Olodaterol

Monoamine oxidase inhibitors or tricyclic antidepressants or other drugs known to prolong the QTc interval may potentiate the action of olodaterol on the cardiovascular system.

Concomitant administration of other adrenergic agents (alone or as part of combination therapy) may potentiate the undesirable effects of olodaterol.

Beta-adrenergic blockers may weaken or antagonise the effect of olodaterol. Therefore olodaterol should only be given together with beta-adrenergic blockers (including eye-drops) if there are compelling reasons for their use. In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.

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.

Concomitant treatment with xanthine derivatives, steroids, or non-potassium sparing diuretics may potentiate any hypokalemic effect of adrenergic agonists.

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>0.44s), and in patients who are unusually responsive to sympathomimetic amines.

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) were excluded from the clinical trials. Therefore the experience in these patient groups is limited. Olodaterol should be used with caution in these patient groups.

There are no data from the use of olodaterol in pregnant women available.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity at clinically relevant exposures.

As a precautionary measure, it is preferable to avoid the use of olodaterol during pregnancy.

Like other beta₂-adrenergic agonists, olodaterol may inhibit labour due to a relaxant effect on uterine smooth muscle.

Clinical data from nursing women exposed to olodaterol are not available.

It is unknown whether olodaterol/metabolites are excreted in human milk. Available pharmacokinetic/toxicological data in animals have shown excretion of olodaterol and/or its metabolites in milk.

Since the systemic exposure of the breast-feeding woman to olodaterol/metabolites is negligible at the human dose of 5 µg per day, relevant effects on the breastfed newborn/infant are not expected.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from olodaterol therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

Clinical data on fertility are not available for olodaterol. Preclinical studies performed with olodaterol showed no adverse effect on fertility.

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

However, patients should be advised that dizziness has been reported in clinical trials. Therefore, caution should be recommended when driving a car or operating machinery. If patients experience dizziness, they should avoid potentially hazardous tasks such as driving or operating machinery.

a. Summary of the safety profile

The most common adverse reactions at the recommended dose were nasopharyngitis, dizziness, hypertension, rash and arthralgia. These were usually mild or moderate in intensity.

b. Tabulated summary of adverse reactions

The frequencies assigned to the undesirable effects listed below are based on the crude incidence rates of adverse drug reactions (i.e. events attributed to olodaterol) observed in the olodaterol 5 microgram dose group (1035 patients), pooled from 6 placebo-controlled, parallel group clinical trials in COPD patients with treatment periods ranging between 4 and 48 weeks.

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)

c. Description of selected adverse reactions

Occurrence of rash may be considered a hypersensitivity reaction with olodaterol; as with all topical absorbed medication, other hypersensitivity reactions may develop.

d. Beta₂-agonist adverse reaction profile

Olodaterol is a member of the therapeutic class of long-acting beta₂-adrenergic agonists. Therefore, the occurrence of undesirable effects related to the beta-adrenergic agonist class should be taken into consideration, such as tachycardia, arrhythmia, palpitations, myocardial ischaemia, angina pectoris, hypertension or hypotension, tremor, headache, nervousness, insomnia, dizziness, dry mouth, nausea, muscle spasms, fatigue, malaise, hypokalemia, hyperglycemia, and metabolic acidosis.