The combination tiotropiumolodaterol (brand name, Stiolto RespimatBoehringer Ingelheim) is a LAMA/LABA inhalation spray that maximizes bronchodilation for the long-term, maintenance treatment of COPD. Tiotropium is a LAMA (long-acting muscarinic antagonist) bronchodilator, and olodaterol is a LABA (long-acting beta2-agonist) bronchodilator.

Manifestations of COPD include chronic bronchitis and emphysema.

How does tiotropium-olodaterol work?

Tiotropium is a long-acting muscarinic antagonist, also known as anticholinergic. It connects to the muscarinic receptors subtypes M1 to M5. The M3 receptors are located in the smooth muscles of the bronchi, and are responsible for bronchoconstriction. As tiotropium has affinity to the M3 receptors, it works by blocking their actions on these muscles, leading to bronchodilation.

Olodaterol is a selective LABA, and its effects are due to the stimulation of an enzyme, called adenyl cyclase, in lung muscle cells. This enzyme helps convert adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). When the levels of cAMP increase, smooth muscle cells of the airways relax, inhibiting the release of mediators of immediate hypersensitivity from mast cells.

Beta2-receptors are predominant in the muscle cells of the lungs, but they are also present in heart cells, which means olodaterol may have cardiac effects, such as an irregular heartbeat.

Studies of tiotropium-olodaterol

U.S. Food and Drug Administration (FDA) approval of Stiolto Respimat, in May 2015, was based on the results of the pivotal Phase 3 TONADO 1 and 2 studies (NCT01431274 and NCT01431287). More than 5,000 people with COPD participated in these studies, and results showed that the combination significantly improved patients’ lung function relative to the tiotropium or olodaterol alone. Results also showed that the tiotropium–olodaterol combination has a safety profile similar to either drug alone.

Indications and side effects

Stiolto, the drug combination, is administered using the propellant-free platform inhaler, Respimat, from Boehringer Ingelheim. The Respimat inhaler is designed to deliver a mist, once daily, that a patient can breath in naturally to carry the medication deep into the lungs. As a long-term maintenance treatment, Stiolto Respimat should not be used to treat sudden breathing problems and does not replace a short-acting bronchodilator.

LABA medications like olodaterol are not intended for use by people with asthma, as studies have found that these medications increase the risk of severe worsening of asthma.  It is not known yet whether LABA medicines carry the same risk for people with COPD.

The most common side effects of tiotropium and olodaterol can include a stuffy nose, sinus pain, cough, or back pain. Seek medical help immediately if you show signs of an allergic reaction to the combination (hives, swelling around the face, tongue, lips or throat, etc.), new COPD symptoms appear or existing ones worsen, or other more severe reactions are evident.

There is no generic available.

 

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