HCP area

DuoResp Spiromax® er designet for å være intuitiv å bruke1-2

Unødvendig å koordinere

aktivering og inhalering

Klar ved bare å vippe dekselet ned Kun ett trinn for å klargjøre dosen

Dekselet sitter fast i inhalatoren med ruglet overflate, for at den skal være lettere å skyve ned




  • ‘Klikk’-lyd
    Bare én dose kan holdes i reservoaret om gangen, så gjentatt åpning vil ikke frigi noen ekstra doser1

  • Laktosesmak
    Pasienter kan fastslå når de har inhalert dosen
  • Presist telleverk
    Pasienter vil vite når inhalatoren er nesten tom


  1. DuoResp Spiromax® monografi, 2014.


Vitenskapelige data til DuoResp Spiromax®

DuoResp Spiromax® er en tørrpulverinhalator som inneholder flere doser av  en fast dosekombinasjon (FDC) av budesonid, et inhalert kortikosteroid for å behandle den underliggende betennelsen i Astma og KOLS, og formoterolfumaratdihydrat, en hurtigvirkende og langvarig beta2-agonist for lindring av bronkokonstriksjon hos voksne pasienter med astma og KOLS.3

For mer detaljert informasjon om DuoResp Spiromax®, se nedenfor.

Effektivitet og sikkerhet

Effektiviteten og sikkerheten til DuoResp Spiromax® hos voksne og ungdom med astma: er basert på en randomisert sammenligning med Symbicort Turbuhaler®.

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Efficacy and safety of budesonide–formoterol (BF) Spiromax® in adults and adolescents with asthma: randomised comparison with BF Turbuhaler®

J. Christian Virchow, Gokul Gopalan, Roberto Rodriguez-Roisin, Youyi Shu

Thorax 2014, Volume 69, Suppl 2 - Poster Number 227 Presented at the BTS WINTER MEETING, London, UK, 03–05 December 2014


Correct inhaler technique is critical for effective asthma control.1

  • Several studies have highlighted that many patients don’t use their inhaler correctly, leading to poor asthma control 2−4
  • A device that is easy to use and with high patient acceptability, may improve inhaler technique and treatment adherence5.
  • Spiromax® is a multidose, dry-powder inhaler (DPI) that delivers fixed-dose combination therapy with an inhaled corticosteroid (ICS) (budesonide), and a long-acting β2 agonist (formoterol fumarate); DuoResp Spiromax®.
  • Pharmacokinetic studies have demonstrated therapeutic equivalence of medium and high strength BF Spiromax to BF Turbuhaler.7,8
  • This phase 3b study (A Spiromax® Safety and Efficacy Study compared to Turbuhaler® [ASSET]) was conducted to evaluate the efficacy and safety of DuoResp Spiromax® (160/4.5 μg [medium strength]) compared with Symbicort Turbuhaler® (200/6 μg [medium strength]) over 12 weeks in patients (≥12 years) with persistent asthma.




  • The primary objective was to establish the non-inferiority of DuoResp Spiromax® (160/4.5 μg) compared with Symbicort Turbuhaler® (200/6 μg).
  • The secondary objective was to evaluate patient preference and ease of use of DuoResp Spiromax® compared with Symbicort Turbuhaler® and to assess safety and tolerability of DuoResp Spiromax® (160/4.5 μg).
  • The primary endpoint was the change from baseline in the weekly average of daily trough morning (AM) peak expiratory flow (PEF), over the 12-week treatment period.
  • Secondary endpoints included:
    • the change from baseline in the weekly average of daily evening (PM) PEF over the 12-week treatment period
    • the change from baseline in the percentage of symptom-free 24-hour periods during the 12-week treatment period
    • the change from baseline in the percentage of rescue-free 24-hour periods during the 12-week treatment period
    • the change from baseline in the trough (AM pre-dose and pre-rescue bronchodilator) forced expiratory volume in 1 second (FEV1) over the 12-week treatment period.



Study design

  • This was a phase 3b, 12-week, multicentre (17 countries; 120 centres), randomised, double-blind, double-dummy, active-controlled, parallel-group study. The study included a screening and run-in period, followed by a 12-week, double-blind treatment period (Figure 1).

ASSET study design

FIGURE 1. ASSET study design. *Permitted asthma therapies: fluticasone propionate, beclomethasone dipropionate, budesonide, flunisolide, triamcinolone acetonide, mometasone furoate, ciclesonide

  • All patients received both a Spiromax® and a Turbuhaler® device (one placebo and one active therapy).
  • Patients were randomised 1:1 to receive either DuoResp Spiromax® or Symbicort Turbuhaler®:
    • two inhalations twice daily (BID) of DuoResp Spiromax® + two inhalations BID of placebo Turbuhaler® (Spiromax® group)
    • two inhalations BID Symbicort Turbuhaler®+ two inhalations BID of placebo Spiromax® (Turbuhaler® group).
  • Salbutamol was provided as rescue medication.


Key inclusion criteria:

  • ≥12 years old
  • asthma control questionnaire (ACQ) score ≥1.0
  • persistent asthma, with an FEV1 40−85%, and that has been stable for at least 30 days before the screening visit
  • ≥12% reversibility of FEV1 (and 200 mL increase), within 30 minutes following 2 inhalations of salbutamol
  • use of short-acting β2 agonists (SABA) and ICS for ≥8 weeks before screening, with maintenance on a stable dose of ICS for 4 weeks
  • able to replace current SABA with salbutamol for use, as needed, throughout the study.


Key exclusion criteria:

  • history of life-threatening asthma
  • bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear during the 2 weeks before the screening visit
  • asthma exacerbation requiring oral corticosteroids within one month of the screening visit
  • use of systemic, oral or depot corticosteroids within 4 weeks before the screening visit
  • use of tobacco products within 12 months before screening visit, or smoking history of ≥10 pack years




  • PEF was measured AM and PM by the patient, using a hand-held electronic peak flow meter.
  • FEV1 measurement was carried out electronically by spirometry at the clinic visits (between 07.00−11.00) and within ±1 hour of the time of the spirometry testing at the screening visit.
  • Asthma symptom scores were recorded by the patient on a linear scale from 0–5 (PM assessment; 0=no symptoms during the day and 5=symptoms so severe that the patient could not go to work or perform normal daily activities).
  • Safety was monitored throughout the study by recording of adverse events (AEs), oropharyngeal examination for candidiasis, clinical laboratory testing and measurement of vital signs.
  • Non-inferiority was established if the lower limit of the two-sided 95% confidence interval (CI) for the treatment difference in change from baseline in weekly average of daily trough AM PEF over the 12-week treatment period, was greater than −15 L/min.
  • Efficacy analyses included the per protocol (PP) population (all randomised patients, excluding patients with major protocol violations).
  • Safety analyses included all randomised patients who received at least 1 dose of the study medication.




  • 605 patients were randomised (safety population, n=602; PP population, n=574) (Figure 2).
  • Demographics are shown in Table 1.

FIGURE 2. Study profile.*AE, n=3; protocol violation, n=3; withdrawal by subject, n=3; non-compliance, n=1; other, n=3 ** Protocol violation, n=5; withdrawal by subject, n=3; AE, n=2; lost to follow-up, n=2; non-compliance, n=1; other n=5

Demographics of intent-to-treat population

TABLE 1. Demographics of intent-to-treat population.



Pulmonary function:

  • The least squares (LS) mean change from baseline in the weekly average of daily trough AM PEF over the 12-week treatment period was similar for both DuoResp Spiromax® and Symbicort Turbuhaler® (Table 2; Figure 3).
  • Non-inferiority was achieved:
    • the lower limit of the 95% two-sided CI (–9.02 L/min) is greater than –15 L/min.

The change from baseline in the weekly average of daily trough AM PEF

TABLE 2. The change from baseline in the weekly average of daily trough AM PEF (L/MIN).
LS = least squares

Mean change in average weekly morning PEF

FIGURE 3. Mean change in average weekly morning PEF.

Data shown are mean change from baseline based on weekly average values. Error bars represent standard deviation (SD). * Declined to n=263 by Week 12; **declined to n=256 by Week 12


  • The mean change from baseline in the weekly average of daily trough PM PEF over the 12-week treatment period was also similar for both treatment groups (DuoResp Spiromax® 18.661 L/min; Symbicort Turbuhaler® 21.740 L/min; 95% CI: –8.82, 2.67; p=0.2930).
  • The LS mean change from baseline in the trough (AM pre-dose and pre-rescue bronchodilator) FEV1 (L) over the 12-week treatment period was also similar for both DuoResp Spiromax® and Symbicort Turbuhaler® (0.325 and 0.318, respectively; 95% CI: –0.04, 0.06; p=0.7661; Figure 4).


Mean change in trough FEV1

FIGURE 4. Mean change in trough FEV1.


  • AEs were similar in the two study groups (Table 3).
    • 39% of patients in the DuoResp Spiromax® group and 35% in the Symbicort Turbuhaler® group experienced ≥1 AE.
    • Serious AEs (SAEs) were experienced by <1% of patients in the DuoResp Spiromax® group and by 1% in the Symbicort Turbuhaler® group.



TABLE 3. AEs (≥2%).


  • DuoResp Spiromax® 160/4.5 μg was shown to be non-inferior to Symbicort Turbuhaler® 200/6 μg, in relation to efficacy in the treatment of asthma.
  • There were no apparent differences between the two products in safety and tolerability.



  1. Crompton GK, et al. Respir Med. 2006;100:1479–1494.
  2. Smith IJ, et al. J Aerosol Med Pulm Drug Deliv 2010;23(suppl. 2):S25–37.
  3. Melani AS, et al. Med 2011;105:930–8.
  4. Al-Jahdali H, et al. Allergy Asthma Clin Immunol. 2013 Mar 6;9(1):8.
  5. Lavorini F, et al. Expert Opin Drug Deliv 2014;11:1–3.
  6. Arp J, et al. Presented at DDL 2013:abstr 66.
  7. Weisfeld L, et al. Eur Respir J 2013; 42(suppl. 57): P712.
  8. Weisfeld L, et al. Eur Respir J 2013; 42(suppl. 57): P4630.
  9. Gopalan G, et al. Allergy. 2014;69(99).

Håndtering av inhalatorer

Gransker håndteringsfeil av inhalator over tid i et helsepersonell perspektiv.

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Investigating handling errors over time for inhaler devices: the healthcare professional perspective*

Sinthia Bosnic-Anticevich, Daina Lim, Jo Steel, Vicky Kritikos, Vasilis Nikolaou, Leif Bjermer, Henry Chrystyn, Federico Lavorini, Richard PN Dekhuijzen, Cynthia Rand, Nicolas Roche, Lorraine Smith, Lisa Pont, Smita Shah, Nicholas Zwar, David B. Price.

Poster ID 1785 Presented at the EAACI June 6-10, 2015

* Results from visit 2 of the HCP Easy Low Instruction Over Time (ELIOT) study


  • Poor inhaler technique has been identified as an important reason for chronic suboptimal asthma control1.
  • The 2015 Global Initiative for Asthma (GINA) advises healthcare practitioners (HCPs) to train and assess patients in the use of inhalers at every clinical consultation2.
  • When HCPs show patients how to use their inhalers and what specific handling errors to avoid, correct inhaler technique is achieved by all patients and is maintained by the majority of patients3.
  • Use of a more intuitive dry powder inhaler device, for example Spiromax®, might be associated with fewer device handling errors made by HCPs compared with Turbohaler®4.



To investigate the nature and difference in handling errors made by undergraduate healthcare trainees in the use of two dry powdered inhalers, Turbohaler® and Spiromax®.

Percentage of participants who achieved device mastery* by randomizationorder and training levels 1 and 2

Table 1. Percentage of participants who achieved device mastery* by randomization order and training levels 1 and 2 (visit 1).
* Defined as the absence of expert assessor-observed device errors;
*** p< 0.001 (Pearsonschi-square test)



Study procedure

Figure 1: Study procedure (visits 1 and 2).
** Identified a priori through expert group consensus and defined as errors potentially impairing drug delivery to the lungs
Defined as the absence of expert assessor-observed device errors


The percentage of participants achieving device mastery* for Spiromax® compared with Turbohaler®


1. The percentage of device handling errors for Spiromax® compared with Turbohaler®.
2. The number of handling errors observed for all levels in the six-level training process.

* Defined as the absence of expert-assessor observed device handling errors;
Identified a priori through expert group consensus and defined as errors potentially impairing drug delivery to the lungs.


Baseline demographics and clinical Characteristics in visit 2

Table 2: Baseline demographics and clinical Characteristics in visit 2



Primary outcome: maintenance ofdevice mastery in visit 2

Table 3: Primary outcome: maintenance of device mastery in visit 2.
At Visit 2, 317 (64%) participants had maintained device mastery using Spiromax® compared with 202 (41%) participants using Turbohaler®


Table 4. Percentage of participants who achieved device mastery by randomization order in training levels 1 and 2 (visit 2).
***p< 0.001 (Pearsonschi-square test)


 Secondary outcome: Device handlingerrors for all training levels in visit 2

Figure 2: Secondary outcome: Device handling errors for all training levels in visit 2


Common Spiromax<sup>®</sup> and Turbohaler<sup>®</sup> handling errors in visit 2

Table 5: Common Spiromax® and Turbohaler® handling errors in visit 2


Participants preferred inhalerdevice following visit 2

Figure 3: Participants preferred inhaler device following visit 2


  • A greater percentage of patients achieved device mastery with less training using Spiromax® compared with Turbohaler® when they used the device for the first time and when they had already received training on another device
  • Participants using Spiromax® required less training levels in order to achieve mastery, compared with Turbohaler®
  • Preparation and inhalation errors were common errors for both devices
  • More participants preferred Spiromax® than Turbohaler®



  1. Price D et al. Euro Respir J 2014;44:P1757
  2. The Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2015 http://www.ginasthma.org/documents/4
  3. Ovchinikova L, et al. J Asthma2011;48:616-24
  4. Symbicort®Turbohaler® 200/6 μg, Inhalation powder (budesonide 200 μg and formoterol fumarate dihydrate 6 μg inhalation powder) Summary of Product Characteristics; 2009

Egenskaper til en ideell inhalator

Hvilke egenskaper skal testes når man tester en ny ideell inhalator.

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Features of an ideal inhaler in testing a new inhaler device

Tadeusz Plusa, Pawel Bijos

International review of Allegergology & clinical immunology in family medicine. Number 1, volume XXI, 2015.


It is well known that an inhaler with greater ease of use should require less effort to teach patients how to use it and improve their compliance and therapy results. DuoResp Spiromax® is a recently developed dry powder inhaler designed for maximum ease of use.



The aim of study was to obtain opinions on the new DuoResp Spiromax® devise among asthma/COPD patients and healthcare professionals (HCPs) and to compare this inhaler with a currently used Turbohaler® or Accuhaler®.


The study was performed in 80 patients with asthma or COPD in 9 European countries. In all patients qualitative face-to-face 261 interviews were performed.
The second part of the study was focused on healthcare professionals (HCPs) including general practitioners and nurses – 20 per country (21 in Germany).
The 181 interviews with HCPs were performed. The respondent’s evaluation of the DuoResp Spiromax® took place on the basis of having seen a demonstration video, having had an opportunity to try the empty device and in case of HCP’s additionally on having read the product profile of the Spiromax®.
The study was conducted by the Health division GfK SE, Germany, which is a global independent market research company and was sponsored by TEVA Pharmaceuticals Europe B.V.


Almost three-quarters of patients (74%) said that the new device comes closer to their perception of an ideal inhaler. 76% of patients handled the new device correctly without receiving any instruction.
The main reasons for considering the new device as better than the currently used device were: automatic priming mechanism and better dose counter.
More than three-quarters of HCPs (77%) said that the new device comes closer to their perception of an ideal inhaler.
HCPs consider that the ideal inhaler should be easy to handle; provide confirmation of successful inhalation; be convenient; have an ergonomic size and shape.


Most asthma/COPD patients and HCPs regard the new Spiromax® as preferable to their current device (Turbohaler®). Main reasons for considering Spiromax® as being unique are as follows; automatic priming mechanism in one step by simply opening the cover, higher efficacy, safety and compliance (easier to use, better loading mechanism with minimal risk of errors, better dose counter, more ergonomic shape).

Sammenligning inhalasjonsflyt gjennom to forskjellige inhalatorer

Inhalasjonskarakteristikker til astmapasienter, KOLS-pasienter og friske frivillige med Spiromax®- og Turbuhaler®-inhalatorer: en randomisert  “cross-over” studie.

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Inhalation characteristics of asthma patients, COPD patients and healthy volunteers with the Spiromax® and Turbuhaler® devices: a randomised, cross-over study

Wahida Azouz, Philip Chetcuti, Harold Hosker, Dinesh Saralaya and Henry Chrystyn

BMC Pulmonary Medicine (2015) 15:47


Spiromax® is a novel dry-powder inhaler containing formulations of budesonide plus formoterol (BF).
The device is intended to provide dose equivalence with enhanced user-friendliness compared to BF Turbuhaler® in asthma and chronic obstructive pulmonary disease (COPD). The present study was performed to compare inhalation parameters with empty versions of the two devices, and to investigate the effects of enhanced training designed to encourage faster inhalation.



This randomised, open-label, cross-over study included children with asthma (n = 23), adolescents with asthma (n = 27), adults with asthma (n = 50), adults with COPD (n = 50) and healthy adult volunteers (n = 50). Inhalation manoeuvres were recorded with each device after training with the patient information leaflet (PIL) and after enhanced training using an In-Check Dial device.


After PIL training, peak inspiratory flow (PIF), maximum change in pressure (ΔP) and the inhalation volume (IV) were significantly higher with Spiromax® than with the Turbuhaler® device (p values were at least <0.05 in all patient groups). After enhanced training, numerically or significantly higher values for PIF, ΔP, IV and acceleration remained with Spiromax® versus Turbuhaler®, except for ΔP in COPD patients. After PIL training, one adult asthma patient and one COPD patient inhaled <30 L/min through the Spiromax compared to one adult asthma patient and five COPD patients with the Turbuhaler. All patients achieved PIF values of at least 30 L/min after enhanced training.


The two inhalers have similar resistance so inhalation flows and pressure changes would be expected to be similar.
The higher flow-related values noted for Spiromax® versus Turbuhaler® after PIL training suggest that Spiromax® might have human factor advantages in real-world use.
After enhanced training, the flow-related differences between devices persisted; increased flow rates were achieved with both devices, and all patients achieved the minimal flow required for adequate drug delivery.
Enhanced training could be useful, especially in COPD patients.



Uavhengig identifisering av brukerfeil for en ny tørrpulverinhalator (DPI), Spiromax®, og en annen DPI, Turbuhaler®, ved hjelp av en Delphi-prosess som involverer eksperter innenfor behandling av luftveier (RDE-er).

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Independent identification of handling errors for a new dry powder inhaler (DPI), Spiromax, and another DPI, Turbuhaler, using a Delphi process involving respiratory device experts (RDEs)

Charlie Hewitt, Sebastian Heinzmann, Guilherme Safioti, Gokul Gopalan

Poster 1772 - Presented at the EUROPEAN ACADEMY OF ALLERGY AND CLINICAL IMMUNOLOGY (EAACI) CONGRESS, Barcelona, Spain, 6–10 June, 2015


  • Correct use of inhalation devices by asthma and chronic obstructive pulmonary disease (COPD) patients is critical for optimal drug delivery to the peripheral airways.
    • Technical characteristics of an inhalation device can determine how well it is handled, thus potentially impacting drug delivery.
  • Studies have shown that inhaler use is often suboptimal, with estimates of improper inhaler use ranging from 20–82% of patients.1–5
    • Poor inhaler technique in asthma patients is associated with poorer asthma control, increased use of oral steroids and antimicrobials, and increased hospitalisation.2–4
  • This study was designed to identify the errors that are critical to effective drug delivery using either the established dry powder inhaler (DPI) Symbicort (budesonide/formoterol delivered as 160/4.5 mcg or 80/4.5 mcg per actuation using the inhalation device, Turbuhaler® [also known as Turbohaler®; AstraZeneca AB, Södertälje, Sweden]), or the new DPI DuoResp (budesonide/formoterol delivered as 160/4.5 mcg or 320/9 mcg using the inhalation device, Spiromax® [Teva Pharmaceuticals Europe B.V., Haarlem, The Netherlands]).
    • Using an independent panel of practising clinicians with a speciality in device handling in asthma or COPD, a Delphi process 6–8 was conducted to compile lists of potential handling errors when using these DPIs and reach a consensus on the errors most likely to be critical for effective drug deliver



  • The aims of this study were to independently establish what is considered an error when handling placebo versions of the Spiromax® or Turbuhaler® DPIs for the treatment of asthma or COPD, and to assign a level of severity to each of these errors, using the Delphi process.



  • Independent respiratory device experts (RDEs) were identified using a combination of searches on the Scopus® publications database (Elsevier B.V., Amsterdam, The Netherlands) and desk research (Figure 1).
    • RDEs were anonymous to each other throughout the study.
  • The Delphi process was comprised of four rounds of electronic questionnaires (Figure 1).
    • Round 1: participating RDEs were provided placebo Spiromax® and Turbuhaler® devices (identical to those that would be dispensed in Europe, but without the active ingredients) along with the patient instruction leaflets. RDEs were instructed to list potential handling errors for each device.
    • Round 2: RDEs were provided with a consolidated list of errors and asked to assign a severity rating to each error according to its negative impact on device functionality and potential treatment outcomes (error [score 1–3, minimal impact]; potentially critical [4–7, mild-to-moderate impact]; critical [8–10, significant impact]). RDEs were also asked to provide the reasoning for each score.
    • Round 3: RDEs were provided an individualised report displaying their responses relative to the consolidated group, and were allowed to revise their ratings based on the group scores and reasoning. If consensus was not achieved for ≥90% of the errors for each device, a fourth round was to be conducted.
    • Round 4: for errors in which consensus severity ratings were not reached in Round 3, RDEs reviewed the median ratings from Round 3 and voted to accept or decline these ratings as the consensus.
  • Scores obtained for each error in Rounds 2 and 3 were analysed using descriptive statistics and median scores were calculated.
    • Errors were ranked according to median scores within each of the three severity categories.
    • Interquartile ranges (IQRs) were calculated to give a measure of dispersion and, therefore, consensus.
    • Consensus for each error was deemed to have been reached when the IQR was ≤2, or if ≥80% of the RDEs assigned the error to the same severity category.

Outline of study processes

RDEs, respiratory device expertse

Figure 1. Outline of study processes. RDEs, respiratory device expertse


Study conduct

  • Ten RDEs agreed to participate in the study (Table 1).
    • One advisor misunderstood the task and his/her contributions were not included in Round 2.
    • Another advisor did not complete the Round 3 survey before the Round 4 survey was issued, thus his/her input was not included in Round 3.
  • Consensus was not reached for ≥90% of the errors after Round 3, thus a fourth round was conducted.
  • Some changes were made to the wording and design of the questionnaire following Round 1 to emphasise the intended definition of handling error.


Participating RDEs

RDEs, respiratory device expertse. Table 1. Participating RDEs.

  • Identification of errors using the Delphi process
  • In Round 1, a total of 29 potential errors were identified for Spiromax® and 31 for Turbuhaler® (data not shown).
  • Median severity scores assigned to each error in Round 2 did not change substantially between Rounds 2 and 3.
  • Following Round 3, consensus was reached for 11 (38%) errors for Spiromax® and 21 (68%) errors for Turbuhaler®.
  • In Round 4, the severity scores from Round 3 were accepted as consensus for a further nine Spiromax® and eight Turbuhaler® errors, bringing consensus of the potential errors identified in Round 1 to 69% for Spiromax® and 94% for Turbuhaler®. Following completion of Round 4, teleconferences were held with six RDEs to finalise the classification of the errors. A total of 16 errors were identified as being anomalous and were discussed during the TCs.
  • Following the teleconferences, four of these errors retained their original classification and 12 were re-classified.
    • For Spiromax®, six errors were removed as they were not considered to be valid handling errors for the device, and two errors classified as ‘potentially critical’ were re-classified as ‘error’ (not holding the breath for long enough following inhalation, and device not held upright during loading/inhalation).
    • For Turbuhaler®, five errors were removed as they were not considered to be valid handling errors for the device, and two errors that had originally only been identified for Spiromax® were added (not holding the breath for long enough following inhalation, and unable to/forgetting to breathe out fully prior to inhalation).
  • The finalised lists consisted of 22 potential errors for Spiromax® and 27 for Turbuhaler®, with four errors classified as ‘critical’ for Spiromax® and nine for Turbuhaler® (Table 2).
    • Not inhaling through the mouthpiece, exhaling into the device, incorrect mouth positioning, and failure to read the dose indicator correctly (potentially leading to use of empty device) were ‘critical’ errors for both devices.

Final error categorisation and roud 2 and 3 severity scores

Table 2. Final error categorisation and roud 2 and 3 severity scores*.

The wording of some of the errors was modified slightly between Round 3 and the final categorisation.
*Scoring on scale of 0–10 with defined boundaries of what constitutes ‘critical’ (e.g. 8–10/10), ‘potentially critical’ (e.g. 4–7/10), and ‘error’ (e.g. 0–3/10).
†Added following the teleconference calls after Round 4 of the Delphi process. IQR, interquartile range



  • Using the Delphi process, RDEs independently identified and reached consensus on potential handling errors for Spiromax® and Turbuhaler®, ranking the errors by severity.
  • Spiromax® was associated with fewer errors overall and fewer errors that were classified as ‘critical’ or ‘potentially critical’ compared with Turbuhaler®, suggesting that there may be less potential for ‘critical’ handling errors with Spiromax®.



  1. Molimard M, et al. J Aerosol Med 2003;16:249–54.
  2. Molimard M, et al. J Asthma 2008;45:109–13.
  3. Melani AS, et al. Respir Med 2011;105:930–8.
  4. Al-Jahdali H, et al. Allergy Asthma Clin Immunol 2013;9:8.
  5. Arora P, et al. Respir Med 2014;108:992–8.
  6. Gordon TJ. Futures Research Methodology, Washington, DC: American Council for the United Nations University,1994.
  7. Rowe G and Wright G. Int J Forecasting 1999;15:353–75.
  8. Hsu C-C and Sandford BA. Pract Assess Res Eval 2007;12:1–8.


Farmakokinetikk og farmakodynamikk

Bioekvivalens av budesonid og formoterol (BF) Spiromax® og BF Turbohaler® (med og uten aktivt kull) hos friske frivillige.

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Bioequivalence of budesonide plus formoterol (BF) Spiromax® and BF Turbohaler® (with and without charcoal block) in healthy volunteers.

Lori Weisfeld, Youyi Shu and Tushar P. Shah

International Journal of Clinical Pharmacology and Therapeutics, DOI 10.5414/CP202238.


Budesonide formoterol (BF) DuoResp Spiromax® is a breath-actuated dry-powder inhaler designed to deliver similar combinations of budesonide and formoterol as Symbicort Turbohaler®. We performed two studies to demonstrate pharmacokinetic (PK) equivalence of DuoResp Spiromax® with Symbicort Turbohaler®.



Two single-center, open-label, randomized, 5-period crossover studies were performed. The first study compared DuoResp Spiromax® 160/4.5 μg with Symbicort Turbohaler® 200/6 μg, while the second study compared DuoResp Spiromax® 320/9 μg with Symbicort Turbohaler® 400/12 μg. All treatments were administered with and without charcoal. PK parameters were calculated by measuring plasma drug concentrations from blood samples taken pre-dose and up to 24 hours post-dose.


In each study, 90 healthy volunteers were randomized. Bioequivalence of DuoResp Spiromax® with Symbicort Turbohaler® was demonstrated for budesonide and formoterol (AUC0–t and Cmax (90% confidence intervals of the geometric mean between-device ratios for both parameters were within the predefined range of 0.80 – 1.25 in both studies)).
Equivalence was observed without use of charcoal (overall absorption post-inhalation) and with charcoal (pulmonary absorption). There were no major differences between treatments in tmax for either budesonide or formoterol. All study treatments were well tolerated (one treatment-emergent adverse event (TEAE) in the medium-dose study and four TEAEs in the high-dose study).


These studies indicate that DuoResp Spiromax® (± charcoal block) is bioequivalent to Symbicort Turbohaler® with respect to the PK parameters assessed.
Single doses of DuoResp Spiromax® were well tolerated; the overall safety profile of DuoResp Spiromax® and Symbicort Turbohaler® was similar.

Parametre for lungedeponering

Effekten av Inhalasjonskarakteristikken og halsgeometrier av forventet lungedeponering av budesonid og formoterol (BF) når det er inhalert gjennom to forskjellige enheter.

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Effect of inhalation profiles and throat geometries on predicted lung deposition of budesonide and formoterol (BF) when inhaled through two different devices.

Henry Chrystyn, Guilherme Safioti, Johan René Keegstra, Gokul Gopalan.



An in vitro investigation to predict the effect of different mouth-throat geometries and COPD-related inhalation profiles on lung deposition of BF Spiromax® and BF Turbuhaler®.



  • In vitro methodology has been validated for predicting lung deposition of medication with different anatomical models of respiratory tract geometry (‘small’, ‘medium’ and ‘large’ adult).7
  • The following parameters were measured in order to predict lung deposition of BF: predicted lung dose (ex-throat), delivered dose (DD) fine particle dose (FPD), and particle size distribution (mass median aerodynamic diameter [MMAD] and the geometric standard diameter [GSD]).
  • BF Spiromax®(delivered dose, 320/9μg; metered dose 400/12μg) was compared with BF Turbuhaler® (delivered dose, 320/9μg; metered dose 400/12μg);2–4 replicates/experiment. Three different anatomical throat models were used plus an inlet specified by the United States Pharmacopeia (USP) and inhalation profiles to mimic COPD patients. The 10th (‘weak’), 50th (‘medium’) and 90th (‘strong’) percentile inhalations were selected based on peak flow and initial acceleration from a previous study.8
  • MMAD and FPD were measured by a Next Generation Pharmaceutical Impactor (NGI) with a connected mixing inlet to enable the replay of an inhalation profile through each DPI.7 DD was measured by placing a filter between the throat and the inhaler. One inhaler actuation was used per filter assessment and five actuations for each impactor test.



  • The overall mean ex-throat lung dose of BF was similar with Spiromax® (111.1/3.0μg) and Turbuhaler® (102.2/3.0μg). Average ex-throat budesonide lung dose for all inhalation profiles were 105.4−119.9μg with Spiromax® and 54.5−149.1μg with Turbuhaler® (Figure 1), and comparable to formoterol results.

Lung dose and average throat dose (in μg budesonide) for BF Turbuhaler<sup>®</sup> versus BF Spiromax<sup>®</sup>

Figure 1. Lung dose and average throat dose (in μg budesonide) for BF Turbuhaler® versus BF Spiromax®.

  • Overall ranges for MMAD were similar: Turbuhaler®, 1.6–3.7μm (budesonide) and 1.6–3.1μm (formoterol); Spiromax®: 1.5–2.7μm and 1.5–2.8μm respectively. MMAD was lower with Spiromax® for the weak inhalation profile (2.7 vs 3.2μm;).
  • For all throat geometries and inhalation profiles, GSD results were comparable for both devices. Formoterol MMAD and GSD results showed similar patterns to those observed for budesonide (data not shown).
  • Both the filter (Figure 1) and the NGI data indicate higher delivered doses with BF Spiromax® versus BF Turbuhaler®.
  • FPD data and ex-throat lung dose had similar overall trends. FPD was comparable with the two inhalers with the strong inhalation profile (60 l/min). FPD was higher with Spiromax® with weak/medium inhalation profiles (Figure 2).
  • NGI results for formoterol and budesonide were comparable for both delivered dose and fine particle fraction (data not shown).

Fine particle dose (FPD) of budesonide with BF Spiromax<sup>®</sup> and BF Turbuhaler<sup>®</sup>

Figure 2. Fine particle dose (FPD) of budesonide with BF Spiromax® and BF Turbuhaler® – results from Next.
Generation Pharmaceutical Impactor (NGI) analyses.


  • Overall, Turbuhaler® and Spiromax® delivered similar mean ex-throat lung doses of budesonide and formoterol. Turbuhaler® was more sensitive to variations in inhalation profile: Spiromax® was more sensitive to throat geometry.
  • Spiromax® delivered more consistent doses of budesonide and formoterol across a range of inspiratory flow profiles.
  • The FPD of the aerosol predicted to reach the lungs was similar for the two inhalers except with the weak inhalation profile, for which MMAD was lower with Spiromax®.



  1. Labiris NR, et al. Br J Clin Pharmacol 2003;56:588–99.
  2. Dolovich MB, Dhand R. Lancet 2011;377:1032–45.
  3. Zhou Y, et al. J Aerosol Med Pulm Drug Deliv 2011;24:277–84.
  4. Weisfeld L, et al. Eur Respir J 2013;42(suppl. 57):abstr 712.
  5. Weisfeld L, et al. Eur Respir J 2013;42(suppl. 57):abstr 4630.
  6. Arp J, et al. Presented at DDL 2013:abstr 66.
  7. Olsson B, et al. J Aerosol Med Pulm Drug Deliv 2013;26:355–69.
  8. Azouz WA, et al. Eur Respir J 2013;42(suppl. 57):abstr 711.



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Intuitivt design 1-2



  1. Rychlik R, Kreimendahl F. Presented at the 7th IPCRG World Conference, 2014.
  2. Płusa T, Bijoś P. Int Rev Allergol Clin Immunol Family Med, 2015; 21(1): 21–24.
  3. Sammendrag av produktegenskapene til DuoResp Spiromax®.