SPIRIVA Inhalation powder, hard capsule Ref.[7493] Active ingredients: Tiotropium

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).

SPIRIVA capsules contain 5.5 mg lactose monohydrate. This amount does not normally cause problems in lactose intolerant patients. Patients with rare hereditary problems of galactose intolerance, the Lapp 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.

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 Spiriva during pregnancy.

Breast-feeding

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 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 should be made taking into account the benefit of breast-feeding to the child and the benefit of Spiriva therapy to the woman.

Fertility

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.

Summary of the safety profile

Many of the listed undesirable effects can be assigned to the anticholinergic properties of SPIRIVA.

Tabulated summary 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 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)

Description of selected adverse reactions

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.

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 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.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Not applicable.