1 INDICATIONS AND USAGE Tobramycin inhalation solution is indicated for the management of cystic fibrosis in adults and pediatric patients 6 years of age and older with Pseudomonas aeruginosa .

Safety and efficacy have not been demonstrated in patients under the age of 6 years, patients with forced expiratory volume in 1 second (FEV 1 ) <25% or >75% predicted, or patients colonized with Burkholderia cepacia [see Clinical Studies (14) ].

Tobramycin inhalation solution is an aminoglycoside antibacterial indicated for the management of cystic fibrosis in adults and pediatric patients 6 years of age and older with Pseudomonas aeruginosa.

Safety and efficacy have not been demonstrated in patients under the age of 6 years, patients with forced expiratory volume in 1 second (FEV 1 ) <25% or >75% predicted, or patients colonized with Burkholderia cepacia .

6 ADVERSE REACTIONS 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 (incidence >5%) are increased cough, pharyngitis, increased sputum, dyspnea, hemoptysis, decreased lung function, voice alteration, taste perversion and rash.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lifestar Pharma LLC at 1-888-995-4337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Tobramycin inhalation solution was studied in two Phase 3 clinical studies involving 258 cystic fibrosis patients ranging in age from 6 to 48 years.

Patients received tobramycin inhalation solution in alternating periods of 28 days on and 28 days off drug in addition to their standard cystic fibrosis therapy for a total of 24 weeks.

Table 1 lists the percent of patients with selected adverse reactions that occurred in >5% of tobramycin inhalation solution patients during the two Phase 3 studies.

Table 1: Percent of Patients With Selected Adverse Reactions Occurring in > 5% of Tobramycin Inhalation Solution Patients Adverse Reaction Tobramycin Inhalation Solution (n = 258) % Placebo (n = 262) % Cough Increased 46.1 47.3 Pharyngitis 38.0 39.3 Sputum Increased 37.6 39.7 Dyspnea 33.7 38.5 Hemoptysis 19.4 23.7 Lung Function Decreased 1 16.3 15.3 Voice Alteration 12.8 6.5 Taste Perversion 6.6 6.9 Rash 5.4 6.1 1 Includes reported decreases in pulmonary function tests or decreased lung volume on chest radiograph associated with intercurrent illness or study drug administration.

Selected adverse reactions that occurred in less than or equal to 5% of patients treated with tobramycin inhalation solution: Ear and Labyrinth Disorders: Tinnitus Musculoskeletal and Connective Tissue Disorders: Myalgia Infections and Infestations: Laryngitis Voice Alteration and Tinnitus Voice alteration and tinnitus were the only adverse reactions reported by significantly more tobramycin inhalation solution-treated patients.

Thirty- three patients (13%) treated with tobramycin inhalation solution complained of voice alteration compared to 17 (7%) placebo patients.

Voice alteration was more common in the on-drug periods.

Eight patients from the tobramycin inhalation solution group (3%) reported tinnitus compared to no placebo patients.

All episodes were transient, resolved without discontinuation of the tobramycin inhalation solution treatment regimen, and were not associated with loss of hearing in audiograms.

Tinnitus is one of the sentinel symptoms of cochlear toxicity, and patients with this symptom should be carefully monitored for high frequency hearing loss.

The numbers of patients reporting vestibular adverse experiences such as dizziness were similar in the tobramycin inhalation solution and placebo groups.

Changes in Serum Creatinine Nine (3%) patients in the tobramycin inhalation solution group and nine (3%) patients in the placebo group had increases in serum creatinine of at least 50% over baseline.

In all nine patients in the tobramycin inhalation solution group, creatinine decreased at the next visit.

6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of tobramycin inhalation solution.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Ear and Labyrinth Disorders Hearing loss: Some of these reports occurred in patients with previous or concomitant treatment with systemic aminoglycosides.

Patients with hearing loss frequently reported tinnitus.

[see Warnings and Precautions (5.2) ] Skin and Subcutaneous Tissue Disorders Hypersensitivity, pruritus, urticaria, rash Nervous System Disorders Aphonia, dysgeusia Respiratory, Thoracic, and Mediastinal Disorders Bronchospasm [see Warnings and Precautions (5.1) ] oropharyngeal pain Metabolism and Nutrition Disorders Decreased appetite