Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Glenmark Pharmaceuticals Europe Limited, Laxmi House, 2B Draycott Avenue, Kenton, Middlesex, HA3 0BU, United Kingdom
Hypersensitivity to the active substance or to the excipient listed in section 6.1 or to atropine or its derivatives, e.g. ipratropium or oxitropium.
Tiotropium bromide, as a once daily maintenance bronchodilator, should not be used for the initial treatment of acute episodes of bronchospasm, i.e. rescue therapy.
Immediate hypersensitivity reactions may occur after administration of tiotropium bromide inhalation powder.
Consistent with its anticholinergic activity, tiotropium bromide should be used with caution in patients with narrow-angle glaucoma, prostatic hyperplasia or bladder-neck obstruction. (See section 4.8).
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 section 5.2).
Patients should be cautioned to avoid getting the drug powder 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 section 4.9).
Tiogiva capsules contain 5.2 mg lactose (corresponding to 5.5 mg lactose monohydrate). Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. The excipient lactose monohydrate may contain small amounts of milk proteins which may cause allergic reactions.
Although no formal drug interaction studies have been performed, tiotropium bromide inhalation powder has been used concomitantly with other drugs without clinical evidence of drug interactions. These include sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids, commonly used in the treatment of COPD.
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 is therefore 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 section 5.3). As a precautionary measure, it is preferable to avoid the use of Tiogiva 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 Tiotropium is not recommended during breast-feeding. Tiotropium bromide is a long-acting compound. A decision on must be made whether to continue/discontinue breast-feeding or to continue/discontinue/abstain from therapy with Tiogiva therapy should be made taking into account the benefit of breast-feeding to for the child and the benefit of Tiogiva therapy to for 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 section 5.3).
No studies on the effects on the ability to drive and use machines have been performed. The occurrence of dizziness, blurred vision, or headache may influence the ability to drive and use machinery.
Many of the listed undesirable effects can be assigned to the anticholinergic properties of Tiotropium.
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 (9,647 patients) from 28 pooled placebo-controlled clinical trials with treatment periods ranging from four weeks to four years.
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 |
|---|---|
| Metabolism and nutrition disorders Dehydration | Not known |
| Nervous system disorders Dizziness Headache Taste disorders Insomnia | Uncommon Uncommon Uncommon Rare |
| Eye disorders Vision blurred Glaucoma Intraocular pressure increased | Uncommon Rare Rare |
| Cardiac disorders Atrial fibrillation Supraventricular tachycardia Tachycardia Palpitations | Uncommon Rare Rare Rare |
| Respiratory, thoracic and mediastinal disorders Pharyngitis Dysphonia Cough Bronchospasm Epistaxis Laryngitis Sinusitis | Uncommon Uncommon Uncommon Rare Rare Rare Rare |
| Gastrointestinal disorders Dry mouth Gastro-oesophageal reflux disease Constipation Oropharyngeal candidiasis Intestinal obstruction, including ileus paralytic Gingivitis Glossitis Dysphagia Stomatitis Nausea Dental caries | Common Uncommon Uncommon Uncommon Rare Rare Rare Rare Rare Rare Not known |
| Skin and subcutaneous tissue disorders, immune system disorders Rash Urticaria Pruritus Hypersensitivity (including immediate reactions) Angioedema Anaphylactic reaction Skin infection, skin ulcer Dry skin | Uncommon Rare Rare Rare Rare Not known Not known Not known |
| Musculoskeletal and connective tissue disorders Joint swelling | Not known |
| Renal and urinary disorders Dysuria Urinary retention Urinary tract infection | Uncommon Uncommon Rare |
In controlled clinical studies, the commonly observed undesirable effects were anticholinergic undesirable effects such as dry mouth which occurred in approximately 4% of patients.
In 28 clinical trials, dry mouth led to discontinuation in 18 of 9,647 tiotropium treated patients (0.2%).
Serious undesirable effects consistent with anticholinergic effects include glaucoma, constipation and intestinal obstruction including ileus paralytic as well as urinary retention.
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 at www.mhra.gov.co.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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