ler, yet the adults were more likely to discontinue: of the 16 patients on TOBI Podhaler in Study 1 who discontinued treatment due to cough events, 14 were ≥20 years of age, one patient was between the ages of 13 and <20, and one was between the ages of 6 and <13. The rates of bronchospasm (as measured by ≥20% decrease in FEV1 % predicted post-dose) were approximately 5% in both treatment groups, and none of these patients experienced concomitant cough.
In Study 2, cough was the most commonly reported adverse event during the first cycle of treatment (the double blind period of treatment) and occurred more frequently in placebo-treated patients (26.5%) than patients treated with TOBI Podhaler (13%). Similar percentages of patients in both treatment groups reported cough as a baseline symptom. In Study 3, cough events were reported by three patients in the TOBI Podhaler group (10%) and none in the placebo group (0%).
7 DRUG INTERACTIONS
No clinical drug interaction studies have been performed with TOBI Podhaler. In clinical studies, patients receiving TOBI Podhaler continued to take dornase alfa, bronchodilators, inhaled corticosteroids, and macrolides. No clinical signs of drug interactions with these medicines were identified.
Concurrent and/or sequential use of TOBI Podhaler with other drugs with neurotoxic, nephrotoxic, or ototoxic potential should be avoided.
Some diuretics can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue. TOBI Podhaler should not be administered concomitantly with ethacrynic acid, furosemide, urea, or mannitol.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Teratogenic Effects – Pregnancy Category D [see Warnings and Precautions (5.6)]
No reproduction toxicology studies have been conducted with TOBI Podhaler. However, subcutaneous administration of tobramycin at doses of 100 or 20 mg/kg/day during organogenesis was not teratogenic in rats or rabbits, respectively. Doses of tobramycin ≥ 40 mg/kg/day were severely maternally toxic to rabbits and precluded the eva luation of teratogenicity. Ototoxicity was not eva luated in offspring during nonclinical reproduction toxicity studies with tobramycin.
Aminoglycosides can cause fetal harm (e.g., congenital deafness) when administered to a pregnant woman. No adequate and well-controlled studies of TOBI Podhaler in pregnant women have been conducted. If TOBI Podhaler is used during pregnancy, or if the patient becomes pregnant while taking TOBI Podhaler, the patient should be apprised of the potential hazard to the fetus.
8.3 Nursing Mothers
The amount of tobramycin excreted in human breast milk after administration by inhalation is not known. Because of the potential for ototoxicity and nephrotoxicity in infants, a decision should be made whether to terminate nursing or discontinue the drug, taking into account the importance of the drug to the mother.
8.4 Pediatric Use
Patients 6 years and older were included in the Phase 3 studies with TOBI Podhaler; 206 patients below 20 years of age received TOBI Podhaler. No dosage adjustments are needed based on age. The overall pattern of adverse events in pediatric patients was similar to the adults. Dysgeusia (taste disturbance) was more commonly reported in younger patients six to 19 years of age than in patients 20 years and older, 7.4% vs 2.7%, respectively. Safety and effectiveness in pediatric patients below the age of 6 years have not been established |
