5 WARNINGS AND PRECAUTIONS
5.1 Ototoxicity
Caution should be exercised when prescribing TOBI Podhaler to patients with known or suspected auditory or vestibular dysfunction.

Ototoxicity, as measured by complaints of hearing loss or tinnitus, was reported by patients in the TOBI Podhaler clinical studies [see Adverse Reactions (6.1)]. Tinnitus may be a sentinel symptom of ototoxicity, and therefore the onset of this symptom warrants caution. Ototoxicity, manifested as both auditory (hearing loss) and vestibular toxicity, has been reported with parenteral aminoglycosides. Vestibular toxicity may be manifested by vertigo, ataxia or dizziness.
5.2 Nephrotoxicity
Caution should be exercised when prescribing TOBI Podhaler to patients with known or suspected renal dysfunction.

Nephrotoxicity was not observed during TOBI Podhaler clinical studies but has been associated with aminoglycosides as a class.
5.3 Neuromuscular Disorders
Caution should be exercised when prescribing TOBI Podhaler to patients with known or suspected neuromuscular dysfunction.

TOBI Podhaler should be used cautiously in patients with neuromuscular disorders, such as myasthenia gravis or Parkinson’s disease, since aminoglycosides may aggravate muscle weakness because of a potential curare-like effect on neuromuscular function.
5.4 Bronchospasm
Bronchospasm can occur with inhalation of TOBI Podhaler [see Adverse Reactions (6.1)]. Bronchospasm should be treated as medically appropriate.
5.5 Laboratory Tests
Audiograms

Physicians should consider an audiogram at baseline, particularly for patients at increased risk of auditory dysfunction.

If a patient reports tinnitus or hearing loss during TOBI Podhaler therapy, the physician should refer that patient for audiological assessment.

Serum Concentrations

In patients treated with TOBI Podhaler, serum tobramycin concentrations are approximately 1 to 2 µg/mL one hour after dose administration and do not require routine monitoring. Serum concentrations of tobramycin in patients with known or suspected auditory or renal dysfunction or patients treated with a concomitant parenteral aminoglycoside (or other nephrotoxic or ototoxic medications) should be monitored at the discretion of the treating physician. If ototoxicity or nephrotoxicity occurs in a patient receiving TOBI Podhaler, tobramycin therapy should be discontinued until serum concentrations fall below 2 µg/mL.

The serum concentration of tobramycin should only be monitored through venipuncture and not finger prick blood sampling. Contamination of the skin of the fingers with tobramycin may lead to falsely increased measurements of serum levels of the drug. This contamination cannot be completely avoided by hand washing before testing.

Renal Function

Laboratory tests of urine and renal function should be conducted at the discretion of the treating physician.
5.6 Use in Pregnancy
Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides cross the placenta, and streptomycin has been associated with several reports of total, irreversible, bilateral congenital deafness in pediatric patie