Seretide Diskus 50 mcg. 250 mcg. 60 doses
Patients inadequately controlled background of treatment with inhaled corticosteroids and short-acting B-2 agonist when needed
Seretide Diskus 50 mcg. / 250 mcg. 60 doses
Qualitative and quantitative composition
With each breath Seretide Diskus be taken at 50 ug salmeterol (form of salmeterol xinafoate) and respectively 100, 250 and 500 ug fluticasone propionate.
For excipients, see section 6.1
Powder for inhalation.
Seretide Diskus is indicated for the regular treatment of asthma where it is appropriate to use a combination of long-acting p-2-agonist and inhaled corticosteroid:
Patients with inadequate control of background treatment with inhaled corticosteroids and short-acting B-2 agonist as needed.
Patients with adequately controlled on concomitant inhaled corticosteroid and long-acting B2-agonist.
Note: Use the lowest concentration of Seretide Diskus (salmeterol / fluticasone propionate 50 mcg / 100 ug) is not suitable for adults and children with severe asthma.
Chronic obstructive pulmonary disease
Seretide is indicated for the symptomatic treatment of patients with COPD expressed (with FEV1 <50% predicted normal) with a history of repeated exacerbations with significant symptoms amid regular bronchodilator therapy.
Dosage and method of administration
Seretide Diskus is intended for inhalation.
Patients should be advised that for optimal effect Seretide Diskus should be used daily, even in the absence of symptoms.
Patients should be regularly reassessed by a doctor in order to maintain optimal dosage and dosage of Seretide be changed only with a prescription. The dosage should be adjusted to achieve the lowest optimal dose that maintains effective control of symptoms.
In cases where adequate control of symptoms is maintained with the lowest concentrations of a Seretide Diskus, twice a day, the next step in treatment could include test administration only inhaled corticosteroid. Alternatively, if in the judgment of the treating physician would provide adequate control of symptoms of the disease in patients who require use of long-acting p-agonist may move to Seretide Diskus, administered once daily. In the case of Seretide Diskus was administered once daily if the patient has a history of nocturnal seizures, the drug should be inhaled at night and in patients with symptoms mainly during the day, the dose should be inhaled morning.
Depending on the severity of the disease is given such a concentration of Seretide Diskus, which contains the appropriate dose fluticasone propionate. Doctors who prescribe the drug should be aware that patients with asthma, fluticasone propionate is as effective as other inhaled steroids at approximately halved daily dose in micrograms. For example, 100mg fluticasone propionate is approximately equivalent to 200 mcg beclomethasone dipropionate or budesonide. If you need outside the recommended dosage of Seretide Diskus regimens may be used in appropriate doses of p-agonists and / or corticosteroids.
Adults and adolescents over 12 years:
one inhalation (50 ug salmeterol and 100 ug fluticasone propionate) twice daily or
one inhalation (50 mcg and 250 mcg salmeterol fluticasone propionate) twice daily or
one inhalation (50 mcg and 500 mcg salmeterol fluticasone propionate) twice daily.
Children over 4 years:
one inhalation (50 mcg and 100 mcg salmeterol fluticasone propionate) twice daily. Maximum licensed dose of fluticasone propionate in children Seretide Diskus 100 mcg twice daily.
No information on the use of Seretide in children under 4 years of age.
one inhalation (50 mcg and 500 mcg salmeterol fluticasone propionate) twice daily.
In elderly patients or those with renal impairment is not necessary to adjust the dosage. There are no data on the use of Seredite Diskus in patients with hepatic impairment.
Use a Diskus device
The device is opened and activated by sliding the plunger applicator is then placed in the mouth and lips around it concluded. Inhaled dose and the device is closed.
Seretide Diskus is contraindicated in patients with hypersensitivity to any of the drugs or excipients (see 6.2. List of excipients and their amounts).
Special warnings and precautions for use
Normal treatment of asthma should follow a stepwise program. It is the patient's response to control both clinically and by functional tests of respiratory function.
Seretide Diskus should not be used for relief of acute asthma attack that requires the use of fast-and short-acting bronchodilators. Patients should be advised to have available such a desensitizing agent at any time. Seretide Diskus is not indicated for initial therapy of asthma to establish the need and the approximate dose of corticosteroid.
Increasing use of short-acting bronchodilators for relief of attacks shows worsening disease control and requires examination of the patient.
Sudden and progressive deterioration in asthma control is potentially life threatening and the patient should be consulted urgently by a doctor. In that case, consider increasing the dose of corticosteroids. Where Seretide Diskus in current dose does not provide adequate control of asthma, the patient should also be consulted by a doctor.
In case of need to appoint additional corticosteroid treatment in patients with asthma or COPD.
Treatment with Seretide should not be discontinued abruptly in patients with asthma due to risk of exacerbation. Dose reduction should be done under medical supervision. In patients with COPD, cessation of therapy also may be accompanied by worsening of symptoms, so it should be done under medical supervision.
As with all inhaled drugs containing corticosteroids, Seretide Diskus should be used with caution in patients with pulmonary tuberculosis.
Seretide Diskus should be used with caution in patients with severe cardiovascular disease, incl. arrhythmias, diabetes mellitus, untreated hypokalaemia or thyrotoxicosis.
Rarely reported increase in blood sugar levels (see section 4.8. Undesirable effects), but this should be considered when prescribing to patients with a history of diabetes mellitus.
Potentially serious hypokalaemia may result from systemic therapy with B2-agonists. Upon inhalation therapy at therapeutic doses, however, plasma levels of salmeterol are very low.
As with any other inhalation therapy may develop paradoxical bronchospasm with a sudden increase in wheezing after dosing. Seretide Diskus therapy should be discontinued immediately, the patient should be reviewed and, if necessary, be appointed alternative treatment.
Seretide contains lactose amount of 12,5 mg / dose. This amount does not normally cause problems in patients with lactose intolerance.
When switching to treatment with Seretide need special attention, especially in suspected adrenal system is impaired due to steroid therapy in the past.
As with any inhaled corticosteroid, particularly at high doses for prolonged periods of time may occur systemic reactions, the occurrence of these reactions is less likely than with oral corticosteroids.
Possible systemic effects include Cushing's syndrome and features kashingoidni adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma. It is therefore important that the patient goes to regular reviews and dose of inhaled corticosteroid is adjusted to achieve the lowest possible dose at which effective control over asthma symptoms.
Recommended to regularly measure the height of children receiving long with inhaled corticosteroids.
Prolonged treatment with high doses of inhaled corticosteroids may lead to suppression of the adrenal glands and acute adrenal crisis. Risk is especially increased in children and adolescents under the age of 16 years, receiving high doses fluticasone propionate (typically> 1000 ug per day). There have been very rare cases of suppression of adrenal function and acute adrenal crisis at doses between 500 and less than 1000 ug. Factors that can trigger acute adrenal crisis trauma, surgery, infection or any rapid reduction in dosage. Symptoms are usually vague and may include anorexia, abdominal pain, weight loss, fatigue, headache, nausea, vomiting, hypotension, reduced clarity of consciousness, hypoglycaemia, and seizures. Should be given additional coverage of systemic corticosteroids in patients during periods of stress or elective surgery.
Treatment with inhaled fluticasone propionate reduces the need for oral steroid administration. It should be borne in mind, however, that for a considerable period of time in patients switched from oral corticosteroids, there is a risk of impaired adrenal reserve. A similar risk exists for patients who in the past has imposed emergency corticosteroid therapy in high doses. The possibility of such a breach should always be considered in emergency planning and intervention, likely causing stress, and appropriate corticosteroid treatment discussed. The extent of the adrenal impairment may require specialist advice before elective surgery.
Ritonavir may increase significantly the levels of fluticasone propionate in plasma. For this reason, you should avoid concomitant use unless the potential benefit for the patient outweigh the risk of side effects of systemic corticosteroids. The risk of systemic side effects is increased and when combining fluticasone propionate with other CYP3A inhibitors (see section 4.5 Interactions).
Both non-selective and selective p-blockers should be avoided unless there are compelling reasons for their use.
Concomitant therapy with other p-adrenergic drugs can have a potentially additive effect.
Under normal conditions after inhalation of fluticasone propionate doses to achieve low plasma concentrations due to primary liver metabolism greatly and significant systemic clearance mediated by cytochrome P450 ZA4 in the intestine and liver. It is therefore unlikely that the implementation of clinically significant drug interactions involving fluticasone propionate.
In a study to determine the interaction with intranasally administered fluticasone propionate in healthy subjects has shown that ritonavir (a highly potent inhibitor of cytochrome P450 ZA4) 100 mg twice daily increased several hundred times the plasma concentrations of fluticasone propionate, resulting in a significant reduction in serum cortisol. No information about these effects of inhaled fluticasone propionate, but expect a significant increase in plasma levels. Cases of Cushing's syndrome and adrenal suppression glands. Combining these two drugs should be avoided unless the benefit to the patient outweighs the increased risk of side effects of systemic corticosteroids.
In a small study of healthy volunteers found that slightly weaker inhibitor SURZA ketoconazole increased the exposure of fluticasone propionate after a single inhalation of 150%. This has led to a greater reduction in plasma cortisol levels compared with independent use of fluticasone propionate. Combination therapy with other potent inhibitors such as itraconazole SURZA also expected to increase the systemic exposure to fluticasone propionate and increase the risk of systemic side effects. Careful treatment of this combination and if possible avoid prolonged application.
Pregnancy and lactation
There is insufficient experience in the application of salmeterol xinafoate and fluticasone propionate during pregnancy and lactation in humans. In animal studies with use of B2-adrenoceptor agonists and glucocorticoids, fetal malformations (see section 5.3. Preclinical safety data).
The implementation of the drug during pregnancy should be considered only if the expected benefit to the mother exceeds any possible risk to the fetus.
For the treatment of pregnant women should be used at the lowest effective dose of fluticasone propionate, needed to maintain optimal control of asthma symptoms.
There is no evidence for the transition of salmeterol and fluticasone propionate in human milk. Salmeterol and fluticasone propionate is excreted in rat milk. During lactation Seretide should be used only if the expected benefit to the mother outweighs any possible risk to the child.
Effects on ability to drive and use machines
No specific studies on the effects of Seretide on ability to drive and use machines.
As Seretide contains salmeterol and fluticasone propionate, the type and extent of adverse reactions associated with each of these substances can be made. No case of occurrence of additional adverse events following concurrent administration of the two drugs.
Adverse events associated with salmeterol and fluticasone propionate, are listed below by organ systems affected and the frequency of occurrence. Frequencies are defined as: very common (> 1/10), common (> 1/100 and <1/10), uncommon (> 1/1000 and <1/100) and very rare (<1/10, 000) including isolated reports. Very common, common and uncommon events were generally determined based on data from clinical trials. The incidence of adverse events in placebo not reported. Very rare side effects derived from post-marketing data
Reported to pharmacological adverse reactions with B2-agonists such as tremor, palpitations and headache, they tend to be transient and resolved during lechenieto.Nezhelana reaction of fluticasone propionate is hoarseness and candidiasis of the mouth and throat, which can occur in some patients. Recuperation and candidiasis may be relieved by gargling with water after taking Seretide Diskus. Symptomatic candidiasis can be treated with topical antifungal products with the use of Seretide Diskus.Vazmozhnite systemic effects include Cushing's syndrome and kashingoidni features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma (see 4.4 Special warnings and precautions for use). rarely been reported hyperglycaemia (see section 4.4 Special warnings and precautions for use).
As with other inhaled products may occur paradoxical bronchospasm (see 4.4 Special warnings and precautions for use).
There are no data from clinical trials on overdose with Seretide, but the following are reactions that occur after an overdose of one of the two active ingredients:
Symptoms of overdose salmeterol are tremor, headache and tachycardia. The preferred antidotes are cardioselective p-blockers, which should be used with caution in patients with a history of bronchospasm. If treatment with Seretide, should be stopped due to an overdose of p-agonist in the product should be considered to have an appropriate replacement therapy with corticosteroids. Additional possible hypokalemia. In this case, you must determine the compensation of potassium.
Acute overdose: Inhalation of fluticasone propionate doses than recommended may lead to temporary suppression of adrenal function. This condition does not need emergency action as adrenal function is recovered within a few days, as determined by measuring the level of plasma cortisol.
Chronic overdose of inhaled fluticasone propionate: In this case, appropriate follow-up of adrenal reserve. Overdose of fluticasone propionate treatment with Seretide may still continue with appropriate dosage control symptoms (see section 4.4. Special warnings and special precautions for use).
ATC code: R03AK06
Seretide for asthma - clinical trials
Twelve month study (Gaining Optimal Asthma ControL, GOAL) in 3416 adult and adolescent patients with persistent asthma compared the safety and efficacy of treatment with Seretide and treatment with inhaled corticosteroids (Fliticasone propionate), to determine whether asthma control is achievable. In the treatment concentration was increased at 12 weeks, while achieving complete control ** and start to apply the highest dose of study medication. Data from GOAL showed that more patients treated with Seretide achieved asthma control compared with those treated with inhaled corticosteroids (ICS). In general, this effect was observed earlier in Seretide versus inhaled corticosteroids alone, also at a low dose of inhaled corticosteroid as a component of Seretide.
Well-controlled asthma: rare symptoms or the use of short-acting B2-agonists, or less than 80% of predicted values of pulmonary function will wake up in the morning, no exacerbations and no observed adverse drug reactions requiring change of therapy
Full ** asthma control: no symptoms, no use of short-acting B2-agonists, higher or equal to 80% of predicted values of pulmonary function will wake up in the morning, no exacerbations and no observed adverse drug reactions requiring change therapy
Two further trials in adult and adolescent patients with mild to moderate asthma show that symptom control of asthma can be achieved at a lower dose of inhaled corticosteroid therapy with Seretide compared to treatment with inhaled corticosteroids.
Seretide Diskus for COPD - clinical trials
Results from a placebo-controlled clinical trials conducted over a period of 6 to 12 months have shown that regular use of Seretude Diskus 50/500 ug improves lung function, reduces breathlessness and need to use short-acting medication to ease breathing. For a period of 12 months the risk of exacerbations of COPD decreased from 1.42 to 0.99 for the year compared with the placebo group. The risk of exacerbations leading to the need for oral corticosteroids decreased significantly - from 0.81 to 0.47 per year in the placebo group.
Mechanism of action:
Seretide Diskus contains salmeterol and fluticasone propionate, which act in different ways. The mechanism of action of both drugs is described below:
Salmeterol is a selective long-acting (12 hours) B2-adrenoceptor agonist with a long side chain that binds to the outer part of the receptor.
Salmeterol provides prolonged bronchodilation, lasting for at least 12 hours, compared with conventional Fast acting B2-agonists.
Administered by inhalation at recommended doses of glucocorticoid fluticasone propionate has anti-inflammatory activity in the lung, which gives a result of reduced symptoms and exacerbations of asthma without the side effects seen with systemic corticosteroids.
If concomitant use of fluticasone propionate and salmeterol inhalation pharmacokinetics through each component is similar to that observed in the inhaled administration of each of the ingredients separately.
Therefore, for each pharmacokinetics of the two components can be treated separately
Salmeterol acts locally in the lung and therefore plasma levels are not indicative of the therapeutic effect. Also, there are limited data on the pharmacokinetics of salmeterol because of the technical difficulties to evaluate the drug in plasma due to the low plasma concentrations at therapeutic doses (approximately 200 pg / ml or less), obtainable by inhalation.
The absolute bioavailability of inhaled fluticasone propionate in healthy subjects varies between approximately 10 and 30% of normal dose depending on the device used for inhalation. In patients with asthma or COPD was observed in low systemic exposure.
Systemic absorption takes place mainly in the lung was initially fast, then - continued. The remainder of the inhaled dose may be swallowed, but contributes minimally to systemic exposure due to low water solubility and presystemic metabolism and bioavailability gives a result, less than 1%. By increasing the dose of inhaled observed linear increase in systemic exposure.
The disposition of fluticasone propionate is characterized by high plasma clearance (1150 ml / min), a large volume of distribution at steady state (approximately 3001) and the terminal half-life of approximately 8 hours.
Plasma protein binding is 91%.
Fluticasone propionate is cleared very rapidly from the systemic circulation primarily by metabolism to an inactive carboxylic acid metabolite by the cytochrome P450 enzyme CYP3A4. Other unidentified metabolites were found in feces.
Renal clearance of fluticasone propionate is negligible. Less than 5% of the dose excreted in urine mainly as metabolites. The majority of the dose was excreted in feces as metabolite and unchanged drug.
Preclinical safety data
In animal tests of salmeterol xinafoate and fluticasone propionate, applied separately, the only effects that can affect the safety of medicines in humans are associated with these extraordinary gain their pharmacological actions.
In animal reproductive studies it was observed that glucocorticoids induce malformations (cleft palate, skeletal malformations). Do not assume the results are relevant for humans when used at recommended doses. Animal studies of salmeterol xinafoate have shown developmental toxicity only at high exposure levels.
During concomitant administration of both drugs in rats at doses associated with known glucocorticoid-induced malformations is nablyudavanapovishena incidence of transposed umbilical artery and incomplete ossification of the occipital bone.
List of excipients and their amounts
Lactose monohydrate (contains milk proteins) - up to 12.5 mg
Special precautions for storage
Do not store above 30 ° C. Store in a dry place.
inhalation device molded from plastic containing a strip of film with 28 or 60 equally spaced blisters.
Recommendations for use
Powder Diskus inhalation device releases a powder that is inhaled into the lungs.
Diskus doses of a counter that shows the remaining doses.
In the leaflet Patient Information contained detailed instructions.