Safety and undesirable effects in patients with asthma

The content below contains references to information available within the Summary of Product Characteristics and other published sources.

Many of the listed undesirable effects of tiotropium are a result of its anticholinergic properties. A common undesirable effect (≥1/100 to <1/10) is dry mouth.


Uncommon undesirable effects (≥1/1,000 to <1/100) include: dizziness, headache, insomnia, cough, pharyngitis, dysphonia, oropharyngeal candidiasis, bronchospasm and palpitations.1

Rare undesirable effects (> 1/10,000 to < 1/1,000) include: constipation, gingivitis, stomatitis, rash, pruritus, angioneurotic oedema, urticaria and hypersensitivity (including immediate reactions).1

Undesirable effects in patients with asthma where the frequency is unknown (because it cannot be estimated from available data) include:1

  • Dehydration
  • Glaucoma
  • An increase in intraocular pressure
  • Blurred vision
  • Atrial fibrillation
  • Supraventricular tachycardia
  • Tachycardia
  • Epistaxis
  • Laryngitis
  • Sinusitis
  • Dysphagia
  • Gastro-oesophageal reflux disease (GORD)
  • Dental caries
  • Glossitis
  • Intestinal obstruction (including paralytic ileus)
  • Nausea
  • Skin infection/skin ulcer
  • Dry skin
  • Anaphylactic reaction
  • Joint swelling
  • Urinary retention
  • Dysuria; and
  • Urinary tract infections

Description of selected adverse reactions

Serious undesirable effects that are consistent with the anticholinergic properties of tiotropium bromide include:1

  • Glaucoma
  • Constipation
  • Intestinal obstruction including paralytic ileus; and
  • Urinary retention

An increase in these anticholinergic effects may occur with increasing age.1


Overdose

High doses of tiotropium may lead to anticholinergic signs and symptoms. In healthy volunteers no systemic anticholinergic adverse effects have been seen following a single inhaled dose of up to 340 micrograms (mcg) of tiotropium bromide. No relevant adverse effects have been seen in healthy volunteers following 14-day dosing of up to 40 micrograms (mcg) of inhaled tiotropium solution except for a dry mouth or throat, dry nasal mucosa and a pronounced reduction in salivary flow (which has been observed from day 7 onwards).2


Interactions

No formal studies of drug interactions have been performed. Tiotropium bromide has been used concomitantly with other drugs that are commonly used in the treatment of patients with asthma and chronic obstructive pulmonary disease (COPD), including sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids, antihistamines, mucolytics, leukotriene modifiers, cromones and anti-IgE treatments without clinical evidence of drug interactions. The co-administration of tiotropium bromide with other anticholinergic-containing drugs has not been studied and is not recommended.3


Contraindications

The use of SPIRIVA®Respimat® is contraindicated in patients with hypersensitivity to tiotropium bromide, atropine or its derivatives (for example, ipratropium or oxitropium) or to any of the excipients4 which are listed below:5

  • Benzalkonium chloride
  • Disodium edetate

Special warnings and precautions for use

SPIRIVA® Respimat® should not be used for the relief of acute symptoms of asthma or for the initial treatment of patients with acute episodes of bronchospasm. It should not be used as (first-line) monotherapy for patients with asthma. Once a patient starts using SPIRIVA®Respimat®, clinicians should advise them to continue taking their current anti-inflammatory therapy (e.g. inhaled corticosteroids), unchanged, even if they experience an improvement in their symptoms.6

SPIRIVA®Respimat® is not recommended for the treatment of patients with cystic fibrosis (CF) because it may increase the signs and symptoms of CF (for example, serious adverse events, pulmonary exacerbations, respiratory tract infections).6


Special populations

Geriatric patients can use tiotropium bromide at the recommended dose. Patients with impairment of hepatic function can also use tiotropium bromide at the recommended dose.7


Patients with moderate to severe renal impairment

Patients with renal impairment can use tiotropium bromide at the recommended dose however, in patients with moderate to severe renal impairment (creatinine clearance ≤ 50ml/min), clinicians should weigh the expected benefits of using tiotropium bromide against the potential risks. In these patients, the impairment in renal function is associated with an increase in the plasma concentration of tiotropium bromide. There is no long-term experience of the use of tiotropium bromide in patients with severe renal impairment.6


Cautions

Patients may experience immediate hypersensitivity reactions and inhalation-induced bronchospasm after taking inhaled tiotropium bromide.6

Caution is also necessary when considering the use of tiotropium bromide in patients with:6

  • Narrow-angle glaucoma
  • Prostatic hyperplasia
  • Obstruction of the bladder neck
  • A history of myocardial infarction within the last six months
  • Cardiac arrhythmias that are unstable or life-threatening
  • Cardiac arrhythmias for which they have needed an intervention or a change in drug treatment within the past year
  • Admission to hospital for heart failure (New York Heart Association (NYHA) Class III or IV) within the past year.

Clinicians should advise patients who are using SPIRIVA® Respimat®to avoid getting the spray into their eyes because this could cause:6

  • Eye pain or discomfort
  • Temporary blurring of vision
  • Precipitation or worsening of narrow-angle glaucoma
  • Visual halos or coloured images
  • Conjunctival congestion and
  • Corneal oedema.

If a patient develops any of these eye symptoms they should stop using tiotropium bromide and consult a specialist immediately.

Dry mouth, which has been observed with anti-cholinergic treatment, may be associated with dental caries in the long-term.6


Pregnancy and breast-feeding

There is very limited amount of data about the use of tiotropium bromide in pregnant women and, as a precaution it is preferable to avoid prescribing SPIRIVA® Respimat® for pregnant women. It is not known whether tiotropium bromide is excreted in human breast milk and the use of SPIRIVA® Respimat® is not recommended in women who are breast-feeding.8