tiotropium (Rx)

>10%

Upper respiratory tract infection (41%)

Dry mouth (16%)

Sinusitis (11%)

1-10%

Abdominal pain

Allergic reaction

Angina pectoris (including aggravated angina pectoris)

Cataract

Chest pain (nonspecific)

Constipation

Depression

Dyspepsia

Dysphonia

Edema

Epistaxis

Gastroesophageal reflux

Herpes zoster

Hypercholesterolemia

Hyperglycemia

Infection

Laryngitis

Leg pain

Moniliasis

Myalgia

Paresthesia

Pharyngitis

Rash

Rhinitis

Skeletal pain

Stomatitis (including ulcerative stomatitis)

Urinary tract infection

Vomiting

<1%

Angioedema

Fibrillation

Supraventricular tachycardia

Urinary retention

Postmarketing Reports

Bronchospasm

Glossitis

Dehydration

Insomnia

Contraindications

History of hypersensitivity to ipratropium or tiotropium

History of severe hypersensitivity to milk proteins (excipient in powder contained in capsule)

Lactose allergy

Cautions

Not for acute use; not a rescue medication

Immediate hypersensitivity reactions (eg, angioedema, itching, rash); stop treatment immediately

Capsule not to be swallowed; to be administered only by PO inhalation via HandiHaler device

Worsening of narrow-angle glaucoma

Worsening of urinary retention

Potential for paradoxical bronchospasm

Prostatic hyperplasia

Bladder-neck obstruction

Wash hands after handling capsules

Pregnancy

The limited human data with therapy during pregnancy are insufficient to inform a drug-associated risk of adverse pregnancy-related outcomes

Poorly or moderately controlled asthma in pregnancy increases maternal risk of preeclampsia and infant prematurity, low birth weight, and small for gestational age; level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control

Lactation

There are no data on presence of tiotropium in human milk, effects on breastfed infant, or effects on milk production; tiotropium is present in milk of lactating rats; however, clinical relevance of these data are not clear. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal condition

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.

Mechanism of Action

Long-acting antimuscarinic agent, often referred to as anticholinergic

Inhibits M3-receptors at smooth muscle, leading to bronchodilation

Absorption

Bioavailability: 19.5%

Onset: 30 min

Duration: >24 hr

Time to peak effect: 1-4 hr

Distribution

Protein bound: 72%

Vd: 32 L/kg

Metabolism

Metabolized in liver via CYP450-dependent oxidation and subsequent glutathione conjugation

Elimination

Half-life: 5-6 days

Total body clearance: 880 mL/min

Excretion: Urine

Oral Inhalation

Spiriva Respimat: Premeasured dose in slow-moving mist for oral inhalation; delivers medication in a way that does not depend on how fast air is breathed in from the inhaler

To receive the full dose of medication, Spiriva Respimat must be administered as 2 inhalations once-daily (ie, 2 inhalations of 2.5 mcg [5 mcg] for COPD; 2 inhalations of 1.25 mcg [2.5 mcg] for asthma)

Spiriva Handihaler: Powder for inhalation; device is dependent on the patient's ability to inhale the powder