Tiotropium Bromide

Pronunciation: tye-oh-TROE-pee-um BROE-mide
Class: Anticholinergic

Trade Names

Spiriva
- Capsule, powder for inhalation 18 mcg

Pharmacology

Inhibits smooth muscle receptors, leading to bronchodilation.

Pharmacokinetics

Absorption

Bioavailability is approximately 19.5%. T _max is 5 min. At steady state, peak and trough plasma levels are 17 to 19 pg/mL and 3 to 4 pg/mL, respectively.

Distribution

Vd is 32 L/kg. Protein binding is 72%.

Metabolism

CYP2D6 and CYP3A4 are involved.

Elimination

Approximately 14% is eliminated unchanged in the urine; the remainder is not absorbed in the gut and is eliminated in the feces. Terminal elimination half-life is 5 to 6 days.

Special Populations

Renal Function Impairment

Reduced Cl and increased plasma concentrations may occur.

Hepatic Function Impairment

Not studied.

Elderly

Advanced age is associated with a decrease in tiotropium renal Cl, which may be explained by decreased renal function.

Indications and Usage

Long-term maintenance treatment of bronchospasm associated with COPD, including chronic bronchitis and emphysema; to reduce exacerbations in COPD patients.

Contraindications

Hypersensitivity to ipratropium or tiotropium.

Dosage and Administration

Adults

Inhalation 2 inhalations of 1 capsule daily.

General Advice

For inhalation only with the HandiHaler device.
Patients should not swallow capsules.

Storage/Stability

Store at 59° to 86°F. Protect from extreme temperature and moisture. Do not remove capsule from sealed blister until immediately before use. Discard any capsule that is inadvertently removed from the sealed blister and not used immediately. Do not store capsules in inhalation device.

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Angina pectoris, including aggravated angina pectoris (1% to 3%); palpitations, tachycardia (postmarketing).

CNS

Headache (6%); depression, insomnia (4%); dysphonia, paresthesia (1% to 3%); dizziness (postmarketing).

Dermatologic

Rash (4%); dry skin; skin infection; skin ulcer; pruritus, urticaria (postmarketing).

EENT

Pharyngitis (13%); cataract (1% to 3%); oropharyngeal candidiasis; hoarseness, IOP, oral candidiasis, throat irritation (postmarketing).

GI

Dry mouth (16%); dyspepsia (6%); abdominal pain, constipation (5%); vomiting (4%); gastroesophageal reflux, stomatitis (including ulcerative stomatitis) (1% to 3%); gingivitis; dysphagia, intestinal obstruction, including ileus paralytic (postmarketing).

Metabolic-Nutritional

Hypercholesterolemia, hyperglycemia (1% to 3%); dehydration.

Musculoskeletal

Arthralgia, myalgia (4%); skeletal pain (1% to 3%); joint swelling.

Respiratory

Upper respiratory tract infection (41%); sinusitis (11%); rhinitis (6%); epistaxis (4%); coughing (at least 3%); laryngitis (1% to 3%).

Miscellaneous

Accidents (13%); nonspecific chest pain, UTI (7%); dependent edema (5%); infection, moniliasis (4%); arthritis, flu-like symptoms (at least 3%); allergic reaction, herpes zoster infection, leg pain (1% to 3%); application-site irritation (eg, glossitis, mouth ulceration, pharyngolaryngeal pain) (postmarketing).

Precautions

Monitor

Closely monitor patients with a history of hypersensitivity reactions to atropine for similar hypersensitivity reactions to tiotropium. Monitor therapy closely in patients with moderate to severe renal impairment. Monitor patients for signs and symptoms of narrow-angle glaucoma and urinary retention.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hypersensitivity

Immediate hypersensitivity reactions, including angioedema, have been reported. Use with caution in patients with severe hypersensitivity to milk proteins.

Renal Function

Monitor therapy closely in patients with moderate to severe renal impairment.

Special Risk Patients

Use with caution in patients with narrow-angle glaucoma, prostatic hyperplasia, urinary retention, or bladder-neck obstruction.

Acute bronchospasm

Not indicated for initial treatment of acute episodes of bronchospasm.

Bronchospasm

Paradoxical bronchospasm may occur.

Overdosage

Symptoms

Anticholinergic signs and symptoms.

Patient Information

Advise patient to continue taking other medications for same condition as prescribed by health care provider.
Instruct patient on the proper storage, handling, and use of the capsules and inhalation device, referring to the Patient's Instructions for Use instruction sheet included with the medication. Ensure that patient understands how to clean the inhalation device.
Advise patient that medication should never be administered with a spacer device or with any other inhalation device than that provided. Caution patient not to administer other inhaled medications with the inhalation device.
Caution patient not to exceed prescribed dose. Inform patient that medication is being inhaled even if the dose being delivered is not tasted or felt.
Instruct patient not to stop the medication once symptoms have improved. Continued daily use is necessary to control symptoms.
Advise patient not to change the dose or stop using unless advised by health care provider.
Warn patient that tiotropium is a maintenance medication and is not to be used for immediate relief of breathing problems. Advise patient to use rescue medication (short-acting bronchodilator) to obtain rapid relief of breathing problems.
Advise patient that medication does not replace inhaled or oral corticosteroids and to continue to use those drugs as prescribed by health care provider.
Advise patient to inform health care provider if symptoms do not improve or worsen, if more short-acting bronchodilator than usual is needed, or if the short-acting bronchodilator appears to become less effective.
Instruct patient to discontinue use and immediately notify health care provider if eye pain or discomfort, blurred vision, vision halos, or colored images develop in association with red eyes. Advise patient that these symptoms may be associated with a serious problem that will require immediate medical care.
Advise patient to carry medical identification (eg, card, bracelet) indicating that they have COPD.