Olodaterol

Products

Olodaterol was approved in many countries in 2014 as a solution for inhalation (Striverdi). In 2016, a fixed-dose combination with tiotropium bromide was also marketed (Spiolto). Both drugs are administered with the Respimat.

Respimat

The Respimat is a new inhalation device that releases a visible spray, or aerosol. The droplets are fine and move less rapidly than with a metered-dose inhaler. The nebulized solution is also delivered for longer periods of time, making it easier to coordinate when inhaling. Unlike metered dose inhalers and powder inhalers, more active ingredient reaches the lungs and less remains in the mouth and throat. Forceful inhalation is not necessary. The Respimat contains no propellant gas and works purely mechanically, so it contains no battery. The following drugs are approved in many countries:

Striverdi Respimat: olodaterol.
Spiolto Respimat: olodaterol + tiotropium bromide
Spiriva Respimat: tiotropium bromide

Structure and properties

Olodaterol (C₂₁H₂₆N₂O₅, M_r = 386.4 g/mol) is present in the drug as olodaterol hydrochloride, a white powder that is sparingly soluble in water. It is present as a pure -enantiomer and is structurally closely related to formoterol.

Effects

Olodaterol (ATC R03AC19) has bronchodilator and mild anti-inflammatory properties. The effects are due to selective agonism at beta2-adrenoceptors. This stimulates adenylyl cyclases (adenylate cyclases), thereby increasing cyclic adenosine monophosphate (cAMP) formation. cAMP relaxes smooth muscle cells in the airways, mediating bronchodilation. Olodaterol has a rapid onset of action and a long duration of action of at least 24 hours (VLABA, very long-acting β2-agonist).

Indications

For symptomatic long-term treatment of chronic obstructive pulmonary disease (COPD).

Dosage

According to the SmPC. The solution is inhaled once daily and always at the same time of day. One dose includes two sprays. Thus, it must always be inhaled twice in a row.

Contraindications

Hypersensitivity
Asthma
Acute bronchospasm
Use in children and adolescents has not been studied.

Full precautions can be found in the drug label.

Interactions

Drug-drug interactions have been described with the following substances:

Sympathomimetics: Enhancement of adverse effects.
Xanthine derivatives, steroids, and diuretics: Hypokalemia
Beta-blockers: attenuation of effects.
MAO inhibitors, tricyclic antidepressants, agents that prolong the QT interval: cardiovascular side effects.
Potent CYP and P-glycoprotein inhibitors such as ketoconazole: increase in systemic availability.
Other agents that are subsequently inhaled: Increase in availability

Adverse effects

The most common possible adverse effects include inflammation of the nasopharynx (nasopharyngitis), dizziness, and a skin rash. Olodaterol, like other beta2-sympathomimetics, has cardiovascular effects (pulse elevation, blood pressure elevation, ECG changes) and may prolong the QT interval. It may induce paradoxical bronchospasm and lead to hypokalemia and hyperglycemia.