From the Guidelines
Aminoglycosides can result in permanent auditory, vestibular, and renal toxicity, emphasizing the need for careful monitoring during treatment. The risk of adverse events is greatest when aminoglycoside levels exceed recommended levels, but it also varies according to the specific aminoglycoside prescribed, duration of exposure, route of administration, and host susceptibility 1. Key adverse effects include:
- Ototoxicity, which can lead to hearing loss and vestibular problems, with the risk associated with older age, duration of treatment, and cumulative dose 1.
- Vestibular toxicity, usually resolving on its own, found in a smaller proportion of patients compared to ototoxicity 1.
- Renal toxicity, which is typically mild and reversible, occurring in some patients 1. It's crucial to note that mutations in mitochondrial DNA may increase the risk of aminoglycoside ototoxicity, although current evidence does not support altering prescribing practices based on the presence or absence of these mutations 1. Monitoring for these adverse effects, particularly in patients with risk factors such as pre-existing renal impairment, advanced age, or those on prolonged therapy, is essential to minimize the risks associated with aminoglycoside treatment.
From the FDA Drug Label
Patients treated with aminoglycosides should be under close clinical observation because of the potential toxicity associated with their use. As with other aminoglycosides, gentamicin injection is potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high dosage of prolonged therapy Neurotoxicity manifested by ototoxicity, both vestibular and auditory, can occur in patients treated with gentamicin, primarily in those with pre-existing renal damage and in patients with normal renal function treated with higher doses and/or for longer periods than recommended. Aminoglycoside-induced ototoxicity is usually irreversible Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions.
The adverse effects of aminoglycosides, such as gentamicin, include:
- Nephrotoxicity: potentially causing kidney damage, especially in patients with impaired renal function or those receiving high doses or prolonged therapy
- Neurotoxicity: manifested by ototoxicity (vestibular and auditory), which is usually irreversible, as well as other symptoms like numbness, skin tingling, muscle twitching, and convulsions 2
From the Research
Aminoglucosid Adverse Effects
- Aminoglycosides are known to cause nephrotoxicity and ototoxicity, which can lead to renal and vestibular failure 3, 4.
- The mechanism of aminoglycoside-induced nephrotoxicity involves the accumulation of the drug in the kidney, which can be related to the dosing schedule 4.
- Strategies to prevent nephrotoxicity include administering larger doses on a less frequent basis, co-administering protective agents such as polyaspartic acid or defferoxamine, and using population pharmacokinetic computer programs to control serum concentrations 4.
- Single-dose administration of gentamicin has been shown to minimize nephrotoxicity and ototoxicity compared to multiple-dose administration 5, 6.
- The results of a systematic review of randomized trials suggest that once-daily dosing (ODD) regimens of aminoglycosides are safer than multiple daily dosing (MDD) regimens concerning nephrotoxicity, with no significant differences between the two regimens regarding ototoxicity 6.
- Aminoglycoside-induced nephrotoxicity is concerning due to its effects on renal function, but changes are typically reversible 7.
- The mechanism of ototoxicity involves the drug's ability to freely pass into hair cells and cause reactive oxygen species to damage the mitochondria, resulting in cell death 7.
- Exposure to aminoglycosides in utero can result in permanent ototoxicity 7.