indication

For the treatment of pseudomonas aeruginosa lung infections. Also being investigated for use in the treatment of sinus infections.

pharmacology

Tobramycin, an aminoglycoside antibiotic obtained from cultures of Streptomyces tenebrarius, is used in combination with other antibiotics to treat urinary tract infections, gynecologic infections, peritonitis, endocarditis, pneumonia, bacteremia and sepsis, respiratory infections including those associated with cystic fibrosis, osteomyelitis, and diabetic foot and other soft-tissue infections. It acts primarily by disrupting protein synthesis, leading to altered cell membrane permeability, progressive disruption of the cell envelope, and eventual cell death. Tobramycin has in vitro activity against a wide range of gram-negative organisms including Pseudomonas aeruginosa.

mechanism of action

Tobramycin binds irreversibly to one of two aminoglycoside binding sites on the 30 S ribosomal subunit, inhibiting bacterial protein synthesis. Tobramycin may also destabilize bacterial memebrane by binding to 16 S 16 S r-RNA. An active transport mechanism for aminoglycoside uptake is necessary in the bacteria in order to attain a significant intracellular concentration of tobramycin.

toxicity

LD₅₀=441mg/kg (s.c. in mice)

absorption

The bioavailability of tobramycin may vary because of individual differences in nebulizer performance and airway pathology.

half life

The elimination half-life of tobramycin from serum is approximately 2 hours after intravenous (IV) administration.

drug interactions

Acetazolamide: Increased risk of nephrotoxicity

Amphotericin B: Increased risk of nephrotoxicity

Atracurium: The agent increases the effect of the muscle relaxant

Benazepril: Increased risk of nephrotoxicity

Bumetanide: Increased ototoxicity

Candesartan: Increased risk of nephrotoxicity

Captopril: Increased risk of nephrotoxicity

Cefamandole: Increased risk of nephrotoxicity

Cefazolin: Increased risk of nephrotoxicity

Cefonicid: Increased risk of nephrotoxicity

Cefoperazone: Increased risk of nephrotoxicity

Ceforanide: Increased risk of nephrotoxicity

Cefotaxime: Increased risk of nephrotoxicity

Cefotetan: Increased risk of nephrotoxicity

Cefoxitin: Increased risk of nephrotoxicity

Cefradine: Increased risk of nephrotoxicity

Ceftazidime: Increased risk of nephrotoxicity

Ceftizoxime: Increased risk of nephrotoxicity

Ceftriaxone: Increased risk of nephrotoxicity

Cefuroxime: Increased risk of nephrotoxicity

Cephalothin Group: Increased risk of nephrotoxicity

Cephapirin: Increased risk of nephrotoxicity

Cisplatin: Increased risk of nephrotoxicity

Colistimethate: Increased risk of nephrotoxicity

Cyclosporine: Increased risk of nephrotoxicity

Didanosine: Increased risk of nephrotoxicity

Doxacurium chloride: The agent increases the effect of the muscle relaxant

Enalapril: Increased risk of nephrotoxicity

Ethacrynic acid: Increased ototoxicity

Fosinopril: Increased risk of nephrotoxicity

Furosemide: Increased ototoxicity

Heparin: Increased risk of nephrotoxicity

Irbesartan: Increased risk of nephrotoxicity

Lamivudine: Increased risk of nephrotoxicity

Lisinopril: Increased risk of nephrotoxicity

Lithium: Increased risk of nephrotoxicity

Losartan: Increased risk of nephrotoxicity

Metocurine: The agent increases the effect of the muscle relaxant

Mivacurium: The agent increases the effect of the muscle relaxant

Olmesartan: Increased risk of nephrotoxicity

Pancuronium: The agent increases the effect of the muscle relaxant

Perindopril: Increased risk of nephrotoxicity

Phenytoin: Increased risk of nephrotoxicity

Pipecuronium: The agent increases the effect of the muscle relaxant

Quinapril: Increased risk of nephrotoxicity

Ramipril: Increased risk of nephrotoxicity

Rocuronium: The agent increases the effect of the muscle relaxant

Spironolactone: Increased risk of nephrotoxicity

Succinylcholine: The agent increases the effect of the muscle relaxant

Sulfamethoxazole: Increased risk of nephrotoxicity

Tacrolimus: Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Tobramycin. Use caution during concomitant therapy.

Telmisartan: Increased risk of nephrotoxicity

Thalidomide: Thalidomide increases the renal toxicity of the aminoglycoside

Ticarcillin: Ticarcillin may reduce the serum concentration of Tobramycin. Ticarcillin may inactivate Tobramycin in vitro and the two agents should not be administered simultaneously through the same IV line.

Topiramate: Increased risk of nephrotoxicity

Torasemide: Increased ototoxicity

Trimethoprim: Increased risk of nephrotoxicity

Tubocurarine: The agent increases the effect of the muscle relaxant

Valsartan: Increased risk of nephrotoxicity

Vancomycin: Increased risk of nephrotoxicity

Vecuronium: The agent increases the effect of the muscle relaxant