Chronic obstructive pulmonary disease, maintenance:
Note: Depending on symptoms and exacerbation risk, may use monotherapy long-acting bronchodilator (long-acting beta agonist or long-acting muscarinic antagonist). In patients with more symptoms (eg, Group B), use in combination with long-acting muscarinic antagonist. In addition, a short-acting bronchodilator is used for intermittent symptom relief (Ref).
Soft mist inhaler (2.5 mcg/actuation): Oral inhalation: 2 inhalations once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
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).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>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 QT interval on ECG, rhinorrhea, upper respiratory tract infection
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.
Concerns related to adverse effects:
• Asthma-related deaths: Monotherapy with a long-acting beta-2 agonist (LABA) is contraindicated in the treatment of asthma. The use of LABAs as monotherapy has been associated with an increased risk of severe exacerbations and asthma-related deaths (SMART [Nelson 2006]; Walters 2007); additional data from other clinical trials suggest risk of asthma-related hospitalization may also be increased with LABA monotherapy in pediatric and adolescent patients. However, data from large, randomized, double-blind controlled trials do not show a significant increase in risk of serious asthma-related events (including hospitalizations, intubations, and death) in adults, adolescents, and pediatric patients (4 to 11 years of age) when fixed-dose LABAs are used with inhaled corticosteroids combined in a single inhaler compared with inhaled corticosteroid monotherapy (FDA 2017). Olodaterol is not indicated for the treatment of asthma.
• 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.
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.
Striverdi Respimat 4 g delivers 60 inhalations (institutional pack delivers 28 inhalations).
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 (edta) disodium]
No
Aerosol solution (Striverdi Respimat Inhalation)
2.5 mcg/ACT (per gram): $80.39
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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.
Chronic obstructive pulmonary disease, maintenance: Long-term maintenance treatment of airflow obstruction in chronic obstructive pulmonary disease, including chronic bronchitis and/or emphysema
Striverdi Respimat may be confused with Strivarga
Substrate of CYP2C8 (Minor), CYP2C9 (Minor), CYP3A4 (Minor), UGT1A1, UGT1A7, UGT1A9, UGT2B7; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Atazanavir: May increase serum concentration of UGT1A1 Substrates. Management: Do not use UGT1A1 substrates for which small increases in exposure can cause serious adverse effects together with atazanavir, and use caution with any UGT1A1 substrate, even when small changes in exposure are less likely to cause serious adverse effects. Risk D: Consider Therapy Modification
Atomoxetine: May increase hypertensive effects of Sympathomimetics. Atomoxetine may increase tachycardic effects of Sympathomimetics. Risk C: Monitor
Atomoxetine: May increase tachycardic effects of Beta2-Agonists. Atomoxetine may increase hypertensive effects of Beta2-Agonists. Risk C: Monitor
Atosiban: Beta2-Agonists may increase adverse/toxic effects of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Risk C: Monitor
Belumosudil: May increase serum concentration of UGT1A1 Substrates. Management: Avoid coadministration of belumosudil with substrates of UGT1A1 for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the UGT1A1 substrate may be required. Risk D: Consider Therapy Modification
Beta-Blockers (Beta1 Selective): May decrease bronchodilatory effects of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Risk C: Monitor
Beta-Blockers (Nonselective): May decrease bronchodilatory effects of Beta2-Agonists. Risk X: Avoid
Beta2-Agonists (Long-Acting): May increase adverse/toxic effects of Beta2-Agonists (Long-Acting). Risk X: Avoid
Bornaprine: Sympathomimetics may increase anticholinergic effects of Bornaprine. Risk C: Monitor
Caffeine and Caffeine Containing Products: May increase adverse/toxic effects of Olodaterol. Caffeine and Caffeine Containing Products may increase hypokalemic effects of Olodaterol. Risk C: Monitor
Cannabinoid-Containing Products: May increase tachycardic effects of Sympathomimetics. Risk C: Monitor
Cocaine (Topical): May increase hypertensive effects 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. Risk D: Consider Therapy Modification
Dihydralazine: Sympathomimetics may decrease therapeutic effects of Dihydralazine. Risk C: Monitor
Doxofylline: Sympathomimetics may increase adverse/toxic effects of Doxofylline. Risk C: Monitor
Esketamine (Injection): May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for elevated heart rate, hypertension, and arrhythmias may be increased. Risk C: Monitor
Guanethidine: May increase hypertensive effects of Sympathomimetics. Guanethidine may increase arrhythmogenic effects of Sympathomimetics. Risk C: Monitor
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor
Kratom: May increase adverse/toxic effects of Sympathomimetics. Risk X: Avoid
Levothyroxine: May increase therapeutic effects of Sympathomimetics. Sympathomimetics may increase therapeutic effects of Levothyroxine. Levothyroxine may increase adverse/toxic effects of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Risk C: Monitor
Linezolid: May increase hypertensive effects of Sympathomimetics. Management: Consider initial dose reductions of sympathomimetic agents, and closely monitor for enhanced blood pressure elevations, in patients receiving linezolid. Risk D: Consider Therapy Modification
Loop Diuretics: Beta2-Agonists may increase hypokalemic effects of Loop Diuretics. Risk C: Monitor
Loxapine: Agents to Treat Airway Disease may increase adverse/toxic effects 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. Risk X: Avoid
Methacholine: Beta2-Agonists (Long-Acting) may decrease therapeutic effects of Methacholine. Management: Hold long-acting beta2 agonists for 36 hours before methacholine use. Risk D: Consider Therapy Modification
Mitapivat: May decrease serum concentration of UGT1A1 Substrates. Risk C: Monitor
Monoamine Oxidase Inhibitors: May increase adverse/toxic effects of Beta2-Agonists. Risk C: Monitor
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects 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. Risk C: Monitor
Solriamfetol: Sympathomimetics may increase hypertensive effects of Solriamfetol. Sympathomimetics may increase tachycardic effects of Solriamfetol. Risk C: Monitor
Sympathomimetics: May increase adverse/toxic effects of Sympathomimetics. Risk C: Monitor
Tedizolid: May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for increased blood pressure and heart rate may be increased. Risk C: Monitor
Theophylline Derivatives: May increase hypokalemic effects of Beta2-Agonists. Beta2-Agonists may increase adverse/toxic effects of Theophylline Derivatives. Specifically, sympathomimetic effects may be increased. Risk C: Monitor
Thiazide and Thiazide-Like Diuretics: Beta2-Agonists may increase hypokalemic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor
Tricyclic Antidepressants: May increase adverse/toxic effects of Beta2-Agonists. Risk C: Monitor
Adverse events were observed in some animal reproduction studies. Beta-agonists have the potential to affect uterine contractility if administered during labor.
It is not known if olodaterol is present in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
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.
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.
Onset of action: 5 minutes
Duration: 24 hours
Distribution: Vd: 1110 L
Protein binding: ~60%
Metabolism: Direct glucuronidation (UGT2B7, UGT1A1, 1A7, and 1A9) and O-demethylation (primarily CYP2C9 and 2C8)
Bioavailability: 30% (inhalation)
Half-life elimination: 7.5 hours
Time to peak: 10 to 20 minutes
Excretion: Urine (5% to 7% unchanged); feces