Salmeterol Multicenter Asthma Research Trial (SMART): A 28-week, placebo-controlled, U.S. trial that compared the safety of salmeterol with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in subjects receiving salmeterol (13/13,176 in subjects treated with salmeterol versus 3/13,179 in subjects treated with placebo; relative risk: 4.37 [95% CI: 1.25, 15.34]). One subject (3%) who received fluticasone propionate and salmeterol inhalation powder 250 mcg/50 mcg had an abnormal response (peak serum cortisol less than 18 mcg/dL) after dosing, compared with 2 subjects (6%) who received placebo, 2 subjects (6%) who received fluticasone propionate 250 mcg, and no subjects who received salmeterol. Increasing use of inhaled, short-acting beta2-agonists is a marker of deteriorating asthma. The medication cannot be administered in children under 4 y.o. Salmeterol is a selective LABA. Fluticasone propionate and salmeterol inhalation powder should be stored inside the unopened moisture-protective foil pouch and only removed from the pouch immediately before initial use. It was not possible from these reports to determine whether salmeterol contributed to these events. The fourth trial included pediatric subjects aged 4 to 11 years and compared fluticasone propionate/salmeterol inhalation powder with fluticasone propionate inhalation powder [see Clinical Studies (14.1)]. In addition, fluticasone propionate and salmeterol inhalation powder 250 mcg/50 mcg was superior to fluticasone propionate, salmeterol, and placebo for improvements in morning and evening PEF. The effects of rising inhaled doses of salmeterol and standard inhaled doses of albuterol were studied in volunteers and in subjects with asthma. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to fluticasone propionate and salmeterol inhalation powder, fluticasone propionate, and/or salmeterol or a combination of these factors. The safety and effectiveness of fluticasone propionate and salmeterol inhalation powder in children with asthma younger than 4 years have not been established. The most common events that occurred with a frequency of >5% and more frequently in the subjects treated with fluticasone propionate and salmeterol inhalation powder were nasopharyngitis, upper respiratory tract infection, nasal congestion, back pain, sinusitis, dizziness, nausea, pneumonia, candidiasis, and dysphonia. Active ingredients: fluticasone propionate USP, salmeterol xinafoate USP, Inactive ingredient: lactose monohydrate (contains milk proteins). Higher fluticasone propionate exposure from fluticasone propionate and salmeterol inhalation powder 100 mcg/50 mcg compared with FLOVENT DISKUS 100 mcg was observed in adolescents and adults (ratio 1.52 [90% CI: 1.08, 2.13]). Hypersensitivity to fluticasone, salmeterol, or any component of the formulation; status asthmaticus; acute episodes of asthma or COPD; severe hypersensitivity to milk proteins (Advair Diskus, AirDuo RespiClick)Documentation of allergenic cross-reactivity for corticosteroids and sympathomimetics are limited. BMD evaluations were conducted at baseline and at 48, 108, and 158 weeks. Salmeterol: In a repeat-dose trial in 13 healthy subjects, concomitant administration of erythromycin (a moderate CYP3A4 inhibitor) and salmeterol inhalation aerosol resulted in a 40% increase in salmeterol Cmax at steady state (ratio with and without erythromycin 1.4 [90% CI: 0.96, 2.03], P = 0.12), a 3.6-beat/min increase in heart rate ([95% CI: 0.19, 7.03], P less than 0.04), a 5.8-msec increase in QTc interval ([95% CI: -6.14, 17.77], P = 0.34), and no change in plasma potassium. Five (5) of these 8 subjects had a prolonged QTc interval at baseline. The terminal elimination half-life was about 5.5 hours (1 volunteer only). PROPIONATE FLUTICAS/SALMETEROL 125 µg/25 µg/dose Inhalation buccale boîte de 1 flacon pressurisé de 120 doses Immediate and delayed hypersensitivity reaction (including very rare anaphylactic reaction). Listed in Dosage. No significant differences in ventricular or supraventricular arrhythmias and heart rate were observed among the groups treated with fluticasone propionate and salmeterol inhalation powder 500 mcg/50 mcg, the individual components, or placebo. Animal Data: Subcutaneous administration of tritiated fluticasone propionate at a dose of 10 mcg/kg/day to lactating rats resulted in measurable levels in milk. In a 12-week U.S. trial, fluticasone propionate and salmeterol inhalation powder 100 mcg/50 mcg twice daily was compared with fluticasone propionate inhalation powder 100 mcg twice daily in 203 children with asthma aged 4 to 11 years. If a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. However, these events have occurred in a few patients with less severe asthma as well. To minimize the systemic effects of orally inhaled corticosteroids, including fluticasone propionate and salmeterol inhalation powder, each patient should be titrated to the lowest strength that effectively controls his/her asthma [see Dosage and Administration (2.1)]. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. The clinical relevance of these findings is unknown. The population pharmacokinetic analyses for fluticasone propionate and salmeterol showed no clinically relevant effects of age, gender, race, body weight, body mass index, or percent of predicted FEV1 on apparent clearance and apparent volume of distribution. During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression. Inflammation is also a component in the pathogenesis of COPD. Reduction in asthma symptoms and use of rescue VENTOLIN Inhalation Aerosol and improvement in morning and evening PEF also occurred within the first day of treatment with fluticasone propionate and salmeterol inhalation powder, and continued to improve over the 12 weeks of therapy in both trials. Median changes from baseline in pulse rate and systolic and diastolic blood pressure were similar to those seen with placebo. Fluticasone Propionate: In embryofetal development studies with pregnant rats and mice dosed by the subcutaneous route throughout the period of organogenesis, fluticasone propionate was teratogenic in both species. Inflammation is an important component in the pathogenesis of asthma. Fluticasone propionate is a synthetic trifluorinated corticosteroid with anti-inflammatory activity. Side Effects. Trial 1: Clinical Trial with Fluticasone Propionate and Salmeterol Inhalation Powder 100 mcg/50 mcg: This placebo-controlled, 12-week, U.S. trial compared fluticasone propionate and salmeterol inhalation powder 100 mcg/50 mcg with its individual components, fluticasone propionate 100 mcg and salmeterol 50 mcg. A population pharmacokinetic analysis was performed for fluticasone propionate and salmeterol utilizing data from 9 controlled clinical trials that included 350 subjects with asthma aged 4 to 77 years who received treatment with fluticasone propionate and salmeterol inhalation powder, the combination of HFA-propelled fluticasone propionate and salmeterol inhalation aerosol (ADVAIR HFA), fluticasone propionate inhalation powder (FLOVENT DISKUS), HFA-propelled fluticasone propionate inhalation aerosol (FLOVENT® HFA), or CFC-propelled fluticasone propionate inhalation aerosol. Inhalation by healthy volunteers of a single dose of 4,000 mcg of fluticasone propionate inhalation powder or single doses of 1,760 or 3,520 mcg of fluticasone propionate CFC inhalation aerosol was well tolerated. Effects of treatment with fluticasone propionate and salmeterol inhalation powder 500 mcg/50 mcg, fluticasone propionate 500 mcg, salmeterol 50 mcg, or placebo on BMD was evaluated in a subset of 658 subjects (females and males aged 40 to 80 years) with COPD in the 3-year survival trial. Administration of Seroflo Inhaler is contraindicated in patients with hypersensitivity to the medication. Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. Salmétérol : Cas d'usage. Salmeterol: Salmeterol base is extensively metabolized by hydroxylation, with subsequent elimination predominantly in the feces. Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. Under standardized in vitro test conditions, fluticasone propionate and salmeterol inhalation powder delivers 93 mcg and 233 mcg of fluticasone propionate and 45 mcg of salmeterol base per blister from fluticasone propionate and salmeterol inhalation powder 100 mcg/50 mcg and fluticasone propionate and salmeterol inhalation powder 250 mcg/50 mcg, respectively, when tested at a flow rate of 60 L/min for 2 seconds. if you are having an asthma attack or severe COPD symptoms. The xinafoate moiety has no apparent pharmacologic activity. The volume of distribution averaged 4.2 L/kg. Fluticasone propionate and salmeterol inhalation powder should be used for patients not adequately controlled on a long-term asthma control medication such as an inhaled corticosteroid (ICS) or whose disease warrants initiation of treatment with both an ICS and long-acting beta2-adrenergic agonist (LABA). With preparations containing greater than 100 micrograms fluticasone, a steroid card should be provided. The effect of fluticasone propionate and salmeterol inhalation powder 100 mcg/50 mcg on morning and evening PEF endpoints is shown in Table 5.

Watch your child each time they use the inhaler to be sure that they are using it correctly.Never exhale into the inhaler, take the inhaler apart, or wash the mouthpiece or any part of the inhaler. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although there was no statistical effect on the mean QTc, coadministration of salmeterol and ketoconazole was associated with more frequent increases in QTc duration compared with salmeterol and placebo administration. The maximum recommended dosage is fluticasone propionate and salmeterol inhalation powder 500 mcg/50 mcg twice daily. Contraindications. ICS/LABA did not show a significantly increased risk of a serious asthma-related event compared with ICS based on the pre-specified risk margin (2.7), with an estimated hazard ratio of time to first event of 1.29 (95% CI: 0.73, 2.27). No significant differences across treatments were observed in serum cortisol AUC after 12 weeks of dosing or in 24-hour urinary cortisol excretion after 12 and 28 weeks. Patients with Hepatic and Renal Impairment: Formal pharmacokinetic studies using fluticasone propionate and salmeterol inhalation powder have not been conducted in patients with hepatic or renal impairment. The strip contains a combination of fluticasone propionate 100 or 250 mcg and salmeterol 50 mcg per blister. Transfer of patients from systemic corticosteroid therapy to fluticasone propionate and salmeterol inhalation powder may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions). [See USP Controlled Room Temperature.] Fluticasone + Salmétérol : Tous les traitements et médicaments de la classe thérapeutique Fluticasone + Salmétérol Step 2. The use of fluticasone propionate and salmeterol inhalation powder is contraindicated in the following conditions: Use of LABA as monotherapy (without ICS) for asthma is associated with an increased risk of asthma-related death [see Salmeterol Multicenter Asthma Research Trial (SMART)]. If oropharyngeal candidiasis develops, treat it with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing therapy with fluticasone propionate and salmeterol inhalation powder, but at times therapy with fluticasone propionate and salmeterol inhalation powder may need to be temporarily interrupted under close medical supervision. In vitro studies show salmeterol to be at least 50 times more selective for beta2-adrenoceptors than albuterol. There were no trials conducted to directly compare the efficacy of fluticasone propionate and salmeterol inhalation powder 250 mcg/50 mcg with fluticasone propionate and salmeterol inhalation powder 500 mcg/50 mcg on exacerbations. Similar results were observed in subjects receiving salmeterol 50 mcg plus fluticasone propionate 500 mcg twice daily concurrently with a theophylline product (n = 39) or without theophylline (n = 132). If shortness of breath occurs in the period between doses, an inhaled, short-acting beta2-agonist should be taken for immediate relief. During the trial subjects were permitted usual COPD therapy with the exception of other ICS and long-acting bronchodilators. Use of background ICS was not required in SMART. All treatments were inhalation powders given as 1 inhalation from a dry powder inhaler twice daily, and other maintenance therapies were discontinued. Hold the inhaler in a level, flat position. 100 mcg/50 mcg is supplied as a disposable gray plastic inhaler containing a foil blister strip with 60 blisters. Fertility and reproductive performance were unaffected in male and female rats at subcutaneous doses up to 50 mcg/kg (approximately 0.5 times the MRHDID for adults on a mcg/m2 basis). Statistically significantly fewer subjects receiving fluticasone propionate and salmeterol inhalation powder 250 mcg/50 mcg were withdrawn from this trial for worsening asthma (4%) compared with fluticasone propionate (22%), salmeterol (38%), and placebo (62%). Disease-Associated Maternal and/or Embryofetal Risk: In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal outcomes such as pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. The inhaler is not reusable. Particular care is needed for patients who have been transferred from systemically active corticosteroids to ICS because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available ICS. Fluticasone propionate and salmeterol inhalation powder has not been studied in subjects with acutely deteriorating asthma or COPD. In a 24-month oral and inhalation carcinogenicity study in Sprague Dawley rats, salmeterol caused a dose-related increase in the incidence of mesovarian leiomyomas and ovarian cysts at doses of 680 mcg/kg and above (approximately 66 and 35 times the MRHDID for adults and children, respectively, on a mcg/m2 basis). by: Hikma Pharmaceuticals USA Inc. (floo tik’ a sone proe’ pee oh nate and sal mee’ ter ol). Similar to what was seen in the 1-year trials with fluticasone propionate and salmeterol inhalation powder 250 mcg/50 mcg, the incidence of pneumonia was higher in subjects older than 65 years (18% with fluticasone propionate and salmeterol inhalation powder 500 mcg/50 mcg versus 10% with placebo) compared with subjects younger than 65 years (14% with fluticasone propionate and salmeterol inhalation powder 500 mcg/50 mcg versus 8% with placebo) [see Adverse Reactions (6.2), Use in Specific Populations (8.5)]. It is freely soluble in methanol; slightly soluble in ethanol, chloroform, and isopropanol; and sparingly soluble in water. Fluticasone propionate and salmeterol inhalation powder 250 mcg/50 mcg is also indicated to reduce exacerbations of COPD in patients with a history of exacerbations. The most common events that occurred more frequently were nasopharyngitis, upper respiratory tract infection, nasal congestion, back pain, sinusitis, dizziness, nausea, pneumonia, candidiasis, and dysphonia. Hypersensitivity to fluticasone or any component of the formulation; severe hypersensitivity to milk proteins or lactose (ArmonAir RespiClick, Arnuity Ellipta, Flovent Diskus); primary treatment of status asthmaticus or other acute episodes of asthma requiring intensive measures.Documentation of allergenic cross-reactivity for corticosteroids is limited. In such children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. Generic Name: fluticasone propionate and salmeterol Fluticasone Propionate and Salmeterol Inhalation Powder USP. Some of these patients have clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy. Salmeterol xinafoate is the racemic form of the 1-hydroxy-2-naphthoic acid salt of salmeterol. Hypothalamic-Pituitary-Adrenal Axis Effects: No significant differences across treatments were observed in 24-hour urinary cortisol excretion and, where measured, 24-hour plasma cortisol AUC. Concise Prescribing Info Indications/Uses . Fluticasone + Salmeterol Cipla is only available in two strengths (fluticasone propionate and salmeterol 125/25 microgram and 250/25 microgram). It is not available in a lower strength product containing salmeterol 25 microgram and fluticasone propionate 50 microgram. No formal drug interaction trials have been performed with fluticasone propionate and salmeterol inhalation powder. Salmeterol: In a drug interaction trial in 20 healthy subjects, coadministration of inhaled salmeterol (50 mcg twice daily) and oral ketoconazole (400 mg once daily) for 7 days resulted in greater systemic exposure to salmeterol (AUC increased 16-fold and Cmax increased 1.4-fold). In the repeat- and single-dose trials, there was no evidence of significant drug interaction in systemic exposure between fluticasone propionate and salmeterol when given alone or in combination via a dry powder inhaler. The average duration of exposure was 60 to 79 days in the active treatment groups compared with 42 days in the placebo group. Figure 2: Percent Change in Serial 12-Hour FEV1 in Subjects with Asthma Previously Using Either Inhaled Corticosteroids or Salmeterol (Trial 1), Figure 3: Percent Change in Serial 12-Hour FEV1 in Subjects with Asthma Previously Using Either Inhaled Corticosteroids or Salmeterol (Trial 1). In an embryofetal development study with pregnant mice that received the combination of subcutaneous administration of fluticasone propionate and oral administration of salmeterol at doses of 0/1,400; 40/0; 10/200; 40/1,400; or 150/10,000 mcg/kg/day (as fluticasone propionate/salmeterol) during the period of organogenesis, findings were generally consistent with the individual monoproducts and there was no exacerbation of expected fetal effects. During withdrawal from oral corticosteroids, some patients may experience symptoms of systemically active corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, depression) despite maintenance or even improvement of respiratory function. When choosing the starting dosage strength of fluticasone propionate and salmeterol inhalation powder, consider the patients’ disease severity, based on their previous asthma therapy, including the ICS dosage, as well as the patients’ current control of asthma symptoms and risk of future exacerbation. When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone (see Serious Asthma-Related Events with Inhaled Corticosteroid/Long-acting Beta2-adrenergic Agonists). These trials were not designed to rule out all risk for serious asthma-related events with ICS/LABA compared with ICS. Pregnant women should be closely monitored and medication adjusted as necessary to maintain optimal control of asthma. Serial serum cortisol concentrations were measured across a 12-hour dosing interval. The cardiovascular effects (heart rate, blood pressure) associated with salmeterol inhalation aerosol occur with similar frequency, and are of similar type and severity, as those noted following albuterol administration. Although beta2-adrenoceptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-adrenoceptors are the predominant receptors in the heart, there are also beta2-adrenoceptors in the human heart comprising 10% to 50% of the total beta-adrenoceptors. Following administration of fluticasone propionate and salmeterol inhalation powder to healthy adult subjects, peak plasma concentrations of salmeterol were achieved in about 5 minutes. When beginning treatment with fluticasone propionate and salmeterol inhalation powder, patients who have been taking oral or inhaled, short-acting beta2-agonists on a regular basis (e.g., 4 times a day) should be instructed to discontinue the regular use of these drugs. Fluticasone propionate and salmeterol inhalation powder contains both fluticasone propionate and salmeterol; therefore, the risks associated with overdosage for the individual components described below apply to fluticasone propionate and salmeterol inhalation powder. There are insufficient data on the use of fluticasone propionate and salmeterol inhalation powder or individual monoproducts, fluticasone propionate and salmeterol xinafoate, in pregnant women. Follow the instructions below so you will not accidentally waste a dose: The counter on top of the inhaler shows you how many doses are left. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. The subjects had a mean pre-bronchodilator FEV1 of 41% and 20% reversibility at trial entry. salmeterol reported an adverse event. Animal Data: Fluticasone Propionate and Salmeterol: In an embryofetal development study with pregnant rats that received the combination of subcutaneous administration of fluticasone propionate and oral administration of salmeterol at doses of 0/1,000; 30/0; 10/100; 30/1,000; and 100/10,000 mcg/kg/day (as fluticasone propionate/salmeterol) during the period of organogenesis, findings were generally consistent with the individual monoproducts and there was no exacerbation of expected fetal effects. The values for 24-hour urinary cortisol excretion at trial entry and after 12 weeks of treatment were similar within each treatment group. In this trial, 70% of the subjects treated with fluticasone propionate and salmeterol inhalation powder reported an adverse reaction compared with 64% on placebo. Healthy Subjects: Cardiovascular Effects: Since systemic pharmacodynamic effects of salmeterol are not normally seen at the therapeutic dose, higher doses were used to produce measurable effects. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist. If asthma symptoms arise in the period between doses, an inhaled, short-acting beta2-agonist should be taken for immediate relief. Adult : Inhalation Asthma Per powd inhalation dose contains salmeterol 50 mcg and fluticasone propionate 100/250/500 mcg: 1 inhalation twice daily. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for fluticasone propionate and salmeterol inhalation powder and any potential adverse effects on the breastfed child from fluticasone propionate and salmeterol inhalation powder or from the underlying maternal condition. And 20 % reversibility at trial entry geometric mean AUC was 325 pg•h/mL ( 90 CI. 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