Information intended for healthcare professionals only.

This formulary decision guide was developed from content provided by Boehringer Ingelheim Limited in a format developed by Guidelines in Practice. Boehringer Ingelheim Limited reviewed the content for compliance with the ABPI code of practice.

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Key points

Spiriva Respimat FDG

  • Spiriva® Respimat® (tiotropium) is a long-acting muscarinic antagonist (LAMA) indicated as add-on maintenance bronchodilator treatment in patients aged 6 years and older with severe asthma who experienced one or more severe asthma exacerbations in the preceding year1
  • The Respimat® Soft Mist™ inhaler is suitable for patients aged 6 years and older2
  • Spiriva Respimat has a 30-day acquisition cost of £23.00 and is the only LAMA licensed in asthma3

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Drug name

Spiriva® Respimat® (tiotropium)

Indications

  • Spiriva Respimat is indicated as add-on maintenance bronchodilator treatment in patients aged 6 years and older with severe asthma who experienced one or more severe exacerbations in the preceding year1
  • Refer to the Summary of Product Characteristics for full details of indications and posology.1

Dosage

  • The recommended dose is 5 μg tiotropium given as two puffs once daily, at the same time of the day1
  • For patients with severe asthma, use in addition to inhaled corticosteroids (ICS) and at least one controller
    • adults: ICS (≥800 μg budesonide/day or equivalent) and at least one controller
    • adolescents (12–17 years): ICS (>800–1600 μg budesonide/day or equivalent) and at least one controller, or ICS (400–800 μg budesonide/day or equivalent) with two controllers
    • children (6–11 years): ICS (>400 μg budesonide/day or equivalent) and one controller, or ICS (200–400 μg budesonide/day or equivalent) with two controllers.1

Device

  • The Respimat® Soft Mist™ inhaler generates a slow-moving aerosol with a high fine-particle fraction4
  • In a single-centre study involving 92 children aged 6–12 years, including healthy volunteers and asthmatics, 95% of these children performed a successful inhalation manoeuvre (out of 3 attempts) without assistance.2

Guidance

  • The BTS/SIGN guideline on the management of asthma suggests that when asthma control remains inadequate despite medium dose ICS/ long-acting β2 agonist (LABA), the following add-on treatment options could be trialled: leukotriene receptor antagonists, sustained release theophylline, or LAMA.5

Evidence for use

  • In two 48-week replicate, randomised, double-blind, placebo-controlled, parallel-group trials in adults with severe uncontrolled asthma:6
    • the mean (± standard error) difference between the tiotropium group and the placebo group in the change in the peak forced expiratory volume (FEV1) from baseline at week 24 (primary endpoint) was 86 ± 34 ml (trial 1; p=0.01) and 154 ± 32 ml (trial 2; p<0.001)
    • the time to first severe exacerbation (primary end point) was increased by 56 days with tiotropium compared with placebo (282 days vs 226 days): a relative risk reduction of 21% (hazard ratio, 0.79; 95% confidence interval (CI) 0.62 to 1.00; p=0.03)
    • adverse events (73.5% vs 80.3%) and serious adverse events (8.1% vs 8.8%) were similar between the tiotropium group and the placebo group, respectively
    • among the adverse events reported by at least 2% of patients, only allergic rhinitis occured at a significantly higher rate in the tiotropium group, whereas asthma events and insomnia were significantly more common in the placebo group
  • In a 12-week randomised, double-blind, placebo‑controlled, parallel-group trial in children (aged 6–11 years) with severe symptomatic asthma:7
    • adding tiotropium to ICS plus at least one controller significantly improved peak FEV1 response at week 12 compared with placebo (adjusted mean difference: 139 ml; 95% CI 75 ml to 203 ml; p<0.001)
    • the overall incidence of adverse events was similar between the Spiriva Respimat group and the placebo group (43.1% vs 43.4%)
  • In a 12-week randomised, double-blind, placebo-controlled, parallel-group trial in adolescents (aged 12–17 years) with severe symptomatic asthma:8
    • a change in peak FEV1 response at week 12 (primary endpoint) was observed with tiotropium but it was not statistically significant (90 ml; 95% CI –19 to 198; p=0.104)
    • the overall incidence of adverse events was similar between the Spiriva Respimat group and the placebo group (33.1% vs 35.6%)
    • the EMA approved Spiriva Respimat (5 μg dose only) for use in this patient population1 because the sizes of the FEV1 differences were consistent with those seen in severe asthma patients of other age ranges in which statistical significance was reached.6,9

Budgetary implications

  • Spiriva Respimat has a 30-day acquisition cost of £23.00 and is the only LAMA licensed in asthma3

References

  1. Boehringer Ingelheim Limited. Spiriva Respimat 2.5 microgram, inhalation solution—summary of product characteristics. March 2018. www.medicines.org.uk/emc/product/407/smpc (Accessed 7 November 2018)
  2. Kamin W, Krackhardt D, Gössl R et al. A handling study to assess the use of the Respimat® Soft Mist™ inhaler in children aged 4–12 years. Pulmonary Therapy 2015; 1: 53–63.
  3. Monthly Index of Medical Specialties. MIMS online. www.mims.co.uk (Accessed 7 November 2018)
  4. Zierenberg B. Optimizing the in vitro performance of Respimat. Journal of Aerosol Medicine 1999; 12: S19–S24.
  5. BTS/SIGN. British guideline on the management of asthma. SIGN 153. Edinburgh: SIGN, 2016. www.sign.ac.uk/sign-153-british-guideline-on-the-management-of-asthma.html
  6. Kerstjens HAM, Engel M, Dahl R et al. Tiotropium in asthma poorly controlled with standard combination therapy. The New England Journal of Medicine 2012; 367(13): 1198–1207.
  7. Szefler SJ, Murphy K, Harper T et al. A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma. The Journal of Allergy and Clinical Immunology 2017; 140: 1277–1287.
  8. Hamelmann E, Bernstein JA, Vandewalker M et al. A randomised controlled trial of tiotropium in adolescents with severe symptomatic asthma. European Respiratory Journal 2017; 49: 1601100
  9. European Medicines Agency. Reflection paper on the use of extrapolation in the development of medicines for paediatrics. EMA, 2017. https://www.ema.europa.eu/documents/scientific-guideline/draft-reflection-paper-use-extrapolation-development-medicines-paediatrics-revision-1_en.pdf

 

LAMA=long-acting muscarinic antagonist; ICS=inhaled corticosteroid; LABA=long-acting β2 agonist; FEV1 =forced expiratory volume; CI=confidence interval

 

PC-UK-100514 V1

Date of preparation: December 2018