TOBI

What it is

TOBI is a tobramycin solution for inhalation, supplied as a single-use 5 mL ampoule containing 300 mg tobramycin. The formulation is specifically developed for administration by inhalation. Tobramycin is an aminoglycoside antibiotic that acts primarily by disrupting protein synthesis, leading to altered cell membrane permeability, progressive disruption of the cell envelope, and eventual cell death.

Approved indications

— Management of cystic fibrosis patients with Pseudomonas aeruginosa infections.

Dosing overview

The recommended dosage for both adults and paediatric patients 6 years of age and older is one single-use ampoule (300 mg) administered twice daily for 28 days. TOBI is administered twice daily in alternating periods of 28 days on therapy followed by 28 days off therapy. Doses should be taken as close to 12 hours apart as possible and should not be taken less than six hours apart. The solution is administered by inhalation over approximately 15 minutes using a hand-held nebuliser and compressor.

Key safety warnings

In clinical studies, 4 patients (1%) reported mild to moderate hearing loss, with hearing loss being transient for 3 patients and ongoing at the end of study for one patient. Cases of ototoxicity with aminoglycosides have been observed in patients with certain variants in the mitochondrially encoded 12S rRNA gene (MT-RNR1), particularly the m.1555A>G variant, and ototoxicity occurred in some patients even when their aminoglycoside serum levels were within the recommended range. Physicians should consider an audiogram before initiating tobramycin therapy for patients who show any evidence of auditory dysfunction, or who are at increased risk for auditory dysfunction, and if a patient reports tinnitus or hearing loss during therapy, the physician should refer them for audiological assessment. Bronchospasm can occur with inhalation of medicinal products and has been reported with tobramycin solution, and should be treated as medically appropriate. Cough was the most commonly reported adverse event considered treatment related for tobramycin solution, and if there is evidence of continued therapy-induced cough, the physician should consider the use of alternative therapeutic options. Aminoglycosides can cause foetal 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 paediatric patients exposed in utero, and patients who use tobramycin during pregnancy, or become pregnant while taking this product should be apprised of the potential hazard to the foetus.

Contraindications

Tobramycin is contraindicated in patients with a known hypersensitivity to any aminoglycoside.

PBS listing

The solution for inhalation 300 mg in 5 mL is listed on the PBS with streamlined restriction and an ex-manufacturer price of A$322.41.

Regulatory history

TOBI solution for inhalation was first listed on the ARTG on 18 February 2000. TOBI Podhaler (tobramycin 28 mg hard capsule for inhalation) was first listed on the ARTG on 6 March 2012. The TGA approved TOBI Podhaler, a new dry powder inhalation formulation of tobramycin, for the management of Pseudomonas aeruginosa infections in cystic fibrosis patients, with this approval granted for the same indication as the existing nebulised tobramycin solution, with the new formulation aiming to improve patient compliance through reduced administration time and increased portability. In July 2017, the PBAC noted no further action was recommended after noting the report regarding the use of inhaled tobramycin for Pseudomonas aeruginosa infection in cystic fibrosis.