Plazomicin Dosing Recommendations
The recommended dose of plazomicin is 15 mg/kg intravenously every 24 hours for adults with normal renal function, with dose adjustments required for renal impairment. 1
Standard Adult Dosing
Plazomicin 15 mg/kg IV every 24 hours is the established dose for treating complicated urinary tract infections (cUTI) in adults with normal renal function, administered for 4-7 days. 2
For plague treatment (as an alternative agent), the same dose of 15 mg/kg IV every 24 hours is recommended for both bubonic/pharyngeal and pneumonic/septicemic forms. 1
For carbapenem-resistant Enterobacterales (CRE) complicated urinary tract infections, plazomicin 15 mg/kg IV every 12 hours is recommended for 5-7 days. 1
Pediatric Dosing
- Pediatric dosing information for plazomicin is not established in the available guidelines, as the drug is only FDA-approved for adult patients with limited or no alternative treatment options. 2
Renal Impairment Adjustments
Dose reduction is mandatory for patients with moderate or severe renal impairment (creatinine clearance <60 mL/min). 3
Patients with moderate renal impairment (CrCl 30-59 mL/min) should receive 8-12 mg/kg IV every 24 hours. 4
Patients with severe renal impairment experience 4.42-fold higher drug exposures compared to those with normal renal function, necessitating further dose reduction. 4
Plazomicin is not recommended for patients with severe renal impairment requiring renal replacement therapy due to insufficient safety and efficacy data. 2
Therapeutic Drug Monitoring
Trough concentration monitoring is essential for all patients with any degree of renal impairment (mild, moderate, or severe) to prevent nephrotoxicity. 3
The target trough concentration threshold is <3 μg/mL to reduce nephrotoxicity risk while maintaining efficacy. 3, 5
Trough concentrations should be measured to prevent serum creatinine increases ≥0.5 mg/dL above baseline. 5
The Hartford nomogram can be applied to optimize dosing intervals (extending to every 36 or 48 hours when appropriate) based on 10-hour post-dose concentrations, which reduces the proportion of patients with elevated troughs while maintaining therapeutic AUC ranges of 121-368 μg·h/mL. 5
Administration Details
Plazomicin should be administered as a 30-minute intravenous infusion. 4
The pharmacokinetic profile shows a maximum concentration of 113 μg/mL, AUC₀₋₂₄ of 239 h·μg/mL, half-life of 4.0 hours, and steady-state volume of distribution of 0.24 L/kg after a 15 mg/kg dose. 6
Important Safety Considerations
Like all aminoglycosides, plazomicin carries risks of nephrotoxicity, ototoxicity, neuromuscular blockade, and fetal harm in pregnancy. 2
Total drug clearance declines proportionally with declining renal function, making dose adjustments critical to prevent toxicity. 4
The drug demonstrates concentration-dependent bactericidal activity against multidrug-resistant gram-negative organisms, including those with aminoglycoside-modifying enzymes, but is inactive against organisms with ribosomal methyltransferases. 2, 6