Netilmicin is a semisynthetic aminoglycoside antibiotic, and a derivative of sisomicin, produced by Micromonospora inyoensis. Aminoglycoside antibiotics have the ability to kill a wide variety of bacteria. Netilmicin is not absorbed from the gut and is therefore administered parenterally, most commonly by intramuscular or intravenous injection; it is supplied as the sulfate salt for clinical use. Mechanism of action is concentration dependent bactericidal activity via reversible binding to the 30S ribosomal subunit with disruption of initiation complex formation and increased miscoding during protein synthesis. Pharmacokinetics are characterized by limited tissue distribution to the extracellular fluid compartment, low plasma protein binding, predominant renal excretion by glomerular filtration and a plasma half-life that prolongs in renal impairment, requiring dose adjustment. Netilmicin demonstrates potent activity against many aerobic Gram negative bacilli including Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp and retains activity against some gentamicin resistant strains due to reduced susceptibility to certain aminoglycoside-modifying enzymes. Clinical use requires therapeutic drug monitoring of peak and trough concentrations, and monitoring of renal function and auditory/vestibular status because of nephrotoxicity and ototoxicity risks.
Parent: Gentamicin Sulfate/ Netilmicin Sulfate
Parent: Netilmicin
Parent: Netilmicin
Parent: Netilmicin
Active substance specifications typically require an assay of netilmicin expressed as netilmicin base in the range of approximately 95.0 to 105.0 percent. Related substances and impurities are controlled by validated chromatographic methods such as HPLC or LC-MS; typical acceptance criteria used in pharmaceutical specifications are each unspecified impurity not greater than 0.5 percent and total impurities not greater than 2.0 percent. Known related compounds that are monitored include sisomicin and minor netilmicin congeners and degradation products derived from the core aminoglycoside structure; individual related compounds of known identity are commonly limited to 0.5 to 1.0 percent depending on the impurity qualification status. Additional quality limits address heavy metals (for example not more than 20 parts per million), residual solvents and microbiological/endotoxin limits per pharmacopeial guidance. These limits and analytical procedures should follow the applicable pharmacopeia and ICH quality guidelines for impurities and stability.
Netilmicin is used to treat serious infections caused by susceptible aerobic Gram negative bacteria and certain Gram positive organisms, for example severe sepsis, complicated intra-abdominal infections, nosocomial lower respiratory infections, complicated urinary tract infections and infections with multidrug resistant organisms when appropriate; it is reserved for situations requiring a parenteral aminoglycoside and where local susceptibility data support its use.
Chemically netilmicin is a 1-N-ethyl derivative of sisomicin which confers lower susceptibility to many aminoglycoside-modifying enzymes; as a result netilmicin can retain activity against some isolates that are resistant to gentamicin. Clinically both drugs share a similar mechanism of action and similar toxicity profiles including nephrotoxicity and ototoxicity, but netilmicin may offer an advantage in specific resistant infections based on susceptibility testing.
Netilmicin is given parenterally by intramuscular or intravenous injection according to weight-based dosing and renal function. Typical adult dosing ranges from about 4 to 6 mg per kg per day given either as once-daily dosing (for example around 6 mg/kg once daily where supported by local protocols) or as divided doses, with precise regimens and infusion rates adjusted by indication, patient age and renal clearance. Dose adjustment and interval extension are required in renal impairment and therapeutic drug monitoring of peak and trough concentrations is recommended to optimize efficacy and minimize toxicity.
Netilmicin targets many aerobic Gram negative bacilli including Escherichia coli, Klebsiella spp, Enterobacter spp, Pseudomonas aeruginosa and Acinetobacter spp, and has activity against some Gram positive pathogens such as Staphylococcus aureus. It has minimal or no activity against most anaerobic bacteria and its use should be guided by culture and susceptibility results.
