⛔ FDA Black Box Warning
WARNING: NEPHROTOXICITY, OTOTOXICITY AND EMBRYO-FETAL TOXICITY WARNING: NEPHROTOXICITY, OTOTOXICITY, NEURO MUSCULAR BLOCKADE AND FETAL HARM See full prescribing information for complete boxed warning. Nephrotoxicity Tobramycin for Injection may cause acute kidney injury. Monitor renal function and serum tobramycin concentrations in all patients. Reduce the dose or discontinue the Tobramycin for Injection if renal impairment occurs. ( 5.1 ) Ototoxicity Tobramycin for Injection may cause irreversible auditory and vestibular toxicity. Monitor for symptoms of ototoxicity, and for renal function and serum tobramycin levels in all patients. Reduce the dose or discontinue the Tobramycin for Injection if impairment of renal function occurs. Discontinue Tobramycin for Injection if ototoxicity occurs. ( 5.2 ) Neuromuscular Blockade Aminoglycosides have been associated with neuromuscular blockade. During therapy with Tobramycin for Injection, monitor for adverse reactions associated with neuromuscular blockade, particularly in high-risk patients ( 5.5 ) Embryo-Fetal Toxicity Tobramycin for Injection and other aminoglycosides can cause fetal harm when administered to a pregnant woman. Apprise pregnant women of the potential hazard to the fetus. ( 5.3 , 8.1 ) Nephrotoxicity Tobramycin for Injection can result in acute kidney injury, including acute renal failure. Risk factors that may contribute to nephrotoxicity include tobramycin accumulation (increasing serum trough levels), high peak concentrations (above 12 mcg/mL), total cumulative dose, advanced age, volume depletion and concurrent or sequential use of other nephrotoxic drugs. Avoid concurrent or sequential use of other potentially nephrotoxic drugs. Monitor serum tobramycin levels and renal function in all patients during drug treatment. Reduce the dose or discontinue the Tobramycin for Injection if renal impairment occurs [see Warnings and Precautions ( 5.1 )]. Ototoxicity Tobramycin for Injection can cause irreversible
Contraindications
4 CONTRAINDICATIONS Tobramycin for Injection is contraindicated in patients with a history of hypersensitivity to tobramycin or any other aminoglycoside [see Warnings and Precautions ( 5.4 )] . A history of hypersensitivity or serious toxic reactions to any aminoglycoside ( 4 ).
Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary Aminoglycosides, including Tobramycin for Injection, can cause fetal harm when administered to a pregnant woman. Published literature reports that use of streptomycin, an aminoglycoside, can cause total, irreversible, bilateral congenital deafness when administered to a pregnant woman [see Warnings and Precautions ( 5.3 )]. In animal reproduction studies with subcutaneous administration of tobramycin in pregnant rats and rabbits during organogenesis, there were no adverse developmental outcomes at doses up to 3.2 times and 1.3 times the maximum recommended clinical dose based on body surface area; however, ototoxicity was not evaluated in the offspring from these studies (see Data ). Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20% respectively. Data Animal Data Subcutaneous administration of tobramycin at doses of up to 100 mg/kg/day (rat) or 20 mg/kg/day (rabbit) during organogenesis was not associated with adverse developmental outcomes. These doses are 3.2 and 1.3 times the maximum recommended clinical daily dose of 5 mg/kg based on body surface area. Doses of tobramycin ≥40 mg/kg/day were maternally toxic to rabbits and precluded the evaluation of adverse developmental outcomes. Ototoxicity was not evaluated in offspring during nonclinical reproductive toxicity studies with tobramycin.