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. |
| Molecular Weight | 472.4 |
| Action Class | Anticholinergic Bronchodilator |
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 | Limited human data; animal studies show no teratogenicity at therapeutic doses. Use only if clearly needed. |
| 2nd trimester | Limited human data; no known fetal risk. Use only if clearly needed. |
| 3rd trimester | Limited human data; consider potential for uterine relaxation. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for SPIRIVA (SPIRIVA).
| Placental transfer | Minimal placental transfer due to low systemic bioavailability after inhalation; high molecular weight and quaternary ammonium structure limit transfer. |
| Breastfeeding | Inhaled tiotropium is minimally absorbed systemically; levels in breast milk are likely very low. Not expected to cause adverse effects in nursing infants. |
| Lactation Rating |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Dry mouth, Pharyngitis, Sinusitis, Upper respiratory tract infection, Constipation, Cough, Headache |
| Serious Effects | Paradoxical bronchospasm, Immediate hypersensitivity reactions (angioedema, urticaria, rash, pruritus), Worsening of narrow-angle glaucoma, Urinary retention (especially in patients with prostatic hyperplasia or bladder-neck obstruction), Anticholinergic toxicity (confusion, hallucinations, delirium) in elderly or susceptible patients |
Hypersensitivity to tiotropium or any component of the productHypersensitivity to atropine or its 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. |
Loading safety data…
| L1 (Safe) |
| 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. |
| 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. |
| Food/Dietary | No specific food interactions. Avoid grapefruit juice if also taking medications metabolized by CYP3A4 (tiotropium is minimally metabolized, but caution advised). |
| Clinical Pearls | Spiriva (tiotropium) is a long-acting muscarinic antagonist (LAMA) for maintenance treatment of COPD and asthma. Onset of bronchodilation is within 30 minutes, peak effect at 3 hours, duration >24 hours. Use with caution in narrow-angle glaucoma, prostatic hyperplasia, or bladder-neck obstruction. Do not use for acute bronchospasm. Capsules are for inhalation via HandiHaler only; not for oral use. |
| Patient Advice | Do not swallow capsules; use only with the HandiHaler device. · Rinse mouth after inhalation to reduce risk of dry mouth and thrush. · Use once daily at the same time each day; do not use more than 1 capsule per day. · Seek immediate medical help if you have wheezing, chest tightness, or trouble breathing after use. · Avoid getting powder in eyes; if contact occurs, rinse eyes with water and consult doctor if vision changes or eye pain occur. · Store capsules at room temperature away from moisture; keep in blister pack until use. |