TOBRAMYCIN
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Aminoglycoside antibiotic that irreversibly binds to the 30S ribosomal subunit, inhibiting protein synthesis and causing bacterial cell death. Exhibits concentration-dependent bactericidal activity.
| Metabolism | Primarily eliminated unchanged by glomerular filtration. Minimal hepatic metabolism. |
| Excretion | Renal excretion of unchanged drug via glomerular filtration: >90% within 24 hours. Minimal biliary/fecal elimination (<5%). |
| Half-life | 2–3 hours (normal renal function); prolonged to 24–60 hours in anuria. Clinical context: dosing interval must be adjusted for renal impairment to avoid accumulation and toxicity. |
| Protein binding | <30% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.2–0.3 L/kg (low, predominantly extracellular fluid). Clinical meaning: poor intracellular penetration; distributes mainly into interstitial space. |
| Bioavailability | IM: ~90%; Nebulized: 5–15% systemic bioavailability due to limited pulmonary absorption. |
| Onset of Action | IV: immediate; IM: 30–60 minutes; Nebulized: variable, within 15–30 minutes. |
| Duration of Action | IV/IM: 6–8 hours (dose-dependent); Nebulized: 12 hours antimicrobial effect in airway secretions. |
5-7 mg/kg IV once daily; 2-4 mg/kg/day IV divided every 8 hours for synergy; 2-4 mg/kg IM divided every 8 hours; 3-5 mg/kg/day IV for cystic fibrosis. Inhalation: 300 mg every 12 hours (nebulizer). Intrathecal: 5-20 mg/day.
| Dosage form | SOLUTION |
| Renal impairment | CrCl >50 mL/min: 5-7 mg/kg q24h; CrCl 30-50: 5-7 mg/kg q24-36h; CrCl 20-29: 5-7 mg/kg q48h; CrCl 10-19: 5-7 mg/kg q48-72h; CrCl <10: 5-7 mg/kg q72-96h (with monitoring). |
| Liver impairment | No specific Child-Pugh based modifications; use with caution in severe hepatic impairment due to potential nephrotoxicity; monitor serum levels. |
| Pediatric use | Neonates ≤7 days: 4 mg/kg IV q24h; Neonates 8-28 days: 4 mg/kg IV q18h; Infants/Children: 2.5 mg/kg IV q8h or 5-7 mg/kg IV q24h; Inhalation: 300 mg q12h (≥6 years). |
| Geriatric use | Start at lower end of dosing range (e.g., 5 mg/kg IV q24h) due to age-related renal decline; adjust dose based on CrCl; monitor serum creatinine and drug levels. |
| 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.
| Breastfeeding | Enters breast milk; M/P ratio not established. Low oral bioavailability in infants minimizes systemic exposure, but potential for gut flora alteration and ototoxicity. Use with caution; monitor infant for diarrhea, hearing loss, or renal dysfunction. |
| Teratogenic Risk | FDA Pregnancy Category D. Animal studies (rats, rabbits) at doses up to 2-3 times human dose showed no teratogenicity but caused fetal nephrotoxicity and ototoxicity. Human data insufficient; potential for fetal harm (e.g., ototoxicity, nephrotoxicity). Avoid in pregnancy unless benefit outweighs risk. First trimester: avoid; second/third trimester: use only for serious infections with caution. |
■ FDA Black Box Warning
Aminoglycosides can cause nephrotoxicity and ototoxicity (both vestibular and auditory) which may be irreversible. Neurotoxicity (including neuromuscular blockade) may also occur. Risk is greater in patients with renal impairment, pre-existing hearing loss, concomitant use of other nephrotoxic or ototoxic drugs, and prolonged use. Monitor renal function and eighth cranial nerve function during therapy.
| Common Effects | Nephrotoxicity |
| Serious Effects |
["Hypersensitivity to tobramycin or any aminoglycoside","Pre-existing severe hearing loss (relative contraindication)"]
| Precautions | ["Nephrotoxicity: Monitor renal function (serum creatinine, BUN) and adjust dosing accordingly.","Ototoxicity: Monitor for hearing loss, tinnitus, or vertigo; audiologic tests recommended.","Neuromuscular blockade: Use caution in patients with neuromuscular disorders (e.g., myasthenia gravis, Parkinson's) or receiving neuromuscular blocking agents.","Hypersensitivity reactions: Cross-allergenicity among aminoglycosides.","Superinfection: Prolonged use may result in overgrowth of nonsusceptible organisms.","Use in pregnancy: Aminoglycosides cross the placenta and may cause fetal harm.","Pediatric use: Risk of ototoxicity in neonates and young children.","Geriatric use: Increased risk of nephrotoxicity and ototoxicity due to age-related renal decline."] |
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| Fetal Monitoring | Monitor maternal serum trough (target <1-2 mcg/mL) and peak (target 5-10 mcg/mL). Assess renal function (serum creatinine, BUN, urinalysis). Perform audiometry before and during therapy. Fetal: ultrasound for growth and amniotic fluid volume (risk of oligohydramnios). |
| Fertility Effects | No direct evidence of human fertility impairment. Animal studies show no adverse effects on fertility at therapeutic doses. However, aminoglycosides may rarely cause transient maternal renal impairment, indirectly affecting reproductive function. |