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Spiriva (Tiotropium Bromide Monohydrate Inhalation) - Warnings and Precautions

 
 



WARNINGS

SPIRIVA HandiHaler (tiotropium bromide inhalation powder) is intended as a once-daily maintenance treatment for COPD and is not indicated for the initial treatment of acute episodes of bronchospasm, i.e., rescue therapy.

Immediate hypersensitivity reactions, including angioedema (including swelling of the lips, tongue or throat), itching, and rash may occur after administration of SPIRIVA HandiHaler. If such a reaction occurs, therapy with SPIRIVA HandiHaler should be stopped at once and alternative treatments should be considered.

Inhaled medicines, including SPIRIVA HandiHaler, may cause paradoxical bronchospasm. If this occurs, treatment with SPIRIVA HandiHaler should be stopped and other treatments considered.

PRECAUTIONS

General

As an anticholinergic drug, SPIRIVA HandiHaler (tiotropium bromide inhalation powder) may potentially worsen symptoms and signs associated with narrow-angle glaucoma, prostatic hyperplasia or bladder-neck obstruction and should be used with caution in patients with any of these conditions.

As a predominantly renally excreted drug, patients with moderate to severe renal impairment (creatinine clearance of ≤50 mL/min) treated with SPIRIVA HandiHaler should be monitored closely (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations, Renally-impaired Patients ).

Information for Patients

It is important for patients to understand how to correctly administer SPIRIVA capsules using the HandiHaler device (see Patient’s Instructions for Use). SPIRIVA capsules should only be administered via the HandiHaler device and the HandiHaler device should not be used for administering other medications. The contents of SPIRIVA capsules are for oral inhalation only and must not be swallowed.

SPIRIVA capsules should always be stored in sealed blisters. Remove only one SPIRIVA capsule immediately before use, or its effectiveness may be reduced. Additional SPIRIVA capsules that are exposed to air (i.e., not intended for immediate use) should be discarded.

Eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema may be signs of acute narrow-angle glaucoma. Should any of these signs and symptoms develop, consult a physician immediately. Miotic eye drops alone are not considered to be effective treatment.

Care must be taken not to allow the powder to enter into the eyes as this may cause blurring of vision and pupil dilation.

SPIRIVA HandiHaler is a once-daily maintenance bronchodilator and should not be used for immediate relief of breathing problems, i.e., as a rescue medication.

Drug Interactions

SPIRIVA HandiHaler has been used concomitantly with other drugs commonly used in COPD without increases in adverse drug reactions. These include short-acting and long-acting sympathomimetic (beta-agonists) bronchodilators, methylxanthines, and oral and inhaled steroids. However, the co-administration of SPIRIVA HandiHaler with other anticholinergic-containing drugs (e.g., ipratropium) has not been studied and is therefore not recommended.

Drug/Laboratory Test Interactions

None known.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of tumorigenicity was observed in a 104-week inhalation study in rats at tiotropium doses up to 0.059 mg/kg/day, in an 83-week inhalation study in female mice at doses up to 0.145 mg/kg/day, and in a 101-week inhalation study in male mice at doses up to 0.002 mg/kg/day. These doses correspond to 25, 35, and 0.5 times the Recommended Human Daily Dose (RHDD) on a mg/m2 basis, respectively. These dose multiples may be over-estimated due to difficulties in measuring deposited doses in animal inhalation studies.

Tiotropium bromide demonstrated no evidence of mutagenicity or clastogenicity in the following assays: the bacterial gene mutation assay, the V79 Chinese hamster cell mutagenesis assay, the chromosomal aberration assays in human lymphocytes in vitro and mouse micronucleus formation in vivo, and the unscheduled DNA synthesis in primary rat hepatocytes in vitro assay.

In rats, decreases in the number of corpora lutea and the percentage of implants were noted at inhalation tiotropium doses of 0.078 mg/kg/day or greater (approximately 35 times the RHDD on a mg/m2 basis). No such effects were observed at 0.009 mg/kg/day (approximately 4 times than the RHDD on a mg/m2 basis). The fertility index, however, was not affected at inhalation doses up to 1.689 mg/kg/day (approximately 760 times the RHDD on a mg/m2 basis). These dose multiples may be over-estimated due to difficulties in measuring deposited doses in animal inhalation studies.

Pregnancy

Pregnancy Category C.

No evidence of structural alterations was observed in rats and rabbits at inhalation tiotropium doses of up to 1.471 and 0.007 mg/kg/day, respectively. These doses correspond to approximately 660 and 6 times the recommended human daily dose (RHDD) on a mg/m2 basis. However, in rats, fetal resorption, litter loss, decreases in the number of live pups at birth and the mean pup weights, and a delay in pup sexual maturation were observed at inhalation tiotropium doses of ≥0.078 mg/kg (approximately 35 times the RHDD on a mg/m2 basis). In rabbits, an increase in post-implantation loss was observed at an inhalation dose of 0.4 mg/kg/day (approximately 360 times the RHDD on a mg/m2 basis). Such effects were not observed at inhalation doses of 0.009 and up to 0.088 mg/kg/day in rats and rabbits, respectively. These doses correspond to approximately 4 and 80 times the RHDD on a mg/m2 basis, respectively. These dose multiples may be over-estimated due to difficulties in measuring deposited doses in animal inhalation studies.

There are no adequate and well-controlled studies in pregnant women. SPIRIVA HandiHaler should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Use in Labor and Delivery

The safety and effectiveness of SPIRIVA HandiHaler has not been studied during labor and delivery.

Nursing Mothers

Clinical data from nursing women exposed to tiotropium are not available. Based on lactating rodent studies, tiotropium is excreted into breast milk. It is not known whether tiotropium is excreted in human milk, but because many drugs are excreted in human milk and given these findings in rats, caution should be exercised if SPIRIVA HandiHaler is administered to a nursing woman.

Pediatric Use

SPIRIVA HandiHaler is approved for use in the maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease, including chronic bronchitis and emphysema. This disease does not normally occur in children. The safety and effectiveness of SPIRIVA HandiHaler in pediatric patients have not been established.

Geriatric Use

Of the total number of patients who received SPIRIVA HandiHaler in the 1-year clinical trials, 426 were <65 years, 375 were 65–74 years and 105 were ≥75 years of age. Within each age subgroup, there were no differences between the proportion of patients with adverse events in the SPIRIVA HandiHaler and the comparator groups for most events. Dry mouth increased with age in the SPIRIVA HandiHaler group (differences from placebo were 9.0%, 17.1%, and 16.2% in the aforementioned age subgroups). A higher frequency of constipation and urinary tract infections with increasing age was observed in the SPIRIVA HandiHaler group in the placebo-controlled studies. The differences from placebo for constipation were 0%, 1.8%, and 7.8% for each of the age groups. The differences from placebo for urinary tract infections were –0.6%, 4.6% and 4.5%. No overall differences in effectiveness were observed among these groups. Based on available data, no adjustment of SPIRIVA HandiHaler dosage in geriatric patients is warranted.

Page last updated: 2009-03-18

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