Plazomicin

592.68282

592.68

LYO9XZ250J

J - Antiinfectives for systemic use

269

-6.2

1.40±0.1 g/cm3(Predicted)

896.4±65.0 °C(Predicted)

In case of suspected overdose, plazomicin therapy should be discontinued with initiation of supportive care. Maintenance of glomerular filtration and careful monitoring of renal function is recommended. Hemodialysis may be used to facilitate drug elimination, and this may be especially clinically useful in patients with compromised renal function.

Intravenous therapy with plazomicin has been linked to only rare instances of serum enzyme elevations (

The extent of plasma protein binding in humans is approximately 20%. The degree of protein binding was concentration-independent across the range tested in vitro (5 to 100 mcg/mL).

Plazomicin is indicated for the treatment of patients 18 years of age or older with Complicated Urinary Tract Infections (cUTI) including Pyelonephritis, who have limited or no alternative treatment options. It should only be used to treat infections that are proven or strongly suspected to be caused by susceptible microorganisms.|FDA Label

Plazomicin is a parenterally administered, broad spectrum aminoglycoside antibiotic typically used for moderate-to-severe urinary tract infections or pyelonephritis. Plazomicin has had limited clinical use but has not been linked to serum enzyme elevations during therapy or to instances of clinically apparent liver injury.

Aminoglycosides

Plazomicin exerts its antibacterial activity in a dose-dependent manner with a post-antibiotic effect ranging from 0.2 to 2.6 hours at 2X MIC against _Enterobacteriaceae_, as demonstrated by _in vitro_ studies. In clinical trials comprising of hospitalized adult patients with cUTI (including pyelonephritis), resolution or improvement of clinical cUTI symptoms and a microbiological outcome of eradication were observed at day 5 following the first dose administration of plazomicin. Plazomicin has shown to elicit nephrotoxic, ototoxic, and neuromuscular blocking effects. In clinical trials, it did not induce any clinically relevant QTc-prolonging effects.

Administration of 15 mg/kg plazomicin by 30-minute IV infusion resulted in peak plasma concentrations of 73.7 ± 19.7 μg/mL in healthy adult subjects and 51.0 ± 26.7 μg/mL in patients with complicated urinary tract infections (cUTI). The area under the curve (AUC) were 257 ± 67.0 μg.h/mL in healthy adults and 226 ± 113 μg.h/mL in cUTI patients.|Plazomicin predominantly undergoes renal excretion, where 56% of the total administered drug was recovered in the urine within 4 hours following a single 15 mg/kg IV dose of radiolabeled plazomicin in healthy subjects. About less than 0.2% and 89.1% of the total drug were recovered within 168 hours in feces and urine, respectively.|The mean (±SD) volume of distribution is 17.9 (±4.8) L in healthy adults and 30.8 (±12.1) L in cUTI patients.|Following administration of 15 mg/kg plazomicin by 30-minute IV infusion, the mean (±SD) total body clearance in healthy adults and cUTI patients is 4.5 (±0.9) and 5.1 (±2.01) L/h, respectively.

Plazomicin is not reported to undergo significant metabolism.

The mean (±SD) half-life of plazomicin was 3.5 h (±0.5) in healthy adults with normal renal function receiving 15 mg/kg plazomicin via intravenous infusion.

Plazomicin exerts a bactericidal action against susceptible bacteria by binding to bacterial 30S ribosomal subunit. Aminoglycosides typically bind to the ribosomal aminoacyl-tRNA site (A-site) and induce a conformational change to further facilitate the binding between the rRNA and the antibiotic. This leads to codon misreading and mistranslation of mRNA during bacterial protein synthesis. Plazomicin demonstrates potency against _Enterobacteriaceae_, including species with multidrug-resistant phenotypes such as carbapenemase-producing bacteria and isolates with resistance to all other aminoglycosides. Its antibacterial activity is not inhibited by aminoglycoside modifying enzymes (AMEs) produced by bacteria, such as acetyltransferases (AACs), phosphotransferases (APHs), and nucleotidyltransferases (ANTs). Plazomicin was shown to be effective against _Enterobacteriaceae_ in presence of some beta-lactamases. In clinical settings and _in vivo_, bacteria shown to be susceptible toward plazomicin include _Escherichia_ _coli_, _Klebsiella pneumoniae_, _Proteus mirabilis_, and _Enterobacter cloacae_. Other aerobic bacteria that may be affected by plazomicin are _Citrobacter freundii_, _Citrobacter koseri_, _Enterobacter aerogenes_, _Klebsiella oxytoca_, _Morganella morganii_, _Proteus vulgaris_, _Providencia stuartii_, and _Serratia marcescens_.

6'-(hydroxylethyl)-1-(haba)-sisomicin

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients