Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2022 Publisher: Boehringer Ingelheim International GmbH, Binger Strasse 173, 55216 Ingelheim am Rhein, Germany
Hypersensitivity to tiotropium bromide or to any of the excipients listed in section 6.1 or to atropine or its derivatives, e.g. ipratropium or oxitropium.
Excipients: Benzalkonium chloride may cause wheezing and breathing difficulties. Patients with asthma are at an increased risk for these adverse events.
Tiotropium bromide, as a once daily maintenance bronchodilator, should not be used for the initial treatment of acute episodes of bronchospasm, or for the relief of acute symptoms. In the event of an acute attack a rapid-acting beta-2-agonist should be used.
Spiriva Respimat should not be used as monotherapy for asthma. Asthma patients must be advised to continue taking anti-inflammatory therapy, i.e. inhaled corticosteroids, unchanged after the introduction of Spiriva Respimat, even when their symptoms improve.
Immediate hypersensitivity reactions may occur after administration of tiotropium bromide inhalation solution.
Consistent with its anticholinergic activity, tiotropium bromide should be used with caution in patients with narrow-angle glaucoma, prostatic hyperplasia or bladder-neck obstruction.
Inhaled medicines may cause inhalation-induced bronchospasm.
Tiotropium should be used with caution in patients with recent myocardial infarction <6 months; any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy in the past year; hospitalisation of heart failure (NYHA Class III or IV) within the past year. These patients were excluded from the clinical trials and these conditions may be affected by the anticholinergic mechanism of action.
As plasma concentration increases with decreased renal function in patients with moderate to severe renal impairment (creatinine clearance ≤50 ml/min) tiotropium bromide should be used only if the expected benefit outweighs the potential risk. There is no long term experience in patients with severe renal impairment (see 5.2).
Patients should be cautioned to avoid getting the spray into their eyes. They should be advised that this may result in precipitation or worsening of narrow-angle glaucoma, eye pain or discomfort, temporary blurring of vision, visual halos or coloured images in association with red eyes from conjunctival congestion and corneal oedema. Should any combination of these eye symptoms develop, patients should stop using tiotropium bromide and consult a specialist immediately.
Dry mouth, which has been observed with anti-cholinergic treatment, may in the long term be associated with dental caries.
Tiotropium bromide should not be used more frequently than once daily (see 4.9).
Spiriva Respimat is not recommended in cystic fibrosis (CF). If used in patients with CF, Spiriva Respimat may increase the signs and symptoms of CF (e.g. serious adverse events, pulmonary exacerbations, respiratory tract infections).
Although no formal drug interaction studies have been performed, tiotropium bromide has been used concomitantly with other drugs commonly used in the treatment of COPD and asthma, including sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids, antihistamines, mucolytics, leukotriene modifiers, cromones, anti-IgE treatment without clinical evidence of drug interactions.
Use of LABA or ICS was not found to alter the exposure to tiotropium.
The co-administration of tiotropium bromide with other anticholinergic containing drugs has not been studied and therefore is not recommended.
There is a very limited amount of data from the use of tiotropium in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity at clinically relevant doses (see 5.3). As a precautionary measure, it is preferable to avoid the use of Spiriva Respimat during pregnancy.
It is unknown whether tiotropium bromide is excreted in human breast milk. Despite studies in rodents which have demonstrated that excretion of tiotropium bromide in breast milk occurs only in small amounts, use of Spiriva Respimat is not recommended during breast-feeding. Tiotropium bromide 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.
Clinical data on fertility are not available for tiotropium. A non-clinical study performed with tiotropium showed no indication of any adverse effect on fertility (see 5.3).
No studies on the effects on the ability to drive and use machines have been performed. The occurrence of dizziness or blurred vision may influence the ability to drive and use machinery.
Many of the listed undesirable effects can be assigned to the anticholinergic properties of tiotropium bromide.
The frequencies assigned to the undesirable effects listed below are based on crude incidence rates of adverse drug reactions (i.e. events attributed to tiotropium) observed in the tiotropium group pooled from 7 placebo-controlled clinical trials in COPD (3,282 patients) and 12 placebo-controlled clinical trials in adult and paediatric patients with asthma (1,930 patients) with treatment periods ranging from four weeks to one year.
Frequency is defined using the following convention: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
| System Organ Class / MedDRA Preferred Term | Frequency COPD | Frequency Asthma |
|---|---|---|
| Metabolism and nutrition disorders | ||
| Dehydration | Not known | Not known |
| Nervous system disorders | ||
| Dizziness | Uncommon | Uncommon |
| Headache | Uncommon | Uncommon |
| Insomnia | Rare | Uncommon |
| Eye disorders | ||
| Glaucoma | Rare | Not known |
| Intraocular pressure increased | Rare | Not known |
| Vision blurred | Rare | Not known |
| Cardiac disorders | ||
| Atrial fibrillation | Rare | Not known |
| Palpitations | Rare | Uncommon |
| Supraventricular tachycardia | Rare | Not known |
| Tachycardia | Rare | Not known |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | Uncommon | Uncommon |
| Pharyngitis | Uncommon | Uncommon |
| Dysphonia | Uncommon | Uncommon |
| Epistaxis | Rare | Rare |
| Bronchospasm | Rare | Uncommon |
| Laryngitis | Rare | Not known |
| Sinusitis | Not known | Not known |
| Gastrointestinal disorders | ||
| Dry Mouth | Common | Uncommon |
| Constipation | Uncommon | Rare |
| Oropharyngeal candidiasis | Uncommon | Uncommon |
| Dysphagia | Rare | Not known |
| Gastrooesophageal reflux disease | Rare | Not known |
| Dental caries | Rare | Not known |
| Gingivitis | Rare | Rare |
| Glossitis | Rare | Not known |
| Stomatitis | Not known | Rare |
| Intestinal obstruction, including ileus paralytic | Not known | Not known |
| Nausea | Not known | Not known |
| Skin and subcutaneous tissue disorders, immune system disorders | ||
| Rash | Uncommon | Uncommon |
| Pruritus | Uncommon | Rare |
| Angioneurotic oedema | Rare | Rare |
| Urticaria | Rare | Rare |
| Skin infection/skin ulcer | Rare | Not known |
| Dry skin | Rare | Not known |
| Hypersensitivity (including immediate reactions) | Not known | Rare |
| Anaphylactic reaction | Not known | Not known |
| Musculoskeletal and connective tissue disorders | ||
| Joint swelling | Not known | Not known |
| Renal and urinary disorders | ||
| Urinary retention | Uncommon | Not known |
| Dysuria | Uncommon | Not known |
| Urinary tract infection | Rare | Rare |
In controlled clinical studies in COPD, the commonly observed undesirable effects were anticholinergic undesirable effects such as dry mouth which occurred in approximately 2.9% of patients. In asthma the incidence of dry mouth was 0.83%.
In 7 clinical trials in COPD, dry mouth led to discontinuation in 3 of 3,282 tiotropium treated patients (0.1%). No discontinuations due to dry mouth were reported in 12 clinical trials in asthma (1,930 patients).
Serious undesirable effects consistent with anticholinergic effects include glaucoma, constipation, intestinal obstruction including ileus paralytic and urinary retention.
The safety database includes 560 paediatric patients (296 patients aged 1 to 11 and 264 patients aged 12 to 17) from 5 placebo-controlled clinical trials with treatment periods ranging between 12 weeks to one year. The frequency, type and severity of adverse reactions in the paediatric population are similar as in adults.
An increase in anticholinergic effects may occur with increasing age.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme: Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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