GENTAFAIR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GENTAFAIR (GENTAFAIR).
Gentamicin is an aminoglycoside antibiotic that binds to the 30S ribosomal subunit of susceptible bacteria, inhibiting protein synthesis and causing misreading of mRNA, leading to cell death.
| Metabolism | Gentamicin undergoes minimal hepatic metabolism; it is primarily eliminated unchanged by glomerular filtration. |
| Excretion | Renal: over 90% unchanged via glomerular filtration; minor biliary (<1%). |
| Half-life | 2-3 hours (normal renal function); may extend to 24-48 hours in severe renal impairment, necessitating dose adjustment. |
| Protein binding | 0-30% (low), primarily to albumin. |
| Volume of Distribution | 0.2-0.3 L/kg, approximating extracellular fluid volume; indicates limited tissue distribution primarily to extracellular fluid. |
| Bioavailability | IM: ~100% (rapid and complete); oral: negligible (<1%); topical: minimal systemic absorption. |
| Onset of Action | IV: immediate; IM: 30-60 minutes; topical (ophthalmic/otic): within hours, limited systemic absorption. |
| Duration of Action | 8-12 hours following IV/IM; prolonged in renal impairment; drug accumulation increases toxicity risk. |
Gentamicin 3-5 mg/kg IV or IM once daily for serious infections; alternatively, 1.5-2 mg/kg IV or IM every 8 hours.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 20-50 mL/min: extend interval to every 12 hours; CrCl 10-19 mL/min: every 24 hours; CrCl <10 mL/min: 1.5-2 mg/kg loading dose then monitor levels. |
| Liver impairment | No adjustment required for Child-Pugh A or B; for Child-Pugh C, monitor serum levels due to altered volume of distribution. |
| Pediatric use | Neonates: 4-5 mg/kg IV/IM every 24 hours; Infants and children: 2.5 mg/kg IV/IM every 8 hours or 5-7.5 mg/kg once daily. |
| Geriatric use | Initiate with 1.5-2 mg/kg IV/IM based on ideal body weight; monitor renal function and serum levels; use extended dosing interval (e.g., every 24-36 hours) if CrCl <60 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GENTAFAIR (GENTAFAIR).
| Breastfeeding | Gentamicin is excreted into breast milk in small amounts. The M/P ratio is approximately 0.15-0.5. Oral bioavailability in infants is poor, so systemic effects are unlikely. However, monitor infant for diarrhea, candidiasis, or changes in gut flora. Consider risk versus benefit. |
| Teratogenic Risk | Aminoglycosides cross the placenta. There is a potential risk of fetal ototoxicity and nephrotoxicity, particularly if maternal toxicity occurs. Use in pregnancy is generally avoided unless no safer alternative is available. First trimester: limited data, theoretical risk. Second and third trimesters: associated with eighth cranial nerve damage; avoid unless life-threatening infection. |
■ FDA Black Box Warning
Aminoglycosides like gentamicin can cause nephrotoxicity and ototoxicity. The risk of nephrotoxicity is greater in patients with impaired renal function and those who receive high doses or prolonged therapy. Ototoxicity is usually bilateral and irreversible, manifesting as auditory or vestibular damage. Neuromuscular blockade and respiratory paralysis have been reported, especially in patients receiving anesthetics, neuromuscular blocking agents, or massive transfusions. Aminoglycosides should be used in pregnancy only if clearly needed due to potential fetal harm.
| Serious Effects |
["Hypersensitivity to gentamicin, any component of the formulation, or other aminoglycosides","Preexisting auditory or vestibular impairment (relative caution)"]
| Precautions | ["Nephrotoxicity: Monitor renal function (serum creatinine, BUN) before and during therapy","Ototoxicity: Monitor for tinnitus, vertigo, hearing loss; risk increased with high doses, prolonged use, renal impairment, or concurrent loop diuretics","Neuromuscular blockade: Use caution in patients with neuromuscular disorders (e.g., myasthenia gravis, Parkinsonism)","Superinfection: Prolonged use may result in overgrowth of nonsusceptible organisms, including fungi","Hypersensitivity: Serious allergic reactions (e.g., anaphylaxis, exfoliative dermatitis) reported; discontinue if rash or other allergy signs occur"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal renal function (serum creatinine, BUN, urinalysis), serum gentamicin trough and peak levels, and audiometry. In the fetus, consider ultrasound for any signs of ototoxicity (unusual) and monitor amniotic fluid indices if prolonged use. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies have not shown reproductive toxicity at clinically relevant doses. |