouth.

Hold your breath for about 10 seconds or longer as possible.

Exhale slowly. Do not exhale into the inhaler.

4. Close the inhaler (Fig. 6)

In order to close the inhaler, you need to place your thumb in a special recess and press towards you until it stops until you hear a click. The lever automatically returns to its original position.

5. After using the drug, rinse your mouth with water and spit it out.

Cleaning the inhaler: After using the inhaler, the mouthpiece should be wiped with a dry cloth.