TOBRAMYCIN SULFATE (PHARMACY BULK)
Clinical safety rating: avoid
Other nephrotoxic or ototoxic drugs increase risk of toxicity Monitor peak and trough levels to minimize risk of nephrotoxicity and ototoxicity.
Aminoglycoside antibiotic that binds to the 30S ribosomal subunit, causing misreading of mRNA and inhibiting protein synthesis, leading to bacterial cell death. Bactericidal against Gram-negative aerobes.
| Metabolism | Primarily excreted unchanged by the kidneys via glomerular filtration. Minimal hepatic metabolism. |
| Excretion | Primarily renal excretion of unchanged drug via glomerular filtration; >90% of dose recovered in urine within 24 hours. Biliary/fecal elimination is minimal (<1%). |
| Half-life | Terminal elimination half-life of 2–3 hours in patients with normal renal function; prolonged to 24–60 hours in anuria/end-stage renal disease. In neonates, half-life may be 4–12 hours depending on gestational age. |
| Protein binding | 30–40% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is 0.25–0.40 L/kg, approximating extracellular fluid volume. Increased Vd in edematous states (e.g., ascites, burns) and decreased in dehydrated patients. |
| Bioavailability | Oral bioavailability <1%; administered parenterally (IM/IV) for systemic effects. Nebulized tobramycin yields negligible systemic absorption (<1% of dose). |
| Onset of Action | Intramuscular or intravenous: Onset of action occurs within 30–60 minutes after administration, with peak serum concentrations achieved by 30 minutes after IV infusion or 60 minutes after IM injection. Nebulized: Onset of action is within 15–30 minutes for local pulmonary effects. |
| Duration of Action | Duration of action is approximately 6–8 hours for systemic administration, limited by rapid renal clearance; serum concentrations should be monitored to maintain therapeutic levels. Nebulized tobramycin provides sustained local effects in the lungs for up to 12 hours after a single dose, but systemic levels are negligible. |
5-7 mg/kg IV q24h (extended-interval) or 1.5-2.5 mg/kg IV q8h (traditional dosing) for serious Gram-negative infections; adjust based on therapeutic drug monitoring.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 10-50 mL/min: prolong interval (e.g., q24-48h). CrCl <10 mL/min: q48-72h or per serum levels. Use lower traditional doses if extended-interval contraindicated. Monitor peak and trough. |
| Liver impairment | No dose adjustment required for hepatic impairment. Pharmacokinetics not significantly altered in Child-Pugh A, B, or C. However, monitor renal function as underlying disease may co-exist. |
| Pediatric use | Neonates: 2.5 mg/kg IV q12h (postnatal age <7 days) or q8h (7-28 days). Infants/children: 2.5 mg/kg IV q8h (traditional) or 5-7 mg/kg IV q24h (extended-interval). Cystic fibrosis: higher doses (7-10 mg/kg IV q24h). Adjust per TDM. |
| Geriatric use | Use lower initial doses based on ideal body weight and renal function. Monitor renal function (eGFR) and serum concentrations closely. Extended-interval dosing may be preferred with careful trough monitoring. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other nephrotoxic or ototoxic drugs increase risk of toxicity Monitor peak and trough levels to minimize risk of nephrotoxicity and ototoxicity.
| FDA category | Positive |
| Breastfeeding | Tobramycin is excreted into breast milk in low concentrations. M/P ratio approximately 0.25-0.46. Oral bioavailability in infants is poor, so systemic effects are unlikely. However, potential for alteration of infant gut microbiota and risk of hypersensitivity. Use with caution, monitor infant for diarrhea, rash, or fungal overgrowth. |
| Teratogenic Risk |
■ FDA Black Box Warning
Aminoglycosides, including tobramycin, are associated with nephrotoxicity and ototoxicity (vestibular and auditory). Risk is higher with renal impairment, prolonged use, high doses, or concurrent ototoxic/nephrotoxic drugs. Neurotoxicity (neuromuscular blockade) may occur, especially with anesthetics or neuromuscular blocking agents. Avoid use in patients with hypersensitivity to aminoglycosides.
| Common Effects | Nephrotoxicity |
| Serious Effects |
ototoxicity
| Precautions | Other nephrotoxic or ototoxic drugs increase risk of toxicity Monitor peak and trough levels to minimize risk of nephrotoxicity and ototoxicity. |
Loading safety data…
| Aminoglycosides cross the placenta. First trimester: No well-documented increased risk of major malformations, but data limited. Second and third trimesters: Potential for fetal ototoxicity (eighth cranial nerve damage) and nephrotoxicity, especially with prolonged or high-dose therapy. Risk of bilateral congenital deafness reported. |
| Fetal Monitoring | Maternal: Renal function (serum creatinine, BUN), urinalysis, audiometry at baseline and periodically, serum drug levels (trough and peak) to avoid toxicity. Fetal: Ultrasound monitoring for fetal growth and amniotic fluid volume if used for prolonged periods; consider newborn hearing screen after delivery if exposure in late pregnancy. |
| Fertility Effects | In animal studies, no impairment of fertility was observed. Human data limited. No known effect on spermatogenesis or oogenesis at therapeutic doses. Systemic toxicity (nephrotoxicity, ototoxicity) may indirectly affect general health and fertility. |