Olodaterol

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Aerosol Solution, Inhalation:

Striverdi Respimat: 2.5 mcg/actuation (4 g) [contains benzalkonium chloride, edetate disodium]

Pharmacology

Mechanism of Action

Long acting beta₂-receptor agonist; activates beta₂ airway receptors, resulting in the stimulation of intracellular adenyl cyclase and a subsequent increase in the synthesis of cyclic-3’,5’ adenosine monophosphate (cAMP). Elevated cAMP levels induce bronchodilation by relaxation of airway smooth muscle cells. Has much greater affinity for beta₂-receptors than for beta₁- or beta₃-receptors.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: 1110 L

Metabolism

Direct glucuronidation (UGT2B7, UGT1A1, 1A7, and 1A9) and O-demethylation (primarily CYP2C9 and 2C8)

Excretion

Urine (5% to 7% unchanged); feces

Onset of Action

5 minutes

Time to Peak

10 to 20 minutes

Duration of Action

24 hours

Half-Life Elimination

7.5 hours

Protein Binding

~60%

Use: Labeled Indications

Chronic obstructive pulmonary disease: Long-term maintenance treatment of airflow obstruction in chronic obstructive pulmonary disease, including chronic bronchitis and/or emphysema

Contraindications

Monotherapy (without use of a concomitant inhaled corticosteroid) in the treatment of asthma

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to olodaterol or any component of the formulation.

Documentation of allergenic cross-reactivity for sympathomimetics is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosage and Administration

Dosing: Adult

COPD: Soft mist inhaler: Oral inhalation: Two inhalations once daily (maximum: 2 inhalations per day.)

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral inhalation: Soft mist inhaler: For oral inhalation only; administer at the same time each day. Prime inhaler prior to initial use or if not used for >21 days by pointing inhaler towards ground and actuating until aerosol cloud is seen, then repeat 3 additional times before use. If not used for >3 days (but ≤21 days), actuate once before use. To prepare inhaler for use after priming, refer to manufacturer labeling. When dose is ready to be administered, breathe in slowly through the mouth and press the dose release button; continue to breathe in slowly as long as possible, then hold breath for 10 seconds or for as long as comfortable. Repeat for second inhalation.

Storage

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Avoid freezing. Discard 3 months after cartridge is inserted into inhaler.

Drug Interactions

AtoMOXetine: May enhance the tachycardic effect of Beta2-Agonists. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Atosiban: Beta2-Agonists may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

Beta2-Agonists (Long-Acting): May enhance the adverse/toxic effect of other Beta2-Agonists (Long-Acting). Avoid combination

Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Monitor therapy

Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination

Betahistine: May diminish the therapeutic effect of Beta2-Agonists. Monitor therapy

Caffeine and Caffeine Containing Products: May enhance the adverse/toxic effect of Olodaterol. Caffeine and Caffeine Containing Products may enhance the hypokalemic effect of Olodaterol. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Loop Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination

Methacholine: Beta2-Agonists (Long-Acting) may diminish the therapeutic effect of Methacholine. Management: Hold long-acting beta₂ agonists for 36 hours before methacholine use. Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Theophylline Derivatives: May enhance the adverse/toxic effect of Olodaterol. Theophylline Derivatives may enhance the hypokalemic effect of Olodaterol. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tricyclic Antidepressants: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

Adverse Reactions

>10%:

Respiratory: Nasopharyngitis (11%)

1% to 10%:

Dermatologic: Skin rash (2%)

Genitourinary: Urinary tract infection (3%)

Neuromuscular & skeletal: Back pain (4%), arthralgia (2%)

Respiratory: Bronchitis (5%)

<1%, postmarketing and/or case reports: Asthma-related death, constipation, cough, depression of ST segment on ECG, diarrhea, dizziness, fever, flattened T wave on ECG, hypersensitivity reaction (includes angioedema), hypokalemia (transient), increased serum glucose (high doses), increased diastolic blood pressure, increased pulse, increased systolic blood pressure, malignant neoplasm of lung, paradoxical bronchospasm, pneumonia, prolonged Q-T interval on ECG, rhinorrhea, upper respiratory tract infection

Warnings/Precautions

Concerns related to adverse effects:

• Asthma-related deaths: Monotherapy with a long-acting beta-2 agonist (LABA) is contraindicated in the treatment of asthma. In a large, randomized, placebo-controlled US clinical trial (SMART 2006), salmeterol was associated with an increase in asthma-related deaths (when added to usual asthma therapy); risk is considered a class effect among all LABAs. When LABAs are used in a fixed-dose combination with inhaled corticosteroids, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to inhaled corticosteroids alone. Current guidelines recommend the use of an inhaled corticosteroid before adding a LABA (GINA 2018; NIH/NHLBI 2007). In a more recent multicenter, randomized, double-blinded trial, the use of salmeterol and an inhaled corticosteroid (ie, fluticasone) combined in a single inhaler in a large number of children, adolescent, and adult patients with persistent asthma (non-life-threatening and stable) did not increase the risk of serious asthma-related events compared with fluticasone alone; in addition, patients receiving fluticasone/salmeterol had fewer severe asthma exacerbations compared with patients receiving fluticasone alone (Peters 2016; Stempel 2016a; Stempel 2016b). Olodaterol is not indicated for the treatment of asthma. Available data do not suggest an increased risk of death with use of a LABA in patients with chronic obstructive pulmonary disease (COPD).
• Bronchospasm: Paradoxical bronchospasm that may be life-threatening may occur with use of inhaled beta-2 agonists; this reaction should be distinguished from inadequate response. Discontinue medication immediately if paradoxical bronchospasm occurs and institute alternative therapy.
• Hypersensitivity: Immediate hypersensitivity reactions, including angioedema, may occur; discontinue therapy if patient develops an allergic reaction.
• Serious effects/fatalities: Do not exceed recommended dose or frequency or use with other medications containing LABAs; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease (arrhythmia, coronary insufficiency, hypertension, or hypertrophic obstructive cardiomyopathy); beta-agonists may cause elevation in blood pressure and heart rate. Beta-2 agonists may also produce electrocardiogram (ECG) changes (eg, T-wave flattening, QTc prolongation, ST segment depression).
• COPD: Appropriate use: Do not use for acute bronchospastic episodes of COPD. Do not initiate in patients with significantly worsening or acutely deteriorating COPD. Available data do not suggest an increased risk of death with use of a LABA in patients with COPD.
• Diabetes: Use with caution in patients with diabetes mellitus; beta-2 agonists may increase serum glucose and aggravate preexisting diabetes mellitus and ketoacidosis.
• Hyperthyroidism: Use with caution in patients with hyperthyroidism; may stimulate thyroid activity.
• Hypokalemia: Use with caution in patients with hypokalemia; beta-2 agonists may decrease serum potassium (transient).
• Seizures: Use with caution in patients with seizure disorders; beta-2 agonists may result in CNS stimulation/excitation.

Special populations:

• Pediatric: LABAs, when used as monotherapy, may increase the risk of asthma-related hospitalization in pediatric and adolescent patients. When LABAs are used in a fixed-dose combination with inhaled corticosteroids, data from large clinical trials in adolescents do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to inhaled corticosteroids alone.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Patient information: Patients using inhaled, short-acting beta-2 agonists should be instructed to discontinue routine use of these medications prior to beginning treatment. Short-acting agents should still be provided to patients; however, use should be reserved for symptomatic relief of acute symptoms. Patients must be instructed to seek medical attention in cases in which acute symptoms are not relieved or a previous level of response is diminished. The need to increase frequency of use of short-acting beta-2 agonists may indicate deterioration of COPD, and medical evaluation must not be delayed.

Monitoring Parameters

FEV₁, FVC, and/or other pulmonary function tests; serum potassium, serum glucose; blood pressure, heart rate; CNS stimulation. Monitor for increased use of short-acting beta₂-agonist inhalers; may be marker of a deteriorating condition.

Pregnancy

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies. Beta-agonists have the potential to affect uterine contractility if administered during labor.

Patient Education

What is this drug used for?

• It is used to treat COPD (chronic obstructive pulmonary disease).
• This drug is not to be used to treat intense flare-ups of shortness of breath. Use a rescue inhaler. Talk with the doctor.

Frequently reported side effects of this drug

• Common cold symptoms
• Diarrhea
• Back pain
• Joint pain
• Sore throat
• Stuffy nose

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit
• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat
• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain
• Chest pain
• Fast heartbeat
• Anxiety
• Severe headache
• Severe dizziness
• Passing out
• Vision changes
• Tremors
• Abnormal heartbeat
• Trouble breathing
• Wheezing
• Cough
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.