Tiotor 16 micrograms Hard capsule for inhalation

TIOTOR 10 is indicated for the long-term maintenance treatment of chronic obstructive pulmonary disease (COPD), including chronic bronchitis and chronic bronchitis associated with emphysema.

Posology
Recommended dosage: Inhale the contents of one capsule once daily, at the same time each day, using the Zephir Inhaler device. TIOTOR 10 capsules must not be swallowed. Optimum efficacy can only be expected within a few days of usage.
Special Populations:
Elderly patients can use the recommended dose of TIOTOR 10 capsules for inhalation. Renally impaired patients can use tiotropium at the recommended dose. However, TIOTOR 10 use should be monitored closely in patients with moderate to severe renal impairment (see sections 4.4 and 5.2). Hepatically impaired patients can use TIOTOR 10 at the recommended dose (see section 5.2).
Paediatric population
The safety and efficacy in children have not been established. No data are available.
Method of administration
To ensure proper administration of the TIOTOR 10 the patient should be trained how to use the inhaler by the medical practitioner or by other healthcare professionals. The Zephir Inhaler is especially designed for TIOTOR 10. The Zephir Inhaler must not be used it to take any other medication. Zephir Inhaler can be used for up to one year to take TIOTOR 10.

Hypersensitivity to tiotropium bromide or to atropine or its derivatives, e.g. ipratropium or oxitropium or to any excipient of TIOTOR 10 listed in section 6.1. Contraindicated in children below 18 years as safety and efficacy have not been demonstrated.

Tiotropium bromide as contained in TIOTOR 10, 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 TIOTOR 10 inhalation powder. Consistent with its anticholinergic activity, TIOTOR 10 should be used with caution in patients with narrow-angle glaucoma, prostatic hyperplasia or bladder-neck obstruction. (see section 4.8). Inhaled TIOTOR 10 may cause inhalation-induced bronchospasm. TIOTOR 10 should be used with caution in patients with recent myocardial infarction < 6 months; any unstable or life-threatening cardiac dysrhythmia or cardiac dysrhythmia requiring intervention or a change in medicine 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 u2264 50 ml/min), the use of TIOTOR 10 should be monitored closely in these patients. There is no long-term experience in patients with severe renal impairment (see section 5.2). Patients should be cautioned to avoid getting the medicine 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 TIOTOR 10 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. TIOTOR 10 should not be used more frequently than once daily (see section 4.9). TIOTOR 10 contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take TIOTOR 10.

Although no formal medicine interaction studies have been performed, TIOTOR 10 inhalation powder has been used concomitantly with other medicines without clinical evidence of medicine interactions. These include sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids, commonly used in the treatment of COPD. Use of long-acting u03b22 agonists (LABA) or inhaled corticosteroids (ICS) was not found to alter the exposure to tiotropium. The co-administration of TIOTOR 10 with other anticholinergic-containing medicines has not been studied and is therefore not recommended.

Pregnancy
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 TIOTOR 10 during pregnancy.
Breastfeeding
It is unknown whether TIOTOR 10 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 TIOTOR 10 is not recommended during breast-feeding. Tiotropium bromide as contained in TIOTOR 10 is a long-acting compound. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with TIOTOR 10 should be made taking into account the benefit of breast-feeding to the child and the benefit of TIOTOR 10 therapy to the woman.
Fertility
Clinical data on fertility are not available for TIOTOR 10. An animal 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.

a. Summary of the safety profile
Many of the listed undesirable effects can be assigned to the anticholinergic properties of TIOTOR 10.
b. Tabulated list of adverse reactions
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 placebo controlled clinical trials with treatment periods ranging from four weeks to four years.
System Organ Class (MedDRA)
Frequency
Adverse reaction
Metabolism and nutrition disorders
Frequency unknown
Dehydration
Nervous system disorders
Less frequent
Dizziness, headache, taste disorders, insomnia
Eye disorders
Less frequent
Blurred vision, glaucoma, increased intraocular pressure
Cardiac disorders
Less frequent
Atrial fibrillation, supraventricular tachycardia, tachycardia, palpitations
Respiratory, thoracic and mediastinal disorders
Less frequent
Pharyngitis, dysphonia, cough, bronchospasm, epistaxis, laryngitis, sinusitis
Gastrointestinal disorders
Frequent
Dry mouth
Less frequent
Gastro-oesophageal reflux disease, constipation, oropharyngeal candidiasis, intestinal obstruction, including ileus paralytic, gingivitis, glossitis, dysphagia, stomatitis, nausea
Frequency unknown
Dental caries, mouth ulceration, pharyngolaryngeal pain, hoarseness, throat irritation
Skin and subcutaneous tissue disorders
Less frequent
Rash, urticaria, pruritus, hypersensitivity (including immediate reactions), angioedema
Frequency unknown
Anaphylactic reaction, skin infection, skin ulcer, dry skin, pruritis
Musculoskeletal and connective tissue disorders
Frequency unknown
Joint swelling
Renal and urinary disorders
Less frequent
Dysuria, urinary retention, urinary tract infection
Description of selected adverse reactions
The most commonly observed undesirable effects were anticholinergic undesirable side effects such as dry mouth. Serious undesirable effects consistent with anticholinergic effects include glaucoma, constipation and intestinal obstruction including ileus paralytic as well as urinary retention. Other special population An increase in anticholinergic effects may occur with increasing age.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

High doses of tiotropium bromide may lead to anticholinergic signs and symptoms. Acute intoxication by inadvertent oral ingestion of TIOTOR 10 capsules is unlikely due to low oral bioavailability. Treatment is symptomatic and supportive.