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There have been reports of acute overdosage in pediatric patients in post-marketing experience and clinical studies of up to at least 150 mg/ day with SINGULAIR. The clinical and laboratory findings observed were consistent with the safety profile in adults and older pediatric patients. There were no adverse experiences reported in the majority of overdosage reports. The most frequent adverse experiences observed were thirst, somnolence, mydriasis, hyperkinesia, and abdominal pain. It is not known whether montelukast is removed by peritoneal dialysis or hemodialysis.Drug Interactions SINGULAIR has been administered with other therapies routinely used in the prophylaxis and chronic treatment of asthma with no apparent increase in adverse reactions. In drug-interaction studies, the recommended clinical dose of montelukast did not have clinically important effects on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (norethindrone 1 mg/ ethinyl estradiol 35 mcg), terfenadine, digoxin, and warfarin. Although additional specific interaction studies were not performed, SINGULAIR was used concomitantly with a wide range of commonly prescribed drugs in clinical studies without evidence of clinical adverse interactions. These medications included thyroid hormones, sedative hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, and decongestants. Phenobarbital, which induces hepatic metabolism, decreased the AUC of montelukast approximately 40% following a single 10-mg dose of montelukast. No dosage adjustment for SINGULAIR is recommended. It is reasonable to employ appropriate clinical monitoring when potent cytochrome P450 enzyme inducers, such as phenobarbital or rifampin, are co-administered with SINGULAIR. Text Continues Below
Carcinogenesis, Mutagenesis, Impairment of Fertility No evidence of tumorigenicity was seen in either a 2-year carcinogenicity study in Sprague-Dawley rats at oral gavage doses up to 200 mg/ kg/ day (estimated exposure was approximately 90 times the area under the plasma concentration versus time curve (AUC) for adults and children at the maximum recommended daily oral dose) or in a 92-week carcinogenicity study in mice at oral gavage doses up to 100 mg/ kg/ day (estimated exposure was approximately 30 times the AUC for adults and children at the maximum recommended daily oral dose). Montelukast demonstrated no evidence of mutagenic or clastogenic activity in the following assays: the microbial mutagenesis assay, the V-79 mammalian cell mutagenesis assay, the alkaline elution assay in rat hepatocytes, the chromosomal aberration assay in Chinese hamster ovary cells, and in the in vivo mouse bone marrow chromosomal aberration assay. Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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