TOBI

Absorption TOBI contains tobramycin, a cationic polar molecule that does not readily cross epithelial membranes. (1) The bioavailability of TOBI may vary because of individual differences in nebulizer performance and airway pathology. (2) Following administration of TOBI, tobramycin remains concentrated primarily in the airways. Serum Concentrations The average serum concentration of tobramycin one hour after inhalation of a single 300-mg dose of TOBI by cystic fibrosis patients was 0.95 mcg/mL....

Two identically designed, double-blind, randomized, placebo-controlled, parallel group, 24-week clinical studies (Study 1 and Study 2) at a total of 69 cystic fibrosis centers in the United States were conducted in cystic fibrosis patients with P. aeruginosa . Subjects who were less than 6 years of age, had a baseline creatinine of >2 mg/dL, or had Burkholderia cepacia isolated from sputum were excluded. All subjects had baseline FEV 1 % predicted between 25% and 75%. In these clinical studies, 258 patients received TOBI therapy on an outpatient basis (see Table 2) using a hand-held PARI LC PL...

The following serious adverse reactions are described below and elsewhere in the labeling:

• Bronchospasm [see Warnings and Precautions (5.1) ]
• Ototoxicity [see Warnings and Precautions (5.2) ]
• Nephrotoxicity [see Warnings and Precautions (5.3) ]
• Neuromuscular Disorders [see Warnings and Precautions (5.4) ]
• Embryo-fetal Toxicity [see Warnings and Precautions (5.5) ]
• Concomitant Use of Systemic Aminoglycosides [see Warnings and Precautions (5.6) ] Most common adverse reactions (incidenc...

TOBI is contraindicated in patients with a known hypersensitivity to any aminoglycoside. Known hypersensitivity to any aminoglycoside ( 4 )

• Bronchospasm: Can occur with inhalation of TOBI. Treat as medically appropriate, if it occurs. ( 5.1 )
• Ototoxicity: Tinnitus and hearing loss have been reported in patients receiving TOBI. If noted, manage as medically appropriate, including potentially discontinuing TOBI. ( 5.2 )
• Nephrotoxicity: Has been associated with aminoglycosides as a class. If nephrotoxicity develops, manage the patient as medically appropriate, including potentially discontinuing TOBI. ( 5.3 )
• Neuromuscular Diso...

7 DRUG INTERACTIONS

• Concurrent and/or sequential use of TOBI with other drugs with neurotoxic, nephrotoxic, or ototoxic potential should be avoided. ( 7.1 )
• Concomitant administration with ethacrynic acid, furosemide, urea, or intravenous mannitol is not recommended due to possible enhancement of aminoglycoside toxicity. ( 7.2 ) 7.1 Drugs with Neurotoxic, Nephrotoxic or Ototoxic Potential Conc...