Olodaterol

Olodaterol (brand name: Striverdi®) is a bronchodilator belonging to the group of beta-2-symptomimetics. It is used for the symptomatic long-term treatment of COPD, a chronic obstructive pulmonary disease in which the airways are permanently narrowed. It thus helps sufferers to breathe more easily.

It can be used alone or (since 2016) in combination with tiotropium, an anticholinergic.

Use & Indications

Olodaterol is inhaled both alone as a solution and in combination with other active ingredients, always using the Respiramat inhalation device.

This works purely mechanically and does not require any electrical energy, for example from a battery. During use, it generates a spray cloud consisting of very fine droplets that spreads very slowly. In contrast to conventional inhalation devices, this enables a more coordinated intake. Thus, less active ingredient remains in the mouth/throat and most of it reaches the lungs directly for a more targeted intake.

One dose comprises two sprays (2.5 µg/stroke), i.e. it must be sprayed and inhaled twice in succession. This application takes place once a day, always at the same time of day, since the duration of action of olodaterol is 24 hours.

This information applies to both Striverdi® and Spiolto®.

Pharmacodynamics/mechanism of action

Olodaterol acts as a bronchodilator by binding with very high selectivity as well as strong affinity to the beta-2-adrenoceptor - primarily in the lungs - and consequently activating it. After binding to the receptor, it dissociates (dissolves) only slowly, which explains the long-lasting effect of the drug.

Activation of the receptor stimulates adenylate cyclases. This increases the formation of cyclic adenosine monophosphate (cAMP), which then also activates cAMP-dependent protein kinase A (PKA). This leads to the reduction of intracellular ^Ca2+ through phosphorylation, preventing airway smooth muscle contraction.

Consequently, the increased formation of these two molecules causes bronchodilation by relaxing airway smooth muscle, making it easier for the COPD patient to breathe.

By mimicking endogenous catecholamines (epinephrine, norepinephrine), olodaterol thus exerts bronchodilator as well as partial anti-inflammatory effects as an adrenergic beta-2 agonist.

Pharmacokinetics

After inhalation, the maximum plasma concentration of the active substance is reached after 10-20 minutes. Bioavailability is high at 30%, being less than 1% when taken perorally (by mouth). However, it is also dependent on individual lung absorption and how much of the active ingredient is actually inhaled, as any portion swallowed or remaining in the mouth remains insignificant to the effect.

If olodaterol enters the metabolic system, then most of it is excreted in the feces (53%), with a smaller portion (38%) excreted renally.

Drug Interactions

• Olodaterol in combination with drugs that prolong the QTC interval, such as monoamino oxidase inhibitors, tricyclic antidepressants, corticosteroids, MAO inhibitors, etc., may be enhanced in its effect on the cardiovascular system and lead to cardiovascular problems.
• When interacted with other adrenergic agents that share the same mechanism, the effect may be mutually potentiated - whereas β-adrenoceptor blockers and olodaterol attenuate each other due to their opposite mechanism of action.
• Hypokalemia may occur with concomitant therapy of olodaterol with xanthine derivatives, steroids, or nonpotassium-sparing diuretics.

Contraindications & Precautions

Olodaterol must not be used in case of:

• hypersensitivity to the active substance
• asthma
• acute bronchospasm

Caution should be exercised in patients with cardiovascular disease, as well as in patients with prolongation of the QT interval, as strong interactions may occur.

Side effects

Side effects that have been reported in investigations and studies, but have occurred rather rarely, are:

• Upper respiratory tract infection
• Bronchitis
• dizziness
• back pain
• Skin rash
• Hypokalemia

Pregnancy and lactation

Whether or not olodaterol has an effect on the mother-to-be during pregnancy is not yet known due to the lack of studies and the data that depend on them.

However, since the active ingredient is a beta-2 adrenoreceptor agonist and thus exerts a relaxing effect by binding to the beta-2 receptor, application shortly before birth may result in relaxation of the uterine muscles and thus inhibit the birth process. Therefore, its use during pregnancy cannot be recommended for the time being.

Animal studies have now shown that olodaterol and its metabolites can pass into breast milk. Whether this has an effect on the child to be breastfed is pending, as there are no field reports on this yet.

It is assumed, however, that due to the small amount of active ingredient to be taken per day, no effects on the nursing child are to be expected.