Fludalt Duo

Fludalt Duo

salmeterol + fluticasone

Manufacturer:

Favorex

Distributor:

DKSH
Full Prescribing Info
Contents
Fluticasone propionate, salmeterol xinafoate.
Description
Each capsule provides: 250 microgram of fluticasone propionate and 50 microgram of salmeterol (as salmeterol xinafoate).
Excipients/Inactive Ingredients: Lactose monohydrate.
Action
Pharmacology: Pharmacodynamics: Mechanism of Action: Fluticasone / Salmeterol contain salmeterol and fluticasone propionate which have differing modes of action. Salmeterol protects against symptoms, fluticasone propionate improves lung function and prevents exacerbations of the condition. Fluticasone / Salmeterol can offer a more convenient regime for patients on concurrent β-agonist and inhaled corticosteroid therapy. The respective mechanisms of action of both drugs are discussed as follows: Salmeterol: Salmeterol is a selective long-acting (12-hr) β2-adrenoreceptor agonist with a long side chain which binds to the exo-site of the receptor.
These pharmacological properties of salmeterol offer more effective protection against histamine-induced bronchoconstriction and produce a longer duration of bronchodilation, lasting for at least 12hrs than recommended doses of conventional short-acting β2-agonists.
In vitro tests have shown salmeterol is a potent and long-lasting inhibitor of the release, from human lung, of mast cell mediators eg, histamine, leukotrienes and prostaglandin D2.
In man, salmeterol inhibits the early and late phase response to inhaled allergen; the latter persisting for over 30 hrs after a single dose when the bronchodilator effect is no longer evident. Single dosing with salmeterol attenuates bronchial hyper-responsiveness. These properties indicate that salmeterol has additional non-bronchodilator activity but the full clinical significance is not yet clear. This mechanism is different from the anti-inflammatory effect of corticosteroids.
Fluticasone Propionate: Fluticasone propionate given by inhalation at recommended doses has a potent glucocorticoid anti-inflammatory action within the lungs, resulting in reduced symptoms and exacerbations of asthma, without the adverse effects observed when corticosteroids are administered systematically.
Daily output of adrenocortical hormones usually remains within the normal range during chronic treatment with inhaled fluticasone propionate, even at the highest recommended doses in children and adults. After transfer from other inhaled steroids, the daily output gradually improves despite past and present intermittent use of oral steroids, thus demonstrating return of normal adrenal function on inhaled fluticasone propionate. The adrenal reserve also remains normal during chronic treatment, as measured by a normal increment on a stimulation test. However, any residual impairment of adrenal reserve from previous treatment may persist for a considerable time and should be borne in mind (see Precautions).
Pharmacokinetics: When salmeterol and fluticasone propionate were administered in combination by the inhaled route, the pharmacokinetics of each component were similar to those observed when the drugs were administered separately. For pharmacokinetic purposes therefore each component can be considered separately.
Salmeterol: Salmeterol acts locally in the lung therefore plasma levels are not an indication of therapeutic effects. In addition there are only limited data available on the pharmacokinetics of salmeterol because of the technical difficulty of assaying the drug in plasma due to the low plasma concentrations at therapeutic doses (approximately 200 picogram /ml or less) achieved after inhaled dosing.
Fluticasone propionate: The absolute bioavailability of a single dose of inhaled fluticasone propionate in healthy subjects varies between approximately 5-11% of the nominal dose depending on the inhalation device used. In patients with asthma or COPD a lesser degree of systemic exposure to inhaled fluticasone propionate has been observed.
Systemic absorption occurs mainly through the lungs and is initially rapid then prolonged. The remainder of the inhaled dose may be swallowed but contributes minimally to systemic exposure due to the low aqueous solubility and pre-systemic metabolism, resulting in oral availability of less than 1%. There is a linear increase in systemic exposure with increasing inhaled dose.
The disposition of fluticasone propionate is characterized by high plasma clearance (1150 mL/min), a large volume of distribution at steady- state (approximately 300 L) and a terminal half-life of approximately 8 hours.
Plasma protein binding is 91%.
Fluticasone propionate is cleared very rapidly from the systemic circulation. The main pathway is metabolism to an inactive carboxylic acid metabolite, by the cytochrome P450 enzyme CYP3A4. Other unidentified metabolites are also found in the faeces.
The renal clearance of fluticasone propionate is negligible. Less than 5% of the dose is excreted in urine, mainly as metabolites. The main part of the dose is excreted in faeces as metabolites and unchanged drug.
Indications/Uses
Reversible Obstructive Airways Disease (ROAD): Fludalt DUO is indicated in the regular treatment of ROAD, including asthma in children and adults, where use of a combination (bronchodilator and inhaled corticosteroid) is appropriate.
This may include: Patients on effective maintenance doses of long- acting β-agonists and inhaled corticosteroids.
Patients who are symptomatic on current inhaled corticosteroid therapy.
Patients on regular bronchodilator therapy who require inhaled corticosteroids.
Chronic Obstructive Pulmonary Disease (COPD): Fludalt DUO is indicated in the regular treatment of COPD including chronic bronchitis and emphysema.
Dosage/Direction for Use
Fludalt DUO is for inhalation use only.
Recommended Doses: Reversible Obstructive Airways Disease (ROAD): Adults and adolescents 12 years and older: One inhalation (50 mcg salmeterol and 250 mcg fluticasone propionate) twice daily.
There are no data available for use of Salmeterol/Fluticasone in children aged under 4 years.
Use of Salmeterol / Fluticasone for Inhaled Corticosteroid Sparing: Adults and adolescents 12 years and older, with stable asthma who require fluticasone propionate 250 micrograms twice daily or equivalent to maintain control of their asthma; this dose may be replaced with one inhalation (50 micrograms salmeterol and 100 micrograms fluticasone propionate) twice daily.
Chronic Obstructive Pulmonary Disease (COPD): For adult patients the recommended dose is one inhalation 50/250 mcg to 50/500 mcg salmeterol/fluticasone propionate twice daily.
Special patient groups: There is no need to adjust the dose in elderly patients or in those with renal or hepatic impairment.
Method of administration: Instruction for use: 1. Pull off the cap.
2. Hold the base of the inhaler firmly and turn the mouthpiece in the direction of the arrow to open.
3. Take one of today's capsules. Place it in the capsule-shaped compartment in the base of the inhaler. It is important that the patient remove the capsule from the pack only immediately before the patient use it.
4. Twist the mouthpiece to the closed position until it clicks.
5. Keeping the inhaler upright, firmly squeeze the two buttons once only. This will pierce the capsule. Release the buttons. Although the capsule is now pierced, the powder will not be released until the patient inhale it.
6. Breathe out fully.
7. Place the mouthpiece in the mouth and tilt the head slightly backwards. Close the lips around the mouthpiece and breathe in as quickly and as deeply as the patient can. As the patient breathe in, the patient will inhale the medicine into the lungs.
The patient should hear the capsule spinning in the inhaler. If the patient do not hear this whirring noise, the capsule may be stuck in the compartment. If this occurs, open the inhaler and loosen the capsule by pressing it out of the compartment. Do not try to loosen the capsule by repeatedly pressing the buttons.
8. If the patient have heard the whirring noise, hold the breath for as long as the patient comfortably can while taking the inhaler out of the mouth. Then breathe normally. Open the inhaler to see if any powder is still in the capsule. If there is still powder in the capsule repeat steps 6 to 8.
9. After use, tip out the empty capsule and close the mouthpiece.
10. Place back the protective cap.
11. If the patient need to clean the inhaler, wipe the mouthpiece and capsule compartment with a dry cloth or a clean soft brush.
Overdosage
The signs and symptoms of salmeterol overdose are tremor, headache and tachycardia. The preferred antidotes are cardioselective beta-blocking agents, which should be used with caution in patients with a history of bronchospasm. If Fludalt DUO therapy has to be withdrawn due to overdose of the beta agonist component of the drug, provision of appropriate replacement steroid therapy should be considered. Additionally, hypokalaemia can occur and potassium replacement should be considered.
Contraindications
Hypersensitivity to the active substance(s) or to any of the excipients - Lactose monohydrate.
Special Precautions
The management of ROAD should normally follow a stepwise programme and patient response should be monitored clinically and by lung function tests.
Fluticasone / Salmeterol is not for relief of acute symptoms for which a fast- and short-acting bronchodilator (eg, salbutamol) is required. Patients should be advised to have their relief medication available at all times. Increasing use of short-acting bronchodilators to relieve symptoms indicates deterioration of control and patients should be reviewed by a physician.
Sudden and progressive deterioration in control of asthma is potentially life-threatening and the patient should be reviewed by a physician. Consideration should be given to increasing corticosteroid therapy. Also, where the current dosage of Fluticasone /Salmeterol has failed to give adequate control of ROAD, the patient should be reviewed by a physician.
Fluticasone / Salmeterol should not be initiated in patients with unstable and acutely deteriorating asthma, which may be a life-threatening condition. Serious acute respiratory events, including fatalities, have been reported when salmeterol has been initiated in this situation. Although, it is not possible from these reports to determine whether salmeterol contributed to these adverse events or failed to relieve the deteriorating asthma, the use of salmeterol in this setting is inappropriate.
Treatment with Fluticasone / Salmeterol should not be stopped abruptly in patients with asthma due to risk of exacerbation, therapy should be titrated-down under physician's supervision. For patients with COPD, cessation of therapy may be associated with symptomatic decompensation and should be supervised by a physician.
There was an increased reporting of pneumonia in studies of patients with COPD receiving Fluticasone / Salmeterol (see Adverse Reactions). Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbation frequently overlap. As with all inhaled medication containing corticosteroids, Fluticasone / Salmeterol should be administered with caution in patients with active or quiescent pulmonary tuberculosis.
Fluticasone / Salmeterol should be administered with caution in patients with thyrotoxicosis.
Cardiovascular effects eg, increases in systolic blood pressure and heart rate, may occasionally be seen with all sympathomimetic drugs, especially at higher than therapeutic doses. For this reason, Fluticasone / Salmeterol should be used with caution in patients with preexisting cardiovascular disease.
A transient decrease in serum potassium may occur with all sympathomimetic drugs at higher therapeutic doses. Therefore, Fluticasone / Salmeterol should be used with caution in patients predisposed to low levels of serum potassium.
Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods; these effects are much less likely to occur than with oral corticosteroids (see Overdosage). Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma.
It is important, therefore for ROAD patients, that the dose of inhaled corticosteroid is titrated to the lowest dose at which effective control is maintained. The possibility of impaired adrenal response should always be borne in mind in emergency and elective situations likely to produce stress and appropriate corticosteroid treatment considered (see Overdosage).
Certain individuals can show greater susceptibility to the effects of inhaled corticosteroid than do most patients.
Because of the possibility of impaired adrenal response, patients transferring from oral steroid therapy to inhaled fluticasone propionate therapy should be treated with special care, and adrenocortical function regularly monitored.
Following introduction of inhaled fluticasone propionate, withdrawal of systemic therapy should be gradual and patients encouraged to carry a steroid warning card indicating the possible need for additional therapy in times of stress.
Patients in a medical or surgical emergency, who in the past have required high doses of inhaled steroids and/or intermittent treatment with oral steroids, remain at risk of impaired adrenal reserve for a considerable time. The extent of the adrenal impairment may require specialist's advice before elective procedures. The possibility of residual impaired adrenal response should always be borne in mind in emergency and elective situation likely to produce stress and appropriate corticosteroid treatment must be considered.
Use in children: It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroid is regularly monitored.
There are no data available for use of Fluticasone / Salmeterol in children <4 years.
Effects on ability to drive and use machines: No studies of the effect on the ability to drive and use machines have been performed.
Use In Pregnancy & Lactation
Fertility, pregnancy and lactation: Administration of drugs during pregnancy and lactation should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus or child. There is insufficient experience of the use of salmeterol xinafoate and fluticasone propionate in human pregnancy and lactation.
Pregnancy: Reproductive toxicity studies in animals, either with single drug or in combination, revealed the foetal effects expected at excessive systemic exposure levels of a potent β2-adrenoreceptor agonist and glucocorticosteroid.
Lactation: Salmeterol and fluticasone propionate concentrations in plasma after inhaled therapeutic doses are very low and therefore, concentrations in human breast milk are likely to be correspondingly low. This is supported by studies in lactating animals, in which low drug concentrations were measured in milk. There are no data available for human breast milk.
Adverse Reactions
As Fludalt DUO contains salmeterol and fluticasone propionate, the type and severity of adverse reactions associated with each of the compounds may be expected. There is no incidence of additional adverse events following concurrent administration of the 2 compounds.
As with other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with a fast- and short- acting inhaled bronchodilator. Salmeterol/fluticasone propionate should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary. Adverse events which have been associated with salmeterol or fluticasone propionate are as follows: Salmeterol: The pharmacological adverse effects of β2-agonist treatment eg, tremor, subjective palpitations and headache, have been reported, but tend to be transient and reduce with regular therapy.
Cardiac arrhythmias (including atrial fibrillation, supraventricular tachycardia and extrasystoles) may occur, usually in susceptible patients.
There have been very rare reports of anthralgia.
Hypersensitivity reactions, including anaphylactic reactions eg, oedema and angioedema, bronchospasm and anaphylactic shock have been reported rarely. There have been reports of rash.
There have been common reports of muscle cramps.
There have been very rare reports of hyperglycaemia.
Fluticasone Propionate: Hoarseness and candidiasis (thrush) of the mouth and throat can occur in some patients.
There have been uncommon reports of cutaneous hypersensitivity reactions. There have also been rare reports of hypersensitivity reactions manifesting as angioedema (mainly facial and oropharyngeal oedema), respiratory symptoms (dyspnoea and/or bronchospasm) and very rarely, anaphylactic reactions.
Both hoarseness and incidence of candidiasis may be relieved by gargling with water after use of salmeterol/fluticasone propionate. Symptomatic candiasis can be treated with topical antifungal therapy while still continuing with salmeterol/fluticasone propionate.
Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma (see Precautions). There have been very rare reports of hyperglycaemia.
There have been very rare reports of anxiety, sleep disorders and behavioural changes including hyperactivity and irritability (predominantly in children).
Drug Interactions
Both nonselective and selective β-blockers should be avoided unless there are compelling reasons for their use.
Under normal circumstances, low plasma concentrations of fluticasone propionate are achieved after inhaled dosing, due to extensive first- pass metabolism and high systemic clearance mediated by CYP-450 3A4 in the gut and liver. Hence, clinically significant drug interactions mediated by fluticasone propionate are unlikely.
Ritonavir (a highly potent CYP-450 3A4 inhibitor) can greatly increase fluticasone propionate plasma concentrations, resulting in markedly reduced serum cortisol concentrations.
Other inhibitors of CYP-450 3A4 produce negligible (erythromycin) and minor (ketoconazole) increase in systemic exposure to fluticasone propionate without notable reductions in serum cortisol concentrations. Nevertheless, care is advised when co-administering potent CYP-450 3A4 inhibitors (eg, ketoconazole) as there is potential for increased systemic exposure to fluticasone propionate.
Co-administration of ketoconazole and salmeterol can result in a significant increase in plasma salmeterol exposure (1.4-fold Cmax and 15-fold AUC) and this may cause a prolongation of the QTc interval (see Pharmacology: Pharmacokinetics under Actions and Precautions).
Caution For Usage
Incompatibilities: Not applicable.
Storage
Store below 30°C.
Shelf-Life: 2 years.
ATC Classification
R03AK06 - salmeterol and fluticasone ; Belongs to the class of adrenergics in combination with corticosteroids or other drugs, excluding anticholinergics. Used in the treatment of obstructive airway diseases.
Presentation/Packing
250/50 mcg inhalation powd (colourless capsules containing white or almost white) 60's.
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