Dosing and uses of Stiolto Respimat (tiotropium/olodaterol inhaled)
Adult dosage forms and strengths
tiotropium bromide/olodaterol inhaled
oral inhaler
- (3.124mcg/2.736mcg)/actuation (equivalent to 2.5mcg/2.5mcg)
Chronic Obstructive Pulmonary Disease
Indicated for long-term, once-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema
Inhale 2 actuations PO qDay at the same time of the day
Dosage modifications
Renal impairment
- No dosage adjustment required
- Moderate-to-severe (≤60 mL/min): Monitor closely for anticholinergic adverse effects
Hepatic impairment
- Mild-to-moderate: No dose adjustment required
- Severe: Not studied
Dosing Considerations
Not indicated to treat acute deteriorations of COPd
Not indicated to treat asthma
Pediatric dosage forms and strengths
Safety and efficacy not established
Stiolto Respimat (tiotropium/olodaterol inhaled) adverse (side) effects
Incidence similar to individual components
>10%
Nasopharyngitis (12.4%)
1-10%
Cough (3.9%)
Back pain (3.6%)
≤3%
- Metabolism and nutrition disorders: Dehydration
- Nervous system disorders: Dizziness, insomnia
- Eye disorders: Glaucoma, intraocular pressure increased, vision blurred
- Cardiac/vascular disorders: Atrial fibrillation, palpitations, supraventricular tachycardia, tachycardia, hypertension
- Respiratory, thoracic, and mediastinal disorders: Epistaxis, pharyngitis, dysphonia, bronchospasm, laryngitis, sinusitis
- Gastrointestinal disorders: Dry mouth, constipation, oropharyngeal candidiasis, dysphagia, gastroesophageal reflux disease, gingivitis, glossitis, stomatitis, intestinal obstruction including paralytic ileus
- Skin and subcutaneous disorders: Rash, pruritus, angioneurotic edema, urticaria, skin infection, and skin ulcer, dry skin, hypersensitivity (including immediate reactions)
- Musculoskeletal and connective tissue disorders: Arthralgia, joint swelling
- Renal and urinary disorders: Urinary retention, dysuria, and urinary tract infection
Warnings
Black box warnings
Long-acting beta2-adrenergic agonists (LABAs), such as olodaterol, increase the risk for asthma-related death
A placebo-controlled trial with another LABA (salmeterol) showed an increase in asthma-related deaths; this finding is considered a class effect of all LABAs, including olodateroL
Not to be used as a rescue therapy to treat acute bronchospasm; indicated for COPD maintenance therapy
Safety and efficacy not established in patients with asthma; NOT approved for treatment of asthma
Contraindications
LABAs are contraindicated in patients with asthma without use of a long-term asthma control medication; tiotropium/olodaterol inhaled is not indicated for asthma
Hypersensitivity to tiotropium ipratropium, olodaterol, or other ingredients
Postmarketing experience with tiotropium, immediate hypersensitivity reactions, including angioedema (including swelling of the lips, tongue, or throat), itching, or rash reported; hypersensitivity reactions were also reported in clinical trials with tiotropium/olodaterol inhaled
Cautions
LABAs increase the risk of asthma-related death (see Black box warnings)
Do not initiate in acutely deteriorating COPd
Do not use for relief of acute symptoms; concomitant short-acting beta2 agonists can be used as needed for acute relief
Do not exceed the recommended dose; excessive use, or use in conjunction with other medications containing LABA, can result in clinically significant cardiovascular effects and may be fataL
Immediate hypersensitivity reactions reported; discontinue immediately and consider alternatives if immediate hypersensitivity reactions, including angioedema, bronchospasm, or anaphylaxis, occur (see Contraindications)
Life-threatening paradoxical bronchospasm can occur; discontinue immediately
Caution with cardiovascular or convulsive disorders, thyrotoxicosis, or sensitivity to sympathomimetic drugs
Worsening of narrow-angle glaucoma may occur; instruct patients to consult a physician immediately if this occurs
Worsening of urinary retention may occur; caution with prostatic hyperplasia or bladder-neck obstruction and instruct patients to consult a physician immediately if this occurs
May cause hypokalemia or hyperglycemia
Monitor patients with moderate-to-severe renal impairment (≤60 mL/min) for anticholinergic adverse effects; tiotropium is predominantly excreted renally
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown if distributed in human breast milk
Tiotropium, olodaterol, and metabolites of olodaterol are excreted into the milk of lactating rats
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Stiolto Respimat (tiotropium/olodaterol inhaled)
Mechanism of action
Tiotropium: Long-acting antimuscarinic agent, often referred to as anticholinergic; inhibits M3-receptors at smooth muscle, leading to bronchodilation
Olodaterol: Long-acting beta2-adrenergic agonist (LABA); activates specific beta2-adrenergic receptors on the surface of smooth muscle cells, which increases intracellular cAMP and smooth muscle relaxation
Absorption
Tiotropium
- ~33% of the inhaled dose reaches the systemic circulation
- Absolute bioavailability (oral solution): 2-3%
- Peak plasma time: 5-7 minutes after inhalation
OlodateroL
- ~30% of the inhaled dose reaches the systemic circulation
- Absolute bioavailability (oral solution): <1%
- Peak plasma time: 10-20 minutes after inhalation
Distribution
Tiotropium
- Protein bound: 72%
- Vd: 32 L/kg
OlodateroL
- Protein bound: 60%
- Vd: 1110 L
Metabolism
Tiotropium: 25% metabolized by CYP2D6 and 3A4, then subsequent glutathione conjugation
OlodateroL
- Substantially metabolized by direct glucuronidation and by O-demethylation at the methoxy moiety followed by conjugation
- Cytochrome P450 isozymes CYP2C9 and CYP2C8, with negligible contribution of CYP3A4, are involved in the O-demethylation of olodaterol
- Uridine diphosphate glycosyl transferase isoforms UGT2B7, UGT1A1, 1A7, and 1A9 were shown to be involved in the formation of olodaterol glucuronides
Elimination
Tiotropium
- Half-life (inhaled): 25 hr (terminal)
- Total clearance: 880 mL/min (IV administration)
- Excretion: 18.6% urine; remainder being mainly nonabsorbed drug in the gut that is eliminated via the feces
OlodateroL
- Half-life (inhaled): 45 hr (terminal); 7.5 hr (effective)
- Total clearance: 872 mL/min
- Renal clearance: 173 mL/min
- Excretion: 9% urine; remainder being mainly nonabsorbed drug in the gut that is eliminated via the feces
Administration
Instructions
See prescribing information for full instructions
Priming inhaler
- When using the unit for the first time, insert the cartridge into inhaler and prime the unit by actuating the inhaler toward the ground until an aerosol cloud is visible and then repeat the process 3 more times
- If not used for >3 days, patients are to actuate the inhaler once to prepare the inhaler for use
- If not used for >21 days, patients are to actuate the inhaler until an aerosol cloud is visible and then repeat the process 3 more times to prepare the inhaler for use
Storage
Store at controlled room temperature at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)
Avoid freezing
