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Pregnancy Teratogenic Effects Pregnancy Text Continues Below
Category C. No teratogenic effects occurred in the rat at oral doses up to 2 mg/kg (approximately 160 times the maximum recommended human daily inhalation dose in adults on a mg/m 2 basis). In pregnant Dutch rabbits administered oral doses of 1 mg/kg and above (approximately 20 times the maximum recommended human daily inhalation dose in adults based on the comparison of the AUCs), salmeterol xinafoate exhibited fetal toxic effects characteristically resulting from beta-adrenoceptor stimulation; these included precocious eyelid openings, cleft palate, sternebral fusion, limb and paw flexures, and delayed ossification of the frontal cranial bones. No significant effects occurred at an oral dose of 0.6 mg/kg (approximately 10 times the maximum recommended human daily inhalation dose in adults based on comparison of the AUCs). New Zealand White rabbits were less sensitive since only delayed ossification of the frontal cranial bones was seen at oral doses of 10 mg/kg (approximately 1,600 times the maximum recommended human daily inhalation dose on a mg/m 2 basis). Extensive use of other beta-agonists has provided no evidence that these class effects in animals are relevant to use in humans. There are no adequate and well-controlled studies with SEREVENT Inhalation Aerosol in pregnant women. SEREVENT Inhalation Aerosol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Use in Labor and Delivery There are no well-controlled human studies that have investigated effects of salmeterol on preterm labor or labor at term. Because of the potential for beta-agonist interference with uterine contractility, use of SEREVENT Inhalation Aerosol for prevention of bronchospasm during labor should be restricted to those patients in whom the benefits clearly outweigh the risks. Nursing Mothers Plasma levels of salmeterol after inhaled therapeutic doses are very low. In rats, salmeterol xinafoate is excreted in milk. However, since there is no experience with use of SEREVENT Inhalation Aerosol by nursing mothers, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Caution should be exercised when salmeterol xinafoate is administered to a nursing woman. Pediatric Use The safety and effectiveness of SEREVENT Inhalation Aerosol in children younger than 12 years of age have not been established. Geriatric Use Of the total number of patients who received SEREVENT Inhalation Aerosol in all asthma clinical studies, 241 were 65 years of age and older. Geriatric patients (65 years and older) with reversible obstructive airway disease were evaluated in 4 well-controlled studies of 3 weeks’ to 3 months’ duration. Two placebo-controlled, crossover studies evaluated twice-daily
dosing with salmeterol for 21 to 28 days in 45 patients. An additional 75 geriatric patients were treated with salmeterol for 3 months in 2 large parallel-group, multicenter studies. These 120 patients experienced increases in AM and PM PEF and decreases in diurnal variation in PEF
similar to responses seen in the total populations of the 2 latter studies. The adverse event type and frequency in geriatric patients were not different from those of the total populations studied. In 2 large, randomized, double-blind, placebo-controlled 3-month studies involving patients with COPD, 133 patients using SEREVENT Inhalation Aerosol were 65 years and older. These patients experienced similar improvements in FEV1 as observed for patients younger than 65.
No apparent differences in the efficacy and safety of SEREVENT Inhalation Aerosol were observed when geriatric patients were compared with younger patients in asthma and COPD clinical trials. As with other beta2-agonists, however, special caution should be observed when using SEREVENT Inhalation Aerosol in geriatric patients who have concomitant cardiovascular disease that could be adversely affected by this class of drug. Based on available data, no adjustment of salmeterol dosage in geriatric patients is warranted. Page: << Prev | 1 | 2 | 3 | 4 | 5
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