Skip to main content
SpringerLink
Log in

Inhaled Salmeterol/Fluticasone Propionate Combination

A Review of its Use in Persistent Asthma

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Abstract

The long-acting β2-agonist salmeterol and the corticosteroid fluticasone propionate are available as a combination inhalation device for the treatment of persistent asthma.

Well designed studies in adults, adolescents and children aged ≥4 years, demonstrate that combined salmeterol/fluticasone propionate 50/100, 50/250 and 50/500μg administered via a dry powder inhaler (DPI) is clinically equivalent to concurrent delivery of the same dosages of the 2 drugs via separate DPIs.

In adults and adolescents, combined salmeterol/fluticasone 50/100 and 50/250μg twice daily produced rapid improvements in lung function that were consistently greater than those in patients receiving monotherapy twice daily salmeterol 50μg, fluticasone propionate 100 or 250μg or placebo in 2 well designed studies. Recipients of the combination had a significantly greater probability of completing 12 weeks of treatment than patients receiving monotherapy or placebo. The combination also produced significant improvements between baseline and end-point in all secondary outcome variables (morning and evening peak expiratory flow, daytime symptom scores, days and nights without asthma symptoms and requirements for as-needed β-agonists) and health-related quality of life (QOL). Combination therapy was superior to monotherapy with salmeterol and placebo for all outcomes in both studies, and was superior to fluticasone propionate 100μg for all but 1 outcome (nights without awakenings) in 1 study. Similar results were obtained in patients who had previously been using short acting β2-agonists alone.

Combined twice daily salmeterol/fluticasone propionate 50/100 and 50/250μg produced greater improvements in lung function than inhaled budesonide at higher dosages than fluticasone propionate in the combination.

Combined salmeterol/fluticasone propionate 50/250μg produced similar improvements in lung function to concurrent budesonide 800μg plus formoterol 12μg when given twice daily for 12 weeks. In another 12-week trial, combined salmeterol/fluticasone propionate 50/100μg was more effective than oral montelukast 10 mg/day plus fluticasone propionate 100μg twice daily in patients with suboptimally controlled asthma.

Salmeterol/fluticasone is more cost effective than monotherapy with fluticasone propionate or budesonide.

The most frequent adverse events associated with salmeterol/fluticasone propionate are headache, throat irritation, hoarseness and candidiasis.

Conclusion: Combined salmeterol/fluticasone propionate is as effective as the 2 drugs given concurrently via separate inhalers and significantly more effective than either drug given alone at the same nominal dosage. The combination is also significantly more effective than montelukast plus fluticasone propionate or monotherapy with inhaled budesonide. Furthermore, the combination is more cost effective than inhaled corticosteroid monotherapy.

Pharmacodynamic Properties

Salmeterol, a long-acting inhaled β2-agonist bronchodilator, protects against bronchoconstriction and may have some anti-inflammatory properties.

The inhaled corticosteroid fluticasone propionate inhibits eosinophil activation and the subsequent release of inflammatory mediators and may also reduce bronchial hyperresponsiveness in patients with asthma.

The systemic pharmacodynamic effects of salmeterol and fluticasone propionate administered together are similar to those observed when the drugs are given alone or concurrently. No evidence of interaction between the 2 drugs was observed in single and multiple dose studies of the effects of fluticasone propionate on 24-hour urinary cortisol excretion versus equivalent doses of fluticasone propionate alone. When salmeterol/fluticasone propionate 50/100μg was compared with placebo, no significant effect on 24-hour urinary cortisol excretion was detected.

Similarly, in a cumulative dose study comparing the combination with equivalent doses of salmeterol alone, most pharmacodynamic responses to salmeterol were unaffected by the presence of fluticasone propionate.

In children aged 4 to 11 years who had previously been treated with inhaled corticosteroids, geometric mean morning serum cortisol levels increased during 12 weeks of twice daily treatment with salmeterol plus fluticasone propionate 50/100μg. However, no significant differences in the frequency of abnormal plasma cortisol values were detected in adults with persistent asthma during treatment with combined salmeterol/fluticasone propionate 50/250μg twice daily, either drug alone or placebo in a multicentre randomised double-blind study.

Pharmacokinetic Properties

Salmeterol is not detectable in plasma after administration by inhalation and there is no evidence that concomitant administration of fluticasone propionate alters the systemic availability of salmeterol.

Studies comparing fluticasone propionate monotherapy with each strength of salmeterol/fluticasone propionate suggest that the systemic availability of fluticasone propionate is not increased when salmeterol is given concomitantly.

Both salmeterol and fluticasone propionate are metabolised by cytochrome P450 3A4. Renal clearance accounts for <0.02% of the total clearance of fluticasone propionate and for <5% of salmeterol.

Therapeutic Efficacy

The therapeutic efficacy of combined salmeterol and fluticasone propionate in patients with persistent asthma has been established in large multicentre randomised double-blind parallel-group studies. With the exception of 1 study that enrolled patients with a history of recent salmeterol treatment alone, and 1 trial that recruited patients who had used short acting β2-agonists only, eligible patients in all studies had symptomatic asthma despite ongoing treatment with inhaled corticosteroids. The dose of salmeterol (50 μg/actuation) was constant in all studies regardless of whether patients received the drug alone, or in combination or concurrently with fluticasone propionate. The dose of fluticasone propionate varied (100, 250 or 500 μg/actuation). All inhaled products in these studies were administered as 1 actuation twice daily.

Studies in adults and adolescents aged ≥12 years and in children aged 4 to 11 years, have demonstrated the clinical efficacy of combined delivery of salmeterol/fluticasone propionate 50/100, 50/250 and 50/500μg twice daily via the Diskus dry powder inhaler (DPI) to be equivalent to that of concurrent delivery of the same dosages of the 2 drugs via separate Diskus DPIs as assessed by lung function and asthma symptom scores.

Combined salmeterol/fluticasone propionate has recently been formulated as a chlorofluorocarbon (CFC)-free pressurised metered dose inhaler (MDI). Two studies have demonstrated equivalency of this formulation with the Diskus DPI. Improvements in mean morning peak expiratory flow (PEF) were similar after 12 weeks of treatment with combined salmeterol/fluticasone propionate 50/100 or 50/500 delivered via the DPI or MDI.

The efficacy of combined salmeterol/fluticasone propionate was subsequently compared with that of the individual components in 3 well designed US studies which enrolled adults and adolescents aged ≥12 years. Combined salmeterol/fluticasone 50/100 or 50/250μg produced rapid and consistent improvements in lung function that were maintained throughout two 12-week studies in patients previously treated with inhaled corticosteroids or salmeterol. The combination had a significantly faster onset of effect on day 1 of the studies than placebo or fluticasone propionate. Improvements in forced expiratory volume in 1 second (FEV1) between baseline and end-point were consistent between studies and were significantly greater in those treated twice daily with combined salmeterol/fluticasone propionate 50/100μg or 50/250μg than either salmeterol 50μg or fluticasone propionate 100 or 250μg. Improvements in FEV1 were similar regardless of baseline corticosteroid therapy or whether patients were using inhaled corticosteroids or salmeterol alone prior to enrolment.

The probability of being withdrawn from either study because of asthma exacerbations was significantly lower in patients randomised to combination therapy (≤4%) than in each of the other groups. Placebo recipients had the highest rates of withdrawal for worsening asthma (≥49%) followed by salmeterol-treated patients (≥35%).

Treatment with combined salmeterol/fluticasone propionate produced significant improvements between baseline and end-point in all secondary outcome variables (morning and evening PEF), daytime symptom scores, days and nights without asthma symptoms and requirements for as-needed β-agonists) and health-related quality of life (QOL). Combination therapy was superior to monotherapy with salmeterol and placebo for all outcomes in both studies, and was superior to fluticasone propionate for all but 1 outcome (nights without awakenings) in the study that used the lower dosage (50/100μg). Clinically significant differences in total Asthma Quality of Life Questionnaire (AQLQ) scores (≥0.5 units), were obtained in patients treated with the combination compared with placebo (1.3 units) and salmeterol 50μg (≥1 units) but not fluticasone propionate 100 or 250μg.

Similar results were obtained in patients who had previously been using short acting β2-agonists alone. Recipients of combined salmeterol/fluticasone propionate 50/100μg experienced significantly greater improvements in the area under the FEV1 curve (AUC0-12h FEV1), mean morning and evening PEF, and FEV1 than did patients treated with salmeterol or fluticasone propionate alone after 12 weeks of treatment.

A further series of randomised double-blind parallel-group studies have compared combined salmeterol/fluticasone propionate with inhaled budesonide or concurrent budesonide plus formoterol. Salmeterol/fluticasone propionate 50/250μg had a rapid onset of action, such that, throughout the first week of treatment with the combination, mean morning PEF was significantly greater and the proportion of patients with no symptoms or no need for as-needed β2-agonists was significantly lower than in patients randomised to inhaled budesonide 800μg twice daily. These trends were maintained throughout the 24-week study. The combination also produced improvements in QOL scores that were clinically significant compared with baseline and statistically significant compared with scores in budesonide recipients after 24 weeks.

Improvements in mean morning and evening PEF were significantly greater among patients with persistent asthma randomised to combined salmeterol/fluticasone propionate 50/100μg twice daily than budesonide 400μg twice daily in a further 12-week study.

Similar improvements in lung function were obtained with combined salmeterol/fluticasone propionate 50/250μg and concurrent budesonide 800μg plus formoterol 12μg twice daily in a 12-week randomised double-blind multi-centre study.

Combined salmeterol/fluticasone propionate 50/100μg was more effective than the addition of oral montelukast 10 mg/day to fluticasone propionate 100μg twice daily in patients aged ≥15 years with suboptimally controlled asthma according to the results of a 12-week study. Mean morning PEF, the primary efficacy variable in the study, was significantly greater among patients treated with the combination on each day during the first week of treatment and in each week of the study thereafter. Similar trends were evident for improvements in mean evening PEF, clinic FEV1, and reductions in as-needed β2-agonist usage, all of which were significantly greater in patients treated with combined salmeterol/fluticasone propionate than montelukast plus fluticasone propionate. Asthma exacerbations also occurred in significantly fewer patients treated with the combination than montelukast plus fluticasone propionate (2 vs 6%). The mean change in total Daytime Asthma Symptom Scores was similar in patients in both treatment groups.

Pharmacoeconomic Considerations

Data from 3 studies comparing salmeterol/fluticasone propionate and fluticasone propionate have been subjected to cost-effectiveness analyses from the perspective of the Swedish healthcare system [valued in Swedish Kronor (SEK 1998)].

In all 3 studies, the total costs of asthma management were higher in the salmeterol/fluticasone propionate group than in the corresponding fluticasone propionate group. However, the cost per successfully-treated week was lower for salmeterol/fluticasone propionate across all 3 studies. The incremental cost effectiveness ratios varied from SEK12.6 ($US1.53) per additional successfully-treated week with salmeterol/fluticasone propionate 50/250μg to SEK192.1 ($US23.31) per additional successfully-treated week with salmeterol/fluticasone propionate 50/500μg.

A 24-week study comparing salmeterol/fluticasone propionate with budesonide has been subjected to cost-effectiveness analyses from Swedish, German and UK perspectives. Each analysis found salmeterol/fluticasone propionate to be more cost-effective than budesonide despite higher acquisition costs for the combination.

Tolerability

As salmeterol/fluticasone propionate is a combination of 2 drugs, the type and severity of adverse events associated with each component drug may be expected in patients receiving the combination product. There is no evidence, however, of additional adverse events following concurrent administration of the 2 drugs.

According to overall analysis of tolerability data from well designed studies the most frequent adverse events associated with salmeterol/fluticasone propionate are headache (incidence 2 to 5%), throat irritation (1 to 4%), hoarseness (≤4%) and oral candidiasis (1 to 4%).

The overall frequency of adverse events was similar between treatment groups in a comparative study in which patients received combined salmeterol/fluticasone propionate 50/250μg or budesonide 800μg twice daily for 24 weeks.

Withdrawal rates among patients treated with combined salmeterol/fluticasone propionate ranged from 0 to 10% and were similar to those in other treatment groups in the various studies.

Dosage and Administration

In the US, combined salmeterol/fluticasone propionate is indicated for long term maintenance treatment of asthma in patients aged ≥12 years. The recommended starting dosage is based on patients’ current asthma therapy. Twice daily salmeterol/fluticasone propionate 100/50μg via DPI is the recommended initial dosage in patients not currently receiving inhaled corticosteroids.

In the UK, combined salmeterol/fluticasone propionate is indicated in the treatment of asthma where use of the combination of a long-acting inhaled β2-agonist and inhaled corticosteroid is appropriate. This corresponds to ‘Step 3’ in the British Guidelines on Asthma Management.

The recommended dosages of salmeterol/fluticasone propionate in patients aged ≥12 years is 1 inhalation twice daily of the DPI (each inhalation contains 50μg salmeterol and either 100, 250 or 500μg fluticasone propionate) or 2 inhalations twice daily of the MDI (each inhalation contains salmeterol/fluticasone propionate 25/50μg, 25/125μg, or 25/250μg). The dosage of fluticasone propionate should be selected according to the severity of asthma in individual patients. In children aged <12 and ≥4 years, the recommended dosage is 1 inhalation twice daily of the lowest strength of the DPI (salmeterol/fluticasone propionate 50/100μg). No data are available regarding use of salmeterol/fluticasone propionate in children aged <4 years.

Salmeterol/fluticasone propionate should not be used to treat acute asthma symptoms for which a short acting β2-agonist bronchodilator is required. Patients should be advised to have their relief medication available at all times.

No dosage adjustment is required in the elderly or in patients with renal impairment. Patients with hepatic disease should be closely monitored during treatment with the combination.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I
Table II
Table III
Fig. 2
Table IV
Fig. 3
Fig. 4
Table V
Table VI
Fig. 5
Table VII
Table VIII

Similar content being viewed by others

References

  1. Dahl R. Salmeterol and fluticasone propionate in the treatment of asthma symptoms. Eur Resp Rev 1997 Aug; 7: 338–43

    Google Scholar 

  2. Jack D. The use of inhaled β2-adrenergic bronchodilators and anti-inflammatory steroids in asthma. J of Pharm Med 1996; 6(1-2): 5–16

    Google Scholar 

  3. Chung KF. tary role of glucocorticosteroids and long-acting β-adrenergic agonists. Allergy 1998; 53 Suppl. 42: 7–13

    Article  PubMed  CAS  Google Scholar 

  4. Eickelberg O, Roth M, Lörx R, et al. Ligand-independent activation of the glucocorticoid receptor by β2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells. J Biol Chem 1999 Jan; 274(2): 1005–10

    Article  PubMed  CAS  Google Scholar 

  5. Chrystyn H. The Diskus inhaler: a review of its pharmaceutical and clinical performance. Clin Drug Invest 1999; 18(4): 287–96

    Article  Google Scholar 

  6. Ashurst IC, Gordon P. Consistent dose delivery from a new metered dose inhaler containing a combination of salmeterol and fluticasone propionate in HFA134A [abstract no. P2295]. Eur Respir J 1999; 14 Suppl. 30: 341S

    Google Scholar 

  7. British National Formulary. No. 40. London: The Pharmaceutical Press, 2000: 772

  8. National Asthma Education and Prevention Program. Expert panel report 2: guidelines for the diagnosis and management of asthma. National Institutes of Health. Bethesda, MD. National Heart, Lung, and Blood Institute, 1997 Jul: 153. NIH Publication no. 97-4051

  9. British Thoracic Society, National Asthma Campaign, Royal College of Physicians of London, et al. The British Guidelines on asthma management: 1995 review and position statement. Thorax 1997 Feb; 52 Suppl. 1: S1–21

    Article  Google Scholar 

  10. Spencer CM, Jarvis B. Salmeterol/fluticasone propionate combination. Drugs 1999 Jun; 57: 933–40

    Article  PubMed  CAS  Google Scholar 

  11. Holliday SM, Faulds D, Sorkin EM. Inhaled fluticasone propionate: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in asthma. Drugs 1994 Feb; 47: 318–31

    Article  PubMed  CAS  Google Scholar 

  12. Jarvis B, Faulds D. Inhaled fluticasone propionate: a review of its therapeutic efficacy at dosages <500 μg/day in adults and adolescents with mild to moderate asthma. Drugs 1999 May; 57: 769–803

    Article  PubMed  CAS  Google Scholar 

  13. Brogden RN, Faulds D. Salmeterol xinafoate: a review of its pharmacological properties and therapeutic potential in reversible obstructive airways disease. Drugs 1991; 42: 895–912

    Article  PubMed  CAS  Google Scholar 

  14. Adkins JC, McTavish D. Salmeterol: a review of its pharmacological properties and clinical efficacy in the management of children with asthma. Drugs 1997 Aug; 54: 331–54

    Article  PubMed  CAS  Google Scholar 

  15. Johnson M. Development of fluticasone propionate and comparison with other inhaled corticosteroids. J Allergy Clin Immunol 1998 Apr; 101 (Pt 2 Suppl. 1): S434–439

    Article  PubMed  CAS  Google Scholar 

  16. Man CY, Kirby SM, McRae J, et al. Systemic pharmacodynamic effects of salmeterol in the salmeterol/FP combination Diskus inhaler [abstract no. P1073]. Eur Respir J 1996 Sep; 9 Suppl. 23: 164s

    Google Scholar 

  17. Van den Berg NJ, Ossip MS, Hederos CA, et al. Salmeterol/fluticasone propionate (50/100 μg) in combination in a Diskus™ inhaler (Seretide™) is effective and safe in children with asthma. Pediatr Pulmonol 2000; 30: 97–105

    Article  PubMed  Google Scholar 

  18. Shapiro G, Lumry W, Wolfe J, et al. Combined salmeterol 50 μg and fluticasone propionate 250 μg in the Diskus device for the treatment of asthma. Am J Respir Crit Care Med 2000 Feb; 161: 527–34

    PubMed  CAS  Google Scholar 

  19. Thorsson L, Dahlström K, Edsbäcker S, et al. Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects. Br J Clin Pharmacol 1997; 43: 155–61

    Article  PubMed  CAS  Google Scholar 

  20. Esmailpour N, Högger P, Rabe KF, et al. Distribution of inhaled fluticasone propionate between human lung tissue and serum in vivo. EurRespir J 1997; 10: 1496–9

    CAS  Google Scholar 

  21. Glaxo Wellcome UK Ltd. Salmeterol/fluticasone propionate prescribing information. Uxbridge: Glaxo; 1999 Jul 27: 7

    Google Scholar 

  22. Aubier M, Pieters WR, Schlösser NJJ, et al. Salmeterol/fluticasone propionate (50/500 μg) in combination in a Diskus inhaler (Seretide) is effective and safe in the treatment of steroid-dependent asthma. Respir Med 1999 Dec; 93: 876–84

    Article  PubMed  CAS  Google Scholar 

  23. Bateman ED, Britton M, Carrillo J, et al. Salmeterol/fluticasone combination inhaler: a new, effective and well tolerated treatment for asthma. Clin Drug Invest 1998 Sep; 16: 193–201

    Article  CAS  Google Scholar 

  24. Chapman KR, Ringdal N, Backer V, et al. Salmeterol and fluticasone propionate (50/250 μg) administered via combination Diskus inhaler: as effective as when given via separate Diskus inhalers. Can Respir J 1999; 6(1): 45–51

    PubMed  CAS  Google Scholar 

  25. Bateman ED, Beasley R, Silins V, et al. Comparison of salmeterol/fluticasone propionate combination 50/100 bid delivered via metered dose inhaler or Diskus in patients with reversible airways obstruction [abstract]. Am J Respir Crit Care Med 2000 Mar; 161(3): A197

    Google Scholar 

  26. van Noord JA, Lill H, Carillo T, et al. Comparative effectiveness of salmeterol/fluticasone propionate combination 50/500 bid delivered via metered dose inhaler or Diskus in patients with reversible airways obstruction [abstract no. 45]. J Allergy Clin Immunol 2000 Jan; 104 (1 Pt 2): S15

    Google Scholar 

  27. Kavuru M, Melamed J, Gross G, et al. Salmeterol and fluticasone propionate combined in a new powder inhalation device for the treatment of asthma: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 2000 Jun; 105 (Pt 1): 1108–16

    Article  PubMed  CAS  Google Scholar 

  28. Nelson H, Chervinsky P, Greos L, et al. The salmeterol/fluticasone propionate combination product improves asthma control compared with the individual products in asthmatics treated with short-acting β2-agonists alone [abstract]. Am J Respir Crit Care Med 2000 Mar; 161(3): A196

    Google Scholar 

  29. Jenkins C, Woolcock AJ, Saarelainen P, et al. Salmeterol/fluticasone propionate combination therapy 50/250 μg twice daily is more effective than budesonide 800 μg twice daily in treating moderate to severe asthma. Respir Med 2000; 94: 715–23

    Article  PubMed  CAS  Google Scholar 

  30. Juniper EF, Jenkins C, Price MJ, et al. Quality of life of asthma patients treated with salmeterol/fluticasone propionate combination product and budesonide [abstract no. P2460]. Annual Congress European Respiratory Society; 1999 Oct 9–13, Madrid

  31. Johansson G, Mclvor RA, Purello FDA, et al. Salmeterol/fluticasone propionate combination dry powder inhaler (50/100 μg bid) is more effective than budesonide (400 μg bid) in mild to moderate asthma [abstract no. P162]. Eur Respir J 1998; 12 Suppl. 29: 20s

    Google Scholar 

  32. Ringdal N, Chuchalin AG, Chovan L, et al. A comparison of Advair/Seretide (salmeterol 50 μg/fluticasone propionate 250 μg bid) with formoterol 12 μg + budesonide 800 μg bid in moderate-severe asthma [abstract]. Am J Respir Crit Care Med 2000 Mar; 161(3): A196

    Google Scholar 

  33. Nelson HS, Busse WW, Kerwin E, et al. Fluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast. J Allergy Clin Immunol. In press

  34. Nelson HS, Baitinger L, Scott C, et al. Salmeterol/fluticasone propionate (50/100(Ig dose) non-CFC metered dose inhaler is safe and effective in patients with asthma using short-acting β2-agonists alone [abstract no. P508]. Eur Respir J 2000; 16 Suppl. 31: 53s

    Google Scholar 

  35. Lumry W, Windom H, Mendelson L, et al. The salmeterol/fluticasone propionate (50/250mcg) dry powder combination Diskus has a faster onset of effect compared with salmeterol or fluticasone propionate in patients with asthma [abstract no. 501]. J Allergy Clin Immunol 1999 Jan; 103 (1 Pt 2): S132

    Google Scholar 

  36. Nathan R, LaForce C, Mitchell D, et al. The salmeterol/fluticasone propionate combination (50/100mcg) via Diskus has a rapid onset of effect in asthma patients on salmeterol or inhaled corticosteroids. Presented at the American Thoracic Society Meeting; 1999 Apr 23–28; San Diego, 1999

  37. Pearlman D, Baitinger L, Woodring A, et al. Salmeterol 50mcg/fluticasone propionate 250mcg Diskus combination product demonstrates improvements in lung function regardless of baseline corticosteroid therapy [abstract]. Am J Respir Crit Care Med 2000 Mar; 161 (3 Pt 2): A196

    Google Scholar 

  38. LaForce C, Woodring A, Baitinger L, et al. Salmeterol 50mcg/fluticasone propionate lOOmcg Diskus combination product demonstrates improvements in lung function regardless of baseline corticosteroid therapy [abstract no. 35]. J Allergy Clin Immunol 2000 Jan; 105 (1 Pt 2): S12

    Article  Google Scholar 

  39. Wolfe J, Bell T, Raphael G, et al. Efficacy of the salmeterol/fluticasone propionate dry powder combination product in the Diskus: a stratified study in patients on salmeterol alone or inhaled corticosteroids [abstract no. 879]. J Allergy Clin Immunol 1999 Jan; 103 (1 Pt 2): S228

    Google Scholar 

  40. Sheffer AL, Bartal M, Bousquet J, et al. Global strategy for asthma management and prevention NHLBI/WHO workshop. NHLBI/WHO Workshop Report based on a March 1993 meeting. Bethesda, MD. National Heart, Lung, and Blood Institute, 1995 Jan. NTH Publication no. 95-3659

  41. Reese PR, Mahajan P, Woodring A. Salmeterol/fluticasone propionate combination product improves quality of life in asthma patients [abstract no. P0325]. Eur Respir J 1998 Sep; 12 Suppl. 28: 35s

    Google Scholar 

  42. Reese PR, Mather DB, Mahajan P, et al. Combination of salmeterol/fluticasone propionate via Diskus improves quality of life in asthma patients. J Allergy Clin Immunol 1999 Jan; 103 Pt (Pt 2): 69

    Google Scholar 

  43. Jenkins C, Wolcock A, Saarelainen P, et al. Advair/Seretide (salmeterol 50mcg/fluticasone propionate 250 mcg bid) compared with budesonide (800 mcg bid) during the first week of treatment of moderate asthma [bstract no. 493]. J Allergy Clin Immunol 2000 Jan; 105 (1 Pt 2): S161

    Article  Google Scholar 

  44. Pieters WR, Lundbäck B, Johansson G, et al. Cost-effectiveness analyses of salmeterol/fluticasone propionate combination product and fluticasone propionate in patients with asthma II: Study methodologies. PharmacoEconomics 1999; 16 Suppl. 2: 9–14

    Article  CAS  Google Scholar 

  45. Lundbäck B, Pieters WR, Johansson G, et al. Cost-effectiveness analyses of salmeterol/fluticasone propionate combination product and fluticasone propionate in patients with asthma I: introduction and overview. PharmacoEconomics 1999; 16 Suppl. 2: 1–8

    Article  Google Scholar 

  46. Johansson G, Price MJ, Sondhi S. Cost-effectiveness analysis of salmeterol/fluticasone propionate 50/100 μg vs fluticasone propionate 100 μg in adults and adolescents with asthma III: results. PharmacoEconomics 1999; 16 Suppl. 2: 15–21

    Article  CAS  Google Scholar 

  47. Palmqvist M, Price MJ, Sondhi S. Cost-effectiveness analysis of salmeterol/fluticasone propionate 50/250 μg vs fluticasone propionate 250 μg in adults and adolescents with asthma IV: results. PharmacoEconomics 1999; 16 Suppl. 2: 23–8

    Article  CAS  Google Scholar 

  48. Pieters WR, Lundbäck B, Sondhi S, et al. Cost-effectiveness analysis of salmeterol/fluticasone propionate 50/500 μg vs fluticasone propionate 500 μg in patients with corticosteroid-dependent asthma V: results. PharmacoEconomics 1999; 16 Suppl. 2: 29–34

    Article  CAS  Google Scholar 

  49. Lundbäck B, Jenkins C, Price MJ, et al. Cost-effectiveness of salmeterol/fluticasone propionate combination product 50/250 μg twice daily and budesonide 800 μg twice daily in the treatment of adults and adolescents with asthma. Respir Med 2000; 94: 724–32

    Article  PubMed  Google Scholar 

  50. Becker I, Kielborn A, Price MJ, et al. Cost-effectiveness of salmeterol/fluticasone combination product and budesonide in asthma patients in Germany [abstract no. P854]. Annual Congress European Respiratory Society; 1999, Oct 9–13, Madrid

  51. Lloyd A, Browning D, Shrewsbury S. Cost-effectiveness of salmeterol/fluticasone combination product and budesonide bd in the United Kingdom (asthma) [abstract]. Am J Respir Crit Care Med 2000 Mar; 161(3): A196

    Google Scholar 

  52. Mann RD, Kubota K, Pearce G, et al. Salmeterol: a study by prescription-event monitoring in a UK cohort of 15,407 patients. J Clin Epidemiol 1996 Feb; 49: 247–50

    Article  PubMed  CAS  Google Scholar 

  53. Glaxo Wellcome Inc. Advair Diskus (fluticasone propionate and salmeterol) product information. Glaxo Wellcome Inc. Research: Triangle Park, NC; 2000 Aug: 30

  54. Greening AP, Ind PW, Northfield M, et al. Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Allen & Hanburys Limited UK Study Group. Lancet 1994 Jul 23; 344(8917): 219–24

    Article  PubMed  CAS  Google Scholar 

  55. Woolcock A, Lundback B, Ringdal N, et al. Comparison of addition of salmeterol to inhaled steroids with doubling of the dose of inhlaed steroids. Am J Respir Crit Care Med 1996 May; 153(5): 1481–8

    PubMed  CAS  Google Scholar 

  56. Baraniuk J, Murray JJ, Nathan RA, et al. Fluticasone alone or in combination with salmeterol vs triamcinolone in asthma. Chest 1999 Sep; 116: 625–32

    Article  PubMed  CAS  Google Scholar 

  57. Condemi JJ, Goldstein S, Kalberg C, et al. The addition of salmeterol to fluticasone propionate versus increasing the dose of fluticasone propionate in patients with persistent asthma. Salmeterol Study Group. Ann Allergy Asthma Immunol 1999 Apr; 82: 383–9

    Article  PubMed  CAS  Google Scholar 

  58. Pearlman DS, Stricker W, Weinstein S, et al. Inhaled salmeterol and fluticasone: a study comparing monotherapy and combination therapy in asthma [see comments]. Ann Allergy Asthma Immunol 1999 Mar; 82: 257–65

    Article  PubMed  CAS  Google Scholar 

  59. Murray JJ, Church NL, Anderson WH, et al. Concurrent use of salmeterol with inhaled corticosteroids is more effective than inhaled corticosteroid dose increases. All AstProc 1999 May–Jun; 20(3): 173–80

    Article  CAS  Google Scholar 

  60. Kelsen SG, Church NL, Gillman SA, et al. Salmeterol added to inhaled corticosteroid therapy is superior to doubling the dose of inhaled corticosteroids: a randomized clinical trial. J Asthma 1999 Dec; 36 (8703–715)

    Google Scholar 

  61. Shrewsbury S, Pyke S, Britton M. Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA). BMJ 2000 May 20; 320: 1368–73

    Article  PubMed  CAS  Google Scholar 

  62. Nielsen LP, Pedersen B, Faurschou P, et al. Salmeterol reduces the need for inhaled corticosteroid in steroid dependent asthmatics. Respir Med 1999 Dec; 93(12): 863–8

    Article  PubMed  CAS  Google Scholar 

  63. Busse W, Nelson H, Wolfe J, et al. Comparison of inhaled salmeterol and oral zafirlukast in patients with asthma. J Allergy Clin Immunol 1999 Jun; 103(6): 1075–80

    Article  PubMed  CAS  Google Scholar 

  64. Chapman KR, Walker L, Cluley S, et al. Improving patient compliance with asthma therapy. Respir Med 2000 Jan; 94(1): 2–9

    Article  PubMed  CAS  Google Scholar 

  65. Cochrane GM. Compliance in asthma. Eur Resp Rev 1998; 8(56): 239–42

    Google Scholar 

  66. Cochrane GM, Horne R, Chanez P. Compliance in asthma. Respir Med 1999; 93: 763–9

    Article  PubMed  CAS  Google Scholar 

  67. Clark N, Jones P, Keller S, et al. Patient factors and compliance with asthma therapy. Respir Med 1999; 93: 856–62

    Article  PubMed  CAS  Google Scholar 

  68. Chapman KR. Effect of the inhaled route of administration on compliance in asthma. Eur Resp Rev 1998; 8(56): 275–9

    Google Scholar 

  69. Jarvis MJ. Psychological profile of compiler versus noncomplier. Eur Resp Rev 1998; 8(56): 250–4

    Google Scholar 

  70. Hyland ME. Types of noncompliance. Eur Resp Rev 1998; 8(56): 255–9

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Anthony Markham & Blair Jarvis

Authors
  1. Anthony Markham
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Blair Jarvis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Blair Jarvis.

Additional information

Various sections of the manuscript reviewed by: M. Aubier, Unité de Pneumologie, Hospital Bichat, Paris, France; E. Bateman, Respiratory Clinic, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa; W.E. Berger, Southern California Research Center, Mission Viejo, California, USA; M. Britton, St Peters Hospital, Chertsey, Surrey, England; R. Dahl, Department of Respiratory Diseases, Aarhus University Hospital, Aarhus C, Denmark.

Data Selection

Sources: Medical literature published in any language since 1966 on Salmeterol/Fluticasone-propionate, identified using Medline and EMBASE, supplemented by AdisBase (a proprietary database of Adis International, Auckland, New Zealand). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: Medline search terms were ‘Salmeterol Fluticasone’. EMBASE search terms were ‘Salmeterol Fluticasone’. AdisBase search terms were ‘Salmeterol/Fluticasone-propionate’. Searches were last updated 9 Oct 2000.

Selection: Studies in patients with persistent asthma who received combined salmeterol/fluticasone propionate. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: asthma, fluticasone propionate, salmeterol, salmeterol/fluticasone propionate, pharmacodynamics, pharmacokinetics, therapeutic use.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Markham, A., Jarvis, B. Inhaled Salmeterol/Fluticasone Propionate Combination. Drugs 60, 1207–1233 (2000). https://doi.org/10.2165/00003495-200060050-00012

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200060050-00012

Keywords

Search

Navigation