SPIRIVA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SPIRIVA (SPIRIVA).
Tiotropium is a long-acting muscarinic antagonist (LAMA) that blocks M3 receptors in the airways, inhibiting acetylcholine-induced bronchoconstriction and mucus secretion.
| Metabolism | Tiotropium is minimally metabolized via cytochrome P450 isoenzymes (mainly CYP3A4 and CYP2D6) and esterase-mediated hydrolysis, with majority excreted unchanged in urine. |
| Excretion | Renal excretion accounts for approximately 60% (mainly as unchanged drug) following intravenous administration; biliary/fecal excretion accounts for about 30% (as non-absorbed drug after oral inhalation). Less than 20% is metabolized via ester hydrolysis (nonspecific esterases) to inactive metabolites. |
| Half-life | Terminal elimination half-life is 27–46 hours (mean ~30 hours) after inhalation. The long half-life supports once-daily dosing due to sustained bronchodilation. |
| Protein binding | Approximately 72% bound to plasma proteins (primarily albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | 32 L/kg (indicating extensive tissue distribution; high Vd due to lipophilicity and tissue binding). |
| Bioavailability | Oral inhalation: ~20% (fraction reaching systemic circulation; most of the inhaled dose is swallowed and undergoes negligible oral absorption due to low bioavailability). |
| Onset of Action | Inhalation: 30 minutes; peak bronchodilation at 3 hours. |
| Duration of Action | 24 hours (bronchodilation maintained over 24 hours with once-daily dosing); clinical effect persists up to 36 hours. |
18 mcg inhalation via HandiHaler once daily, or 2.5 mcg (2 puffs) via Respimat inhaler once daily.
| Dosage form | POWDER |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. For severe impairment (CrCl <30 mL/min), use only if benefit outweighs risk; monitor for anticholinergic effects. |
| Liver impairment | No dosage adjustment required for mild to moderate hepatic impairment. Not studied in severe hepatic impairment; use with caution. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | No specific dosage adjustment; monitor for anticholinergic side effects (e.g., dry mouth, constipation, urinary retention) due to age-related decreased renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SPIRIVA (SPIRIVA).
| Breastfeeding | Caution is advised. Tiotropium is excreted into rat milk; it is not known whether it is excreted into human milk. No M/P ratio available. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for SPIRIVA. |
| Teratogenic Risk | Pregnancy Category C. No adequate studies in pregnant women. In animal studies, tiotropium bromide showed no teratogenic effects at inhalation doses up to 1.4 times the maximum recommended human daily inhalation dose (MRHDID) in rats and rabbits. However, increased post-implantation loss and reduced fetal weights were observed at maternally toxic doses. Risk cannot be ruled out; use only if clearly needed. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to tiotropium bromide or any component of the formulation.","Hypersensitivity to ipratropium or atropine derivatives."]
| Precautions | ["Not for acute bronchospasm or initial therapy of acute exacerbations.","Immediate hypersensitivity reactions (e.g., angioedema, urticaria) may occur.","Paradoxical bronchospasm may occur.","Use caution in patients with narrow-angle glaucoma, urinary retention, or prostatic hyperplasia.","Renal impairment may increase systemic exposure; monitor in moderate to severe impairment."] |
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| Fetal Monitoring | Monitor maternal respiratory status, including peak flow or FEV1 if applicable. No specific fetal monitoring required beyond standard prenatal care. Monitor for signs of anticholinergic toxicity (e.g., dry mouth, constipation, urinary retention) in the mother. |
| Fertility Effects | No human data on fertility. In animal studies, no impairment of fertility was observed in male and female rats at inhalation doses up to 2.9 times the MRHDID. |