Special Warning : אזהרת שימוש

4.4     Special warnings and precautions for use
Asthma
Spiolto Respimat should not be used in asthma. The efficacy and safety of Spiolto Respimat in asthma have not been studied.


Not for acute use
Spiolto Respimat is not indicated for the treatment of acute episodes of bronchospasm, i.e. as rescue therapy.


Spiolto Respimat                                       Approved prescribing information Inhalation solution                                    May 2019
Paradoxical bronchospasm
As with other inhaled medicines Spiolto Respimat may result in paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs Spiolto Respimat should be discontinued immediately and alternative therapy substituted.

Anticholinergic effects related to tiotropium

Narrow-angle glaucoma, prostatic hyperplasia or bladder-neck obstruction Consistent with the anticholinergic activity of tiotropium, Spiolto Respimat should be used with caution in patients with narrow-angle glaucoma, prostatic hyperplasia or bladder-neck obstruction.


Eye symptoms
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 Spiolto Respimat and consult a specialist immediately.


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


Patients with renal impairment
As plasma concentration of tiotropium increases with decreased renal function in patients with moderate to severe renal impairment (creatinine clearance  50 ml/min) Spiolto Respimat 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).


Cardiovascular effects
The experience with Spiolto Respimat is limited in patients with a history of myocardial infarction during the previous year, unstable or life-threatening cardiac arrhythmia, hospitalized for heart failure during the previous year or with a diagnosis of paroxysmal tachycardia (>100 beats per minute) because these patients were excluded from the clinical trials. Spiolto Respimat should be used with caution in these patient groups.

Like other beta2-adrenergic agonists, olodaterol may produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, blood pressure, and/or symptoms. In case such effects occur, treatment may need to be discontinued. In addition, beta-adrenergic agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the T wave and ST segment depression, although the clinical significance of these observations is unknown.

Long acting beta2-adrenergic agonists should be administered with caution in patients with cardiovascular disorders, especially ischaemic heart disease, severe cardiac decompensation, cardiac arrhythmias, hypertrophic obstructive cardiomyopathy, hypertension, and aneurysm, in patients with convulsive disorders or thyrotoxicosis, in patients with known or suspected prolongation of the QT interval (e.g. QT> 0.44 s), and in patients who are unusually responsive to sympathomimetic amines.


Hypokalaemia
Beta2-adrenergic agonists may produce significant hypokalaemia in some patients, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually 
Spiolto Respimat                                      Approved prescribing information Inhalation solution                                   May 2019 transient, not requiring supplementation. In patients with severe COPD, hypokalaemia may be potentiated by hypoxia and concomitant treatment (see section 4.5), which may increase the susceptibility to cardiac arrhythmias.


Hyperglycaemia
Inhalation of high doses of beta2-adrenergic agonists may produce increases in plasma glucose.
Anaesthesia
Caution needs to be taken in case of a planned operation with halogenated hydrocarbon anaesthetics due to an increased susceptibility to the adverse cardiac effects of beta agonist bronchodilators.

Spiolto Respimat should not be used in conjunction with any other medications containing long-acting beta2-adrenergic agonists.
Patients who have been taking inhaled, short-acting beta2-adrenergic agonists on a regular basis (e.g.
four times a day) should be instructed to use them only for symptomatic relief of acute respiratory symptoms.

Spiolto Respimat should not be used more frequently than once daily.

Hypersensitivity
As with all medications, immediate hypersensitivity reactions may occur after administration of Spiolto Respimat.

Excipients
Benzalkonium chloride may cause wheezing and breathing difficulties. Patients with asthma are at an increased risk for these adverse events.

Effects on Driving

4.7   Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed.

Spiolto Respimat                                       Approved prescribing information Inhalation solution                                    May 2019
However, patients should be advised that dizziness and blurred vision have been reported with the use of Spiolto Respimat. Therefore, caution should be recommended when driving a car or operating machinery. If patients experience such symptoms, they should avoid potentially hazardous tasks such as driving or operating machinery.