STIOLTO RESPIMAT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for STIOLTO RESPIMAT (STIOLTO RESPIMAT).
Dual bronchodilator: tiotropium is a long-acting muscarinic antagonist (LAMA) that inhibits M3 receptors at smooth muscle, causing bronchodilation; olodaterol is a long-acting beta2-adrenergic agonist (LABA) that stimulates beta2 receptors, relaxing airway smooth muscle.
| Metabolism | Tiotropium is minimally metabolized via non-enzymatic ester cleavage and cytochrome P450 (CYP2D6, CYP3A4); olodaterol is metabolized via direct glucuronidation (UGT2B7, UGT1A1, UGT1A9) and O-demethylation via CYP2C8, CYP2C9, with minor contributions from CYP3A4. |
| Excretion | Tiotropium: 14% renal unchanged, remainder as non-renally eliminated metabolites (biliary/fecal). Olodaterol: <1% renal unchanged, 84% fecal as metabolites, 16% renal as metabolites. |
| Half-life | Tiotropium: 5-6 days (terminal). Olodaterol: 17-19 hours (terminal). Clinically, once-daily dosing maintains therapeutic levels. |
| Protein binding | Tiotropium: 34% bound (primarily to albumin). Olodaterol: 60% bound (to albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Tiotropium: 32 L/kg (extensive tissue distribution). Olodaterol: 500 L (approx 7 L/kg for a 70 kg individual, extensive distribution). |
| Bioavailability | Tiotropium: 19.5% (inhalation) versus <1% oral. Olodaterol: 30% (inhalation) versus <1% oral. |
| Onset of Action | Tiotropium: within 30 minutes (peak bronchodilation at 2-3 h). Olodaterol: within 5 minutes (peak at 1-2 h). Inhaled administration. |
| Duration of Action | Tiotropium: >24 hours (bronchodilation maintained over 24 h with once-daily dosing). Olodaterol: 24 hours (bronchodilation maintained over 24 h with once-daily dosing). |
2 inhalations (2.5 mcg tiotropium/2.5 mcg olodaterol per inhalation) once daily via Respimat inhaler.
| Dosage form | SPRAY, METERED |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR 30-89 mL/min). Not recommended for severe renal impairment (GFR <30 mL/min) due to lack of data. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not recommended for severe hepatic impairment (Child-Pugh C) due to lack of data. |
| Pediatric use | Not approved for pediatric use. Safety and efficacy not established in patients under 18 years. |
| Geriatric use | No specific dose adjustment required; use with caution due to potential for increased anticholinergic effects (e.g., urinary retention, constipation). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for STIOLTO RESPIMAT (STIOLTO RESPIMAT).
| Breastfeeding | Unknown whether tiotropium or olodaterol are excreted in human breast milk. Tiotropium is detected in rat milk. Caution should be exercised when administered to a nursing woman. No M/P ratio available. |
| Teratogenic Risk | Tiotropium and olodaterol: No adequate and well-controlled studies in pregnant women. In animal studies, tiotropium bromide showed no evidence of teratogenicity at exposures up to approximately 790 times the maximum recommended human daily inhalation dose. Olodaterol demonstrated no teratogenicity in rats and rabbits at exposures up to 920 and 1800 times the MRHDID, respectively. However, beta-agonists may cause uterine relaxation and delay labor. Use during pregnancy only if potential benefit justifies potential risk to fetus. First trimester: limited data; second and third trimesters: risk of uterine relaxation. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to tiotropium, olodaterol, or any component","Use as monotherapy for asthma (without ICS)"]
| Precautions | ["Not for acute bronchospasm or rescue therapy","LABA use increases risk of asthma-related death (not studied in asthma; contraindicated in asthma without concomitant ICS)","Paradoxical bronchospasm","Cardiovascular effects (e.g., increased heart rate, arrhythmias, QT prolongation)","Hypersensitivity reactions including anaphylaxis, angioedema","Worsening of narrow-angle glaucoma","Urinary retention"] |
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| Fetal Monitoring | Monitor maternal respiratory status (FEV1, oxygen saturation) and symptoms of COPD exacerbation. Monitor fetal heart rate and uterine activity if used near term due to potential beta-agonist effect on uterine relaxation. Assess for maternal adverse effects such as tachycardia, hypokalemia, hyperglycemia. |
| Fertility Effects | No human studies on fertility. In animal studies, tiotropium bromide did not affect fertility in rats at doses up to 0.089 mg/kg/day (approximately 35 times MRHDID). Olodaterol showed no effect on fertility in rats at inhalation doses up to 1.18 mg/kg/day (approximately 900 times MRHDID). Clinical significance unknown. |