Netilmicin

Pharmaceuticals -> Antibiotics

Pharmaceuticals -> Antibiotics

Pharmaceuticals -> Listed in ZINC15

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Concurrent and/or sequential use of 2 or more aminoglycosides by any route or concurrent use of capreomycin with aminoglycosides should be avoided since the potential for ototoxicity, nephrotoxicity, and neuromuscular blockade may be increased; hearing loss may occur and may progress to deafness even after discontinuation of the drug; loss of hearing may be reversible, but usually is permanent; neuromuscular blockade may result in skeletal muscle weakness and respiratory depression or paralysis (apnea). Also, concurrent use of 2 or more aminoglycosides may result in reduced bacterial uptake of each one since the medications compete for the same uptake mechanism. /Aminoglycosides/

Concurrent use of medications with neuromuscular blocking activity, including halogenated hydrocarbon inhalation anesthetics, opioid analgesics, and massive transfusions with citrate anticoagulated blood, with aminoglycosides should be carefully monitored since neuromuscular blockade may be enhanced, resulting in skeletal muscle weakness and respiratory depression or paralysis (apnea); caution is recommended when these medications and aminoglycosides are used concurrently during surgery or in the postoperative period, especially if there is a possibility of incomplete reversal of neuromuscular blockade postoperatively; treatment with anticholinesterase agents or calcium salts may help reverse the blockade. /Aminoglycosides/

Vancomycin and aminoglycosides must often be administered concurrently in the prophylaxis of bacterial endocarditis, in the treatment of endocarditis caused by streptococci and Corynebacteria species, in the treatment of resistant staphylococcal infections, or in penicillin-allergic patients; appropriate monitoring will help to reduce the risk of nephrotoxicity or ototoxicity; renal function determinations, serum aminoglycoside and vancomycin concentrations, dosage reductions, and/or dosage interval adjustments, or alternate antibacterials, may be required. /Aminoglycosides/

Concurrent or sequential use of these medications /nephrotoxic or ototoxic medications/ with aminoglycosides may increase the potential for ototoxicity or nephrotoxicity; hearing loss may occur and may progress to deafness even after discontinuation of the drug and may be reversible, but usually is permanent; serial audiometric function determinations may be required with concurrent or sequential use of other ototoxic antibacterials; renal function determinations may be required. /Aminoglycosides/

For more Interactions (Complete) data for NETILMICIN (9 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

Netilmicin

DILI Positive

DOI:10.1016/j.drudis.2019.09.022

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

S - Sensory organs

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

QS - Sensory organs

Netilmicin is a semisynthetic, water soluble antibiotic of the aminoglycoside group, produced by the fermentation of Micromonospora inyoensis, a species of actinomycete. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. It is active at low concentrations against a wide variety of pathogenic bacteria including <i>Escherichia coli</i>, bacteria of the <i>Klebsiella-Enterobacter-Serratia </i>group, <i>Citrobacter </i>sp., <i>Proteus </i>sp. (indole-positive and indole-negative), including <i>Proteus mirabilis</i>, <i>P. morganii, P. rettgrei, P. vulgaris, Pseudomonas aeruginosa </i>and <i>Neisseria gonorrhoea</i>. Netilmicin is also active <i>in vitro </i>against isolates of <i>Hemophilus influenzae, Salmonella </i>sp., <i>Shigella </i>sp. and against penicillinase and non-penicillinase-producing <i>Staphylococcus </i>including methicillin-resistant strains. Some strains of <i>Providencia </i>sp., <i>Acinetobacter </i>sp. and <i>Aeromonas </i>sp. are also sensitive to netilmicin. Many strains of the above organisms which are found to be resistant to other aminoglycosides, such as kanamycin, gentamicin, tobramycin and sisomicin, are susceptible to netilmicin <i>in vitro</i>. Occasionally, strains have been identified which are resistant to amikacin but susceptible to netilmicin. The combination of netilmicin and penicillin G has a synergistic bactericidal effect against most strains of <i>Streptococcus faecalis</i> (enterococcus). The combined effect of netilmicin and carbenicillin or ticarcillin is synergistic for many strains of <i>Pseudomonas aeruginosa</i>. In addition, many isolates of <i>Serratia</i>, which are resistant to multiple antibiotics, are inhibited by synergistic combinations of netilmicin with carbenicillin, azlocillin, mezlocillin, cefamandole, cefotaxime or moxalactam. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.

Aminoglycosides like netilmicin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically netilmicin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes, leaving the bacterium unable to synthesize proteins vital to its growth.

Aminoglycosides are usually bacterial in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. /Aminoglycosides/

/AMINOGLYCOSIDES/ INHIBIT PROTEIN BIOSYNTHESIS & DECR FIDELITY OF TRANSLATION OF GENETIC CODE. /AMINOGLYCOSIDES/

2.5 hours

The plasma elimination half-life on netilmicin is about 2-2.5 hr following IV or IM administration of a single dose in adults with normal renal function. The serum half-life is reported to be 18 hr in adults with creatinine clearances of 10-30 mL/min and more than 30 hr in anephric adults. The plasma elimination half-life of netilmicin in neonates is inversely related to birthweight and gestational and postnatal age and has been reported to be about 8 or 4.5 hr in neonates less than 7 days of age weighing 1.5-2 or 3-4 kg, respectively. The plasma elimination half-life for children 6 weeks of age and older is 1.5-2 hr.

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NETILMICIN

Established Pharmacologic Class [EPC] - Aminoglycoside Antibacterial

Chemical Structure [CS] - Aminoglycosides

Netilmicin is an Aminoglycoside Antibacterial.

Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.

Substances that inhibit the growth or reproduction of BACTERIA.

Rapidly and completely absorbed after IM administration, peak serum levels were achieved within 30-60 minutes. Aminoglycosides are poorly absorbed orally. Topical absorption is also poor unless severe skin damage is present.

Netilmicin is poorly absorbed from the intact GI tract following oral administration. The drug is rapidly and completely absorbed following IM administration.

Following absorption, netilmicin rapidly distributes into tissues, sputum, and pericardial, synovial, and peritoneal fluids. ...distributed principally in the extracellular fluid volume... The volume of distribution ...is approximately 20% of body weight. The drug is reportedly 0-30% protein bound.

Netilmicin crosses the placenta and has been detected in cord blood. Small amounts of the drug are distributed into milk.

...is not metabolized and is excreted unchanged in urine mainly by glomerular filtration. In adults with normal renal function, 74% of a 2 mg/kg dose of netilmicin is excreted unchanged within 24 horus: in adults with creatinine clearances of 30-80 or 10-30 mL/min or in anephric adults, 55, 25, or 15% of the dose is excreted in urine within 24 hours, respectively.

Netilmicin is removed by hemodialysis. The drug is also removed by peritoneal dialysis but less readily than by hemodialysis.