TOBRAMYCIN

What it is

Tobramycin is supplied as a single-use 5 mL ampoule containing 300 mg tobramycin and 11.25 mg sodium chloride in sterile water for injections. The formulation is specifically developed for administration by inhalation. It is a clear, colourless to light yellow solution, free from visible particulates. Tobramycin is an aminoglycoside antibiotic produced by Streptomyces tenebrarius.

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. Tobramycin is administered twice daily in alternating periods of 28 days. After 28 days of therapy, patients should stop therapy for the next 28 days, and then resume therapy for the next 28 day on/28 day off cycle. The doses should be taken as close to 12 hours apart as possible; they should not be taken less than six hours apart. The medicine is administered by inhalation, over an approximately 15 minute period, using a hand-held nebuliser and compressor.

Key safety warnings

In clinical studies, 4 patients (1%) reported mild to moderate hearing loss in clinical studies of up to 9 treatment cycles of tobramycin solution. Hearing loss was transient for 3 patients and ongoing at the end of study for one patient. Three of these patients had received IV aminoglycosides concomitantly to receiving tobramycin solution. 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. Ototoxicity occurred in some patients even when their aminoglycoside serum levels were within the recommended range. In case of known maternal history of ototoxicity due to aminoglycoside use or a known mitochondrial DNA variant in the patient, consider alternative treatments other than aminoglycosides unless the increased risk of permanent hearing loss is outweighed by the severity of infection and lack of safe and effective alternative therapies. Nephrotoxicity was not seen during tobramycin solution clinical studies but has been associated with aminoglycosides as a class. Laboratory tests of renal function should be monitored as clinically appropriate. Urea and creatinine levels should be reassessed after every 6 complete cycles of therapy. Tobramycin solution should be used cautiously in patients with muscular 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. Bronchospasm can occur with inhalation of medicinal products and has been reported with tobramycin solution. 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.

Contraindications

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

PBS listing

Injection 80 mg in 2 mL is listed on the PBS with restriction, with an ex-manufacturer price of A$12.30.

Regulatory history

Tobramycin SUN was first approved on 15 December 2017.