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. |
| Molecular Weight | 477.6 |
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 | Avoid; associated with fetal ototoxicity and nephrotoxicity risk; use only for life-threatening infections. |
| 2nd trimester | Avoid; use only if clearly needed; risk of fetal nephrotoxicity and ototoxicity. |
| 3rd trimester | Avoid; increased risk of fetal nephrotoxicity and ototoxicity; may cause neonatal hypocalcemia. |
Clinical note
Comprehensive clinical and safety monograph for GENTAFAIR (GENTAFAIR).
| Placental transfer | Crosses placenta; achieves fetal serum concentrations 30-60% of maternal levels. |
| Breastfeeding | Gentamicin is excreted into breast milk in low concentrations. However, due to the potential for infant gut flora alteration and rare reports of nephrotoxicity, consider the benefits of breastfeeding against the risk of exposure. Monitor infant for diarrhea, blood in stools, or fungal infections. |
■ 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 or any aminoglycosideMyasthenia gravis (risk of neuromuscular blockade)Preexisting severe renal impairment (unless benefit outweighs risk and dosing adjusted)Concurrent use of other nephrotoxic or ototoxic drugs (e.g., cisplatin, amphotericin B, loop diuretics) unless absolutely necessary
| 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 |
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| Lactation Rating | L2 (Probably Compatible) |
| 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. |
| 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. |
| Food/Dietary | No significant food interactions; however, maintain adequate hydration to reduce nephrotoxicity risk. Avoid alcohol during treatment due to potential for increased side effects (e.g., dizziness, nausea). No specific dietary restrictions required. |
| Clinical Pearls | Gentamicin is an aminoglycoside antibiotic with concentration-dependent killing and post-antibiotic effect. Therapeutic drug monitoring (TDM) is essential; target peak 5-10 mcg/mL (once-daily dosing) or trough <1-2 mcg/mL (traditional dosing). Adjust dose or interval based on renal function. Ototoxicity (vestibular > cochlear) and nephrotoxicity are dose-limiting; monitor audiometry and serum creatinine. Avoid concurrent use of other nephrotoxic drugs (e.g., NSAIDs, vancomycin, loop diuretics) and neuromuscular blocking agents. For once-daily dosing, extend interval in renal impairment using Hartford nomogram; goal peak concentration >10-20 mcg/mL with trough <1 mcg/mL. Intrathecal or intraventricular administration may be used for CNS infections; ensure preservative-free formulation. Synergy with beta-lactams against enterococci and Pseudomonas. |
| Patient Advice | Take this medication exactly as prescribed, usually once or twice daily by intravenous or intramuscular injection; do not skip doses. · You may experience dizziness, ringing in the ears, hearing loss, or balance problems; report these symptoms immediately. · Drink plenty of fluids unless told otherwise by your doctor to help prevent kidney problems. · Tell your doctor if you have kidney disease, hearing loss, or myasthenia gravis before starting therapy. · Notify all healthcare providers that you are receiving gentamicin; it may interact with other medications such as diuretics and muscle relaxants. · Complete the full course of therapy even if you feel better. |