ZEMDRI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZEMDRI (ZEMDRI).
ZEMDRI (plazomicin) is an aminoglycoside antibacterial that binds to the bacterial 30S ribosomal subunit, inhibiting protein synthesis.
| Metabolism | Not significantly metabolized; primarily excreted unchanged in urine via glomerular filtration. |
| Excretion | Approximately 70% of ZEMDRI (plazomicin) is eliminated unchanged in the urine via glomerular filtration, with about 20% excreted in feces. Less than 5% is metabolized. Renal clearance accounts for >85% of total clearance. |
| Half-life | Terminal elimination half-life is approximately 5.6 hours in patients with normal renal function (CrCl ≥90 mL/min). Half-life is prolonged in renal impairment, ranging up to 20 hours in severe impairment (CrCl <30 mL/min). Clinical context: Dosing interval adjustments are required based on creatinine clearance. |
| Protein binding | Approximately 15-20% bound to human plasma proteins, predominantly albumin. Binding is low and not concentration-dependent. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 0.5 L/kg (range 0.3-0.8 L/kg). This indicates distribution primarily into extracellular fluid. Clinical meaning: Equivalent to total body water; does not penetrate well into CNS or ocular tissues. |
| Bioavailability | Bioavailability is 100% for intravenous route. Oral bioavailability is negligible (<1%) due to poor absorption; therefore, only IV administration is clinically relevant. |
| Onset of Action | Intravenous administration: Onset of bactericidal activity is immediate after infusion begins, but time to effective plasma concentrations (Cmax/MIC ratio) is typically within 1 hour post-infusion. Time to clinical response varies but serum levels reach peak at end of 30-minute infusion. |
| Duration of Action | Duration of action is primarily dependent on concentration-dependent killing. For susceptible pathogens, plasma concentrations remain above MIC for the entire dosing interval (approx 24 hours) with once-daily dosing in patients with normal renal function. Clinical notes: Post-antibiotic effect (PAE) is minimal for Gram-positive but prolonged (2-4 hours) for Gram-negative organisms. |
15 mg/kg intravenously over 30 minutes every 24 hours.
| Dosage form | SOLUTION |
| Renal impairment | For creatinine clearance (CrCl) 30-89 mL/min: 15 mg/kg every 48 hours. For CrCl <30 mL/min or on hemodialysis: 15 mg/kg as a single loading dose followed by 7.5 mg/kg every 48 hours. For patients receiving continuous renal replacement therapy: 15 mg/kg every 24 hours. |
| Liver impairment | No dose adjustment recommended for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not approved for pediatric patients. Safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; select dose based on renal function as elderly patients often have reduced creatinine clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZEMDRI (ZEMDRI).
| Breastfeeding | It is unknown whether plazomicin is excreted in human milk. M/P ratio not available. Due to the potential for adverse effects in the nursing infant, a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | ZEMDRI (plazomicin) is an aminoglycoside antibiotic. Animal studies have not been conducted; however, aminoglycosides are known to cross the placenta and may cause fetal nephrotoxicity and ototoxicity. Use during pregnancy only if clearly needed. First trimester: limited data, potential for harm. Second and third trimesters: risk of fetal hearing and renal impairment. |
■ FDA Black Box Warning
Nephrotoxicity, ototoxicity, neuromuscular blockade, and fetal harm.
| Serious Effects |
Hypersensitivity to plazomicin or any aminoglycoside.
| Precautions | Nephrotoxicity, ototoxicity (including hearing loss and vestibular toxicity), neuromuscular blockade, hypersensitivity reactions, and Clostridioides difficile-associated diarrhea. |
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| Fetal Monitoring | Monitor maternal renal function (serum creatinine, BUN) and hearing (audiometry) before and during therapy. Monitor fetal growth and well-being with ultrasound if used in pregnancy. Assess for signs of ototoxicity or nephrotoxicity in the neonate after delivery. |
| Fertility Effects | No human data on fertility effects. In animal studies, aminoglycosides have been associated with testicular damage and impaired fertility at high doses; relevance to humans unknown. |