Plazomicin

Indications

Plazomicin is used for: Complicated Urinary Tract Infections

Adult Dose

Complicated Urinary Tract Infections Indicated for complicated urinary tract infections (cUTIs), including pyelonephritis caused by the following susceptible microorganism(s): Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae Limited clinical safety and efficacy data are currently available, reserve treatment for use in cUTI patients who have limited or no alternative treatment options 15 mg/kg IV q24hr infused over 30 minutes Duration of therapy should be guided by the severity of infection and the patient’s clinical status for up to 7 days; usual duration 4-7 days An appropriate oral therapy may be considered after 4-7 days of therapy to complete a total duration of 7-10 days (IV plus oral); maximum duration of therapy for cUTI is 7 days

Child Dose

<18 years: Safety and efficacy not established

Renal Dose

Renal impairment CrCl >60 to 90 mL/min: 15 mg/kg IV q24hr CrCl >30 to 60 mL/min: 10 mg/kg IV q24hr CrCl >15 to 30 mL/min: 10 mg/kg IV q48hr CrCl <15 mL/min, hemodialysis, or continuous renal replacement: Insufficient information

Administration

IV Preparation Dilute appropriate volume of plazomicin in 0.9% NaCl or lactated Ringer solution to achieve a final volume of 50 mL for IV infusion (final concentration: 2.5-45 mg/mL) Vials do not contain preservatives Follow appropriate aseptic technique in preparing the infusion solution Discard unused portion vial Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit IV Administration Infuse over 30 minutes

Contra Indications

Patients with known hypersensitivity to any aminoglycoside

Precautions

Nephrotoxicity reported; most serum creatinine increases were ≥1 mg/dL above baseline and reversible Ototoxicity may occur Aminoglycosides have been associated with exacerbation of muscle weakness in patients with underlying neuromuscular disorders, or delayed recovery of neuromuscular function in patients receiving concomitant neuromuscular blocking agents Fetal harm may occur when administered to a pregnant woman (see Pregnancy) Serious and occasionally fatal hypersensitivity (anaphylactic) reactions reported in patients receiving aminoglycoside antibacterial drugs; discontinue treatment if an allergic reaction occurs Prescribing a drug in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria

Pregnancy-Lactation

Pregnancy Fetal harm may occur when administered to a pregnant woman There are no available data on this drug in pregnant women to inform a drug-associated risk of adverse developmental outcomes Animal data Published literature reports of streptomycin, an aminoglycoside, state that it can cause total, irreversible, bilateral congenital deafness in children whose mothers received streptomycin during pregnancy No drug-related visceral or skeletal malformations were observed in pregnant rats and rabbits administered subcutaneous plazomicin during organogenesis at maternal exposures ~0.8-fold (rats) and 2.5-fold (rabbits) of the human AUC at the clinical dose of 15 mg/kg/day Auditory function of offspring was not measured in animal studies Advise pregnant women of the potential risk to a fetus Lactation There are no data on the presence of plazomicin in human milk, the effects on the breastfed infant, or the effects on milk production Plazomicin was detected in rat milk Consider developmental and health benefits of breastfeeding along with the mother's clinical need for plazomicin and any potential adverse effects on the breastfed infant from plazomicin or from the underlying maternal condition

Interactions

Adverse Effects

Side effects of Plazomicin : 1-10% Decreased renal function (3.6%) Diarrhea (2.3%) Hypertension (2.3%) Treatment-associated ototoxicity (2.2%) Headache (1.3%) Nausea (1.3%) Vomiting (1.3%) Hypotension (1%) Frequency Not Defined Gastrointestinal disorders: Constipation, gastritis Laboratory investigations: Alanine aminotransferase increased Metabolism and nutrition disorders: Hypokalemia Nervous system disorders: Dizziness Renal and urinary disorders: Hematuria Respiratory, thoracic, and mediastinal disorders: Dyspnea

Mechanism of Action

Plazomicin sulfate is a semisynthetic aminoglycoside antibacterial derived from sisomicin Engineered to overcome aminoglycoside-modifying enzymes (AMEs), the most common aminoglycoside-resistance mechanism in Enterobacteriaceae, and has in vitro activity against extended-spectrum beta-lactamase-producing, aminoglycoside-resistant, and carbapenem-resistant isolates