Frequently asked questions
Frequently Asked Questions cover a diverse range of subjects, including evidence from the SPIRIVA ® Respimat ® clinical trial programme, prescribing guidelines for SPIRIVA ® and the administration of SPIRIVA ® via the Respimat ® inhaler.
SPIRIVA® Respimat® – evidence from asthma clinical trials
The UniTinA-asthma® clinical trial programme set out to address the unmet need of patients who remain symptomatic despite maintenance therapies. It was designed to establish the efficacy and safety of SPIRIVA® (tiotropium) delivered by the Respimat® SoftMist™ Inhaler in patients with asthma. The programme included 18 trials in more than 150 sites globally. More than 6,000 asthma patients with a range of disease severities were involved.
The UniTinA-asthma® clinical trial programme, included data from the PrimoTinA-asthma® (NCT00772538/NCT00776984), MezzoTinA-asthma® (NCT01172808/NCT01172821) and GraziaTinA-asthma® (NCT01316380) studies. These evaluated SPIRIVA®(tiotropium) delivered via the Respimat® inhaler as add-on treatment for adults with asthma who continued to experience symptoms despite maintenance treatment with at least ICS. All parallel-group Phase II and III adult studies were of randomised, double-blind, placebo-controlled design of at least 12 weeks’ duration, in patients (aged 18–75 years) with symptomatic asthma. SPIRIVA® (tiotropium) or placebo were each administered as add-on therapy to ICS maintenance treatment with or without other background therapies.
SPIRIVA® Respimat® is a once-daily treatment with 24-hour duration of action. The data indicate that efficacy is independent of dosing time as a sustained treatment effect is evident for both morning and evening dosing schedules with continued efficacy over 24 hours.1-3 SPIRIVA® Respimat®should be administered once a day, around the same time every day.4
SPIRIVA® Respimat® is a once-daily treatment with 24-hours duration of action. The data indicate that efficacy is independent of dosing time as a sustained treatment effect is evident for both morning and evening dosing schedules with continued efficacy over 24 hours. Different administration times were chosen to match with background medication dosing (i.e. twice daily or evening dosing for ICS).1-3 SPIRIVA® Respimat®should be administered once a day around the same time every day.4
The results from the SPIRIVA® Respimat® in asthma programme demonstrated that SPIRIVA® Respimat® significantly improved lung function across all asthma severities studied, those lung function improvements also translated into a reduced risk of exacerbations/asthma worsenings and severe exacerbations and an increased likelihood of improved asthma control.1,2
The control groups took SPIRIVA® Respimat® placebo added to at least ICS (base line medication) so it is possibly due to increased compliance with their baseline medications in addition to the placebo effect from the non-active inhaler.
Results from seven Phase II and III randomised, double-blind, parallel-group trials of 12-52 weeks’ duration showed that the most common adverse events were asthma, nasopharyngitis, and decreased peak expiratory flow rate (PEF); asthma and decreased PEF were numerically higher in the placebo arms.5
‘Symptomatic asthma’ or ‘poorly controlled asthma’ refers to patients with an Asthma Control Questionnaire (ACQ) total score ≥1.5 at screening and before randomisation.1,2
In the PrimoTinA-asthma® trials, SPIRIVA® Respimat® demonstrated a positive response independent of allergic status. Pre-specified subgroup analyses were conducted for all major endpoints, the effect in the different subgroups was consistent with the overall response to SPIRIVA® Respimat®, demonstrating a beneficial response to SPIRIVA® Respimat® from all subgroups reviewed. The analyses of endpoints in patients based on allergic criteria, including, IgE, blood eosinophilia or TH2 status demonstrated a consistent positive response to SPIRIVA® Respimat®, which indicates response to SPIRIVA® Respimat® is independent of allergic status.1,6
SPIRIVA® Respimat® as add-on to ICS+LABA has been shown to be efficacious in all subgroups tested independent of baseline characteristics.1,6
The inclusion/exclusion criteria used for the PrimoTinA-asthma® trials were the generally established criteria for phase III trials in asthma. Only patients with acute and unstable cardiovascular diseases were excluded: patients with a recent history (i.e. six months or less) of myocardial infarction; patients who have been hospitalised for cardiac failure during the past year; patients with any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year.1
In the PrimoTinA-asthma® studies the time to the first exacerbation (the primary end point) was increased by 56 days with SPIRIVA® Respimat® as compared with placebo (282 days vs. 226 days, representing the time until at least 25% of the patients [first quartile] had a first severe exacerbation), corresponding to a statistically significant reduction of 21% in risk.1 This was supported by a significant reduction of 31% in risk for asthma worsening.4
In the PrimoTinA-asthma® trials, asthma control was assessed using the Asthma Control Questionnaire (ACQ). Based on the ACQ scores, a responder was defined as an improvement of 0.5 in the ACQ total score (the established minimally important difference (MID) is a change in the score of 0.5). The benefit with SPIRIVA® Respimat® was also assessed by the number of responders and the likelihood to be a responder treated with SPIRIVA® Respimat® compared to placebo (odds ratio). A post hoc analysis from the pooled PrimoTinA-asthma® trials, resulted in a 1.68 odds ratio of response at 48 weeks, meaning a 68% higher likelihood of improvement in asthma control compared to placebo.6
Pooled data from seven Phase II and III trials from the UniTinA-asthma® programme demonstrated that the frequencies of patients reporting AEs, SAEs and treatment-related AEs were comparable between SPIRIVA® Respimat®and placebo treatment groups. No deaths occurred during any of the trials.5
SPIRIVA® Respimat® and special populations
Renally impaired patients can use SPIRIVA® Respimat® at the recommended dose. In patients with moderate to severe renal impairment (creatinine clearance ≤ 50 ml/min) SPIRIVA® Respimat®should be used only if the expected benefit outweighs the potential risk. There is no long term experience in patients with severe renal impairment.4 SPIRIVA® Respimat® is approved for use in adults with asthma in the EU, Japan, the USA and many other countries. The label varies by country. Please refer to the local product information.
Hepatically impaired patients can use SPIRIVA®Respimat® at the recommended dose.4 SPIRIVA®Respimat® is approved for use in adults with asthma in the EU, Japan, the USA and many other countries. The label varies by country. Please refer to the local product information.
There is a very limited amount of data from the use of SPIRIVA® Respimat® in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity at clinically relevant doses. As a precautionary measure, it is preferable to avoid the use of SPIRIVA® Respimat® during pregnancy.4
It is unknown whether tiotropium is excreted in human breast milk. Despite studies in rodents that have demonstrated that excretion of tiotropium in breast milk occurs only in small amounts, use of SPIRIVA® Respimat® is not recommended during breast-feeding. Tiotropium is a long-acting compound. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with SPIRIVA® Respimat® should be made taking into account the benefit of breast-feeding to the child and the benefit of SPIRIVA® Respimat® therapy to the woman.4
SPIRIVA® Respimat® is approved for use in adults with asthma in the EU, Japan, the USA and many other countries. The label varies by country. Please refer to the local product information.
The efficacy and safety of SPIRIVA® Respimat® in children and adolescents has not yet been established.4 SPIRIVA® Respimat®is approved for use in adults with asthma in the EU, Japan, the USA and many other countries. The label varies by country. Please refer to the local product information.
Administration via Respimat® Soft Mist Inhaler (SMI) inhaler
Respimat® works mechanically, without a propellant. Before the first use, the solution with the medication needs to be drawn up through a tube. This will ensure patients get the full dose. Priming does not affect the number of doses available in the inhaler.
The dose indicator shows how many puffs of medicine are left. When the pointer enters the red area of the scale, there is approximately enough medication left for 7 days. This is when patients need to refill the prescription or ask you about whether they need another prescription for SPIRIVA® Respimat®. Once the dose indicator has reached the end of the scale, all puffs have been used and Respimat® locks automatically. At this point, the clear base of the inhaler cannot be turned.
In general the dose of medication delivered by Respimat® is precise and consistent. Since dosing is more precise when administered as two actuations versus one actuation for a product used once daily, it was Boehringer Ingelheim’s decision to use two actuations per dose for SPIRIVA® Respimat®. This is in agreement with all worldwide approvals and was accepted by all Health Authorities. (Administering the recommended medicinal dose as two actuations is not unusual for other inhalative products including pressurized metered dose inhalers (pMDIs)).
In order to receive a consistent and appropriate dose of SPIRIVA® Respimat®, treatment must be administered as two actuations once-daily. SPIRIVA® Respimat® is designed to accurately deliver the full dose of medication when two actuations are administered once daily in order to minimize dose-to-dose variability.
The success of inhaled respiratory therapies depends on the efficient delivery of the medication to the lungs via the inhaler. Only medication particles that reach the lungs and stay there can provide therapeutic effects. The therapeutic effect of an inhaled therapy depends on the dose deposited as well as its distribution in the lungs.
Patients need to breathe out slowly and fully, then close their lips around the mouthpiece. While taking in a slow deep breath, they need to press the dose release button and keep breathing in slowly.
SPIRIVA® Respimat® should be discarded three months after patients have prepared it for first use, even if it has not been fully used or used at all.4
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.4