Olodaterol: Mode of Action as a Long-Acting Beta 2 Agonist

Olodaterol (brand name Striverdi Respimat) is a long-acting beta 2 sympathomimetic (LABA) for once-daily inhalation in chronic obstructive pulmonary disease (COPD). The substance was approved in Europe in 2013 and has become established as an ultra LABA with a duration of action of 24 hours. Olodaterol belongs to a class of modern bronchodilators administered only once daily, simplifying patient use compared to older twice-daily substances such as formoterol or salmeterol. In Germany, olodaterol is available as a monotherapy and in fixed combination with the long-acting anticholinergic tiotropium (Spiolto Respimat).

In clinical trials, olodaterol has demonstrated bronchodilator efficacy and safety in moderate to very severe COPD. The combination with tiotropium showed in the TONADO and OTEMTO studies that dual bronchodilation is superior to monotherapy with either substance and reduces the frequency of exacerbations. Olodaterol is not approved for asthma because monotherapy with a long-acting beta 2 agonist without inhaled corticosteroid is contraindicated in asthma.

Mechanism of Action

Olodaterol is a long-acting selective beta 2 adrenergic receptor agonist with high selectivity for beta 2 receptors over beta 1 receptors. Through activation of beta 2 receptors on smooth bronchial muscle, the intracellular cAMP concentration is increased, leading to activation of protein kinase A and ultimately to relaxation of smooth muscle cells. This results in bronchodilation with widening of the airways and improvement of airflow rates.

Pharmacologically, olodaterol demonstrates rapid onset of action within 5 to 10 minutes and a duration of action of 24 hours, enabling once-daily inhalation. Beta 2 selectivity is even more pronounced compared to albuterol or formoterol, reducing cardiac adverse effects. However, at higher doses or in patients with pre-existing cardiac disease, beta 1-mediated effects such as tachycardia may still occur.

Pharmacokinetically, olodaterol is rapidly absorbed after inhalation. Systemic bioavailability is approximately 30 percent. The elimination half-life is 45 hours, so the intracellular effect lasts considerably longer than the plasma half-life. Olodaterol is metabolized hepatically via CYP2C9 and to a lesser extent CYP2C8, with excretion occurring primarily renally.

Indications

• Maintenance therapy of chronic obstructive pulmonary disease (COPD) in adults from GOLD stage 2 for sustained bronchodilation and symptom reduction
• Combination therapy with tiotropium (Spiolto Respimat) in moderate to very severe COPD for dual bronchodilation
• Improvement of exercise capacity in COPD patients with significant dyspnea on exertion

Olodaterol is not suitable for acute treatment of sudden dyspnea or exacerbation. In these situations, short-acting bronchodilators such as albuterol or ipratropium are used. Olodaterol is not approved for asthma.

Dosage and Administration

Adults with COPD: 5 micrograms once daily, corresponding to 2 puffs from the Respimat inhaler at the same time each day, preferably in the morning.

Combination with tiotropium (Spiolto Respimat): 2 puffs once daily.

Administration: use is with the Respimat Soft Mist inhaler, which produces a special spray technique with fine droplets. On first use, the cartridge must be inserted and the inhaler activated by several puffs.

Inhalation: sit upright, exhale, place mouthpiece between teeth without biting, when triggering inhale slowly and deeply, hold breath for approximately 10 seconds. After inhalation rinse mouth with water.

Renal impairment: no dose adjustment required for moderate impairment. Use with caution in severe impairment. Hepatic impairment: no dose adjustment for moderate impairment. Use with caution in severe impairment.

Important: if COPD worsens or exacerbation occurs, do not increase olodaterol, but follow treatment plan with additional treatment using short-acting bronchodilators or systemic corticosteroids.

Adverse Effects

Common: nasopharyngitis, cough, dizziness, headache, hypertension, tachycardia, palpitations, tremor, dry mouth.

Uncommon: paradoxical bronchospasm (very rare but life-threatening), atrial fibrillation, rash, pruritus, urticaria, hoarseness.

Rare: hypokalemia (especially in combination with other potassium-lowering substances), hyperglycemia, sleep disturbances, allergic reactions including anaphylaxis.

Very rare: acute narrow-angle glaucoma, urinary retention, hypotension.

In case of overdose: pronounced tachycardia, tremor, hypertension or hypotension, hyperglycemia, hypokalemia, nausea. Treatment is symptomatic and supportive with cardiac beta blockers (cautiously due to risk of bronchospasm).

Note: with systemic beta-sympathomimetic effects such as tremor and tachycardia, the selectivity of olodaterol is higher than with short-acting beta 2 agonists, so adverse effects are usually mild.

Drug Interactions

• Other beta-sympathomimetics: additive effects with increased risk of cardiovascular adverse effects, avoid concomitant use of multiple long-acting beta agonists.
• Beta blockers: antagonistic effect, additive risk of bronchospasm especially with non-selective beta blockers. Avoidance or caution with cardioselective beta blockers.
• Diuretics (loop and thiazide diuretics): enhanced hypokalemia.
• Systemic corticosteroids: additional hypokalemia and hyperglycemia.
• Methylxanthines such as theophylline: additive hypokalemia and cardiac effect.
• MAO inhibitors and tricyclic antidepressants: enhanced cardiovascular effect. Caution or avoidance.
• Anesthetics based on halothane or sevoflurane: increased cardiac sensitivity, caution with perioperative use.

Special Precautions

Pregnancy: only with strict indication because limited data are available. Use is possible with demonstrated benefit. Nursing: limited data on passage into breast milk, individual benefit-risk assessment.

Children: not approved because COPD does not occur in childhood. Olodaterol is not indicated for asthma therapy in children or adolescents.

Contraindications: asthma as sole disease (monotherapy without ICS), known hypersensitivity to olodaterol or Atrovent, severe cardiovascular disease such as recent myocardial infarction or unstable angina, severe tachyarrhythmias.

Before therapy: history of cardiovascular disease, thyroid overfunction, diabetes, hypokalemia. Pulmonary function to assess COPD severity. Training in use of Respimat inhaler.

During therapy: regular clinical follow-up, pulmonary function, potassium and glucose in at-risk profile, monitoring for cardiac symptoms. Reevaluate therapy if worsening occurs.

In acute dyspnea: olodaterol not for acute treatment. Patients must be equipped with a short-acting bronchodilator (albuterol spray) for such situations.

Lifestyle: smoking cessation is the most important measure in COPD, physical activity as tolerated, breathing exercises, vaccinations (pneumococcal, influenza, RSV in at-risk profile), avoidance of irritants.

Fitness to drive: generally not impaired. Use caution if dizziness or vision disturbances occur.

You May Also Be Interested In

• Tiotropium, long-acting anticholinergic in COPD
• Glycopyrronium, another long-acting anticholinergic
• Salmeterol, long-acting beta 2 agonist
• Formoterol, long-acting beta 2 agonist
• Salbutamol, short-acting beta 2 agonist as rescue medication

Frequently Asked Questions

Sources

• Gelbe Liste, Olodaterol active ingredient profile
• BfArM, Federal Institute for Drugs and Medical Devices
• German Society for Pneumology and Respiratory Medicine
• AWMF S2k Guideline on Diagnosis and Therapy of COPD
• European Medicines Agency, EPAR Striverdi and Spiolto Respimat