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Olodaterol


General


Pronunciation

(oh loe DA ter ol)


Brand Names: U.S.

  • Striverdi Respimat

Indications


Use: Labeled Indications

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


Contraindications


Monotherapy in the treatment of asthma (ie, use without a concomitant long-term asthma control medication). Note: Olodaterol is not FDA approved for treatment of asthma.

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.


ALERT: U.S. Boxed Warning

Asthma-related death:

Long-acting beta2-adrenergic agonists (LABA) increase the risk of asthma-related death. Data from a large, placebo-controlled US study that compared the safety of another long-acting beta2-adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of LABA, including olodaterol. The safety and efficacy of olodaterol in patients with asthma have not been established. Olodaterol is not indicated for the treatment of asthma.


Dosing and Administration


Dosing: Adult

COPD: Inhalation: Two inhalations once daily (maximum: 2 inhalations per day.)


Dosing: Geriatric

Refer to adult dosing


Dosing: Renal Impairment

No dosage adjustment necessary.


Dosing: Hepatic Impairment

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment: There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied).


Administration

For oral inhalation only. 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.


Dosage Forms/Strengths


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]


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

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

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

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

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

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

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

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

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. 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


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.


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% (Limited to important or life-threatening): Asthma-related death, depression of ST segment on ECG, 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


Warnings/Precautions


Concerns related to adverse effects:

- Asthma-related deaths: [U.S. Boxed Warning]: Long-acting beta2-agonists (LABAs) increase the risk of asthma-related deaths. The safety and efficacy of olodaterol in the treatment of asthma have not been established. In a large, randomized, placebo-controlled U.S. 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. It is unknown if olodaterol increases asthma-related deaths. No data exist associating LABA use with an increased risk of death in patients with COPD.

- Bronchospasm: Rarely, paradoxical, life-threatening bronchospasm may occur with use of inhaled beta2-agonists; distinguish from inadequate response, discontinue medication immediately, institute alternative therapy.

- Hypersensitivity: Hypersensitivity reactions, including angioedema, may occur; discontinue therapy if patient develops an allergic reaction.

Disease-related concerns:

- Cardiovascular disease: Use with caution in patients with cardiovascular disease (arrhythmia, coronary insufficiency, hypertension, or HF); beta-agonists may cause elevation in blood pressure and heart rate. Beta2-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; always prescribe olodaterol with an inhaled short-acting beta2-agonist and educate patient on appropriate use. Do not initiate in patients with significantly worsening or acutely deteriorating COPD. Do not increase the olodaterol dose or frequency beyond what is recommended.

- Diabetes: Use with caution in patients with diabetes mellitus; beta2-agonists may increase serum glucose.

- Hyperthyroidism: Use with caution in patients with hyperthyroidism; may stimulate thyroid activity.

- Hypokalemia: Use with caution in patients with hypokalemia; beta2-agonists may decrease serum potassium.

- Seizure disorders: Use with caution in patients with seizure disorders; beta2-agonists may result in CNS stimulation/excitation.

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.

- LABA: Do not use with other long-acting beta2-agonists; deaths and significant cardiovascular effects have been reported with excessive sympathomimetic use.


Pregnancy Risk Factor

C


Pregnancy Considerations

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


Actions


Pharmacology

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.


Distribution

Vd: 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%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience pharyngitis or rhinitis. Have patient report immediately to prescriber signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), angina, tachycardia, anxiety, severe headache, severe dizziness, tremors, or signs of a severe pulmonary disorder (lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse) (HCAHPS).

- Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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