Version October 2024
Nephrotoxicity has been reported with plazomicin. The risk of nephrotoxicity is greater in patients with impaired renal function, the elderly, and in those receiving concomitant nephrotoxic medications. Assess creatinine clearance in all patients prior to initiating therapy and daily during therapy. Therapeutic Drug Monitoring (TDM) is recommended for complicated urinary tract infection (cUTI) patients with CrCl <90 mL/minute to avoid potentially toxic levels.
Ototoxicity, manifested as hearing loss, tinnitus, and/or vertigo, has been reported with plazomicin. Symptoms of aminoglycoside-associated ototoxicity may be irreversible and may not become evident until after completion of therapy. Aminoglycoside-associated ototoxicity has been observed primarily in patients with a family history of hearing loss, patients with renal impairment, and in patients receiving higher doses and/or longer durations of therapy than recommended.
Aminoglycosides have been associated with neuromuscular blockade. During therapy with plazomicin, monitor for adverse reactions associated with neuromuscular blockade, particularly in high-risk patients, such as patients with underlying neuromuscular disorders (including myasthenia gravis) or in patients concomitantly receiving neuromuscular-blocking agents.
Aminoglycosides, including plazomicin, can cause fetal harm when administered to a pregnant woman.
Note: Aminoglycoside dosing weight: For underweight patients (ie, total body weight [TBW] < ideal body weight [IBW]), calculate the dose based on TBW. For nonobese patients (ie, TBW 1 to 1.25 × IBW), calculate the dose based on TBW or IBW. TBW may be preferred in nonobese patients who may have increased Vd (eg, critically ill). For obese patients (ie, TBW >1.25 x IBW), use adjusted body weight ([0.4 x {TBW-IBW}] + IBW) for initial weight-based dosing and for estimating kidney function with Cockcroft-Gault (CrCl) (Asempa 2019; Pai 2014; Trang 2019; Traynor 1995).
Plague (Y. pestis), treatment (alternative agent) (off-label use):
Note: Consult public health officials for event-specific recommendations.
IV: 15 mg/kg once daily for 7 to 14 days and for at least a few days after clinical resolution (CDC [Nelson 2021]; Stout 2022).
Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms) (alternative agent): Note: Reserve for patients with or at risk for resistant infections (eg, AmpC beta-lactamase– or extended-spectrum beta-lactamase–producing Enterobacterales, carbapenem-resistant Enterobacterales, difficult-to-treat Pseudomonas aeruginosa) (IDSA [Tamma 2023]).
Inpatients: IV: 15 mg/kg once daily. Switch to an appropriate oral regimen once symptoms improve, if culture and susceptibility results allow. Total duration of therapy ranges from 5 to 14 days; for patients with symptomatic improvement within the first 48 to 72 hours of therapy, some experts recommend shorter courses of 5 to 10 days (Connolly 2018; Gupta 2024; Wagenlehner 2019; Yahav 2019).
Outpatients: IV: 15 mg/kg once, followed by 5 to 10 days of appropriate oral therapy (Connolly 2018; Gupta 2024).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: CrCl estimated by Cockcroft-Gault formula using TBW (or IBW for patients with TBW ≥25% IBW)
CrCl ≥60 mL/minute: No dosage adjustment necessary.
CrCl 30 to <60 mL/minute: 10 mg/kg every 24 hours
CrCl 15 to <30 mL/minute: 10 mg/kg every 48 hours
CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
End-stage renal disease (ESRD) requiring hemodialysis: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Continuous renal replacement therapy (CRRT): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Note: For patients with CrCl ≥15 mL/minute to <90 mL/minute, measure plasma trough concentration within 30 minutes prior to second dose. If trough concentration is ≥3 mcg/mL, extend dosing interval by 1.5 fold (ie, from every 24 hours to 36 hours or from every 48 hours to 72 hours).
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
For patients with TBW greater than ideal body weight (IBW) by ≥25%, use adjusted body weight (ABW) for dosing. ABW = IBW + 0.4 x (TBW-IBW).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Cardiovascular: Hypertension (2%), hypotension (1%)
Central nervous system: Headache (1%)
Gastrointestinal: Diarrhea (2%), nausea (1%), vomiting (1%)
Genitourinary: Nephrotoxicity (4%)
Otic: Ototoxicity (2%)
Renal: Increased serum creatinine (4%; CrCl: 30 to 90 mL/minute: ≤10%), acute renal failure (≤4%), decreased creatinine clearance (≤4%), renal disease (≤4%), renal failure syndrome (≤4%), renal insufficiency (≤4%)
Frequency not defined:
Central nervous system: Dizziness
Endocrine & metabolic: Hypokalemia
Gastrointestinal: Constipation, gastritis
Genitourinary: Hematuria
Hepatic: Increased serum alanine aminotransferase
Respiratory: Dyspnea
<1%, postmarketing, and/or case reports: Hypoacusis (reversible), tinnitus (irreversible), vertigo
Hypersensitivity to plazomicin, any aminoglycoside, or any component of the formulation
Concerns related to adverse effects:
• Hypersensitivity reactions: Serious and occasionally fatal hypersensitivity reactions have been reported in patients receiving aminoglycosides; before therapy, inquire about previous hypersensitivity to other aminoglycosides. Discontinue plazomicin if an allergic reaction occurs.
• Nephrotoxicity: [US Boxed Warning]: May cause nephrotoxicity; risk factors include preexisting renal impairment, elderly patients, and concomitant nephrotoxic agents. Monitor renal function closely and reassess continuation of therapy if nephrotoxicity occurs. Most serum creatinine increases were ≤1 mg/dL above baseline and usually reversible; increases mainly occurred in patients with CrCl ≤90 mg/dL and were associated with plazomicin trough concentrations ≥3 mcg/mL.
• Neuromuscular blockade: [US Boxed Warning]: May cause neuromuscular blockade, especially in patients with underlying neuromuscular disorders and/or in patients receiving concomitant neuromuscular blocking agents.
• Ototoxicity: [US Boxed Warning]: May cause ototoxicity manifested as hearing loss, tinnitus, and/or vertigo; risk factors include family history of hearing loss, renal impairment, and receipt of higher doses and/or longer durations of therapy than recommended. Symptoms of ototoxicity may be irreversible and may not become evident until after therapy is complete.
• Superinfection: May cause superinfection of Clostridioides difficile infection (CDI) and pseudomembranous colitis; CDI has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Hearing impairment: Use with caution in patients with hearing loss or a family history of hearing loss.
• Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis.
• Renal impairment: Use with caution in patients with preexisting renal insufficiency; dosage modification required.
Special populations:
• Patients with genomic variants in MT-RNR1: Carriers of certain variants in the MT-RNR1 gene (eg, m.1555A>G) may be at increased risk for aminoglycoside-induced ototoxicity, including potentially significant hearing loss that may be irreversible, even when serum levels are within the normal range.
• Pregnancy: [US Boxed Warning]: Aminoglycosides may cause fetal harm if administered to a pregnant woman.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as sulfate:
Zemdri: 500 mg/10 mL (10 mL)
Solution, Intravenous, as sulfate [preservative free]:
Zemdri: 500 mg/10 mL (10 mL)
No
Solution (Zemdri Intravenous)
500 mg/10 mL (per mL): $41.51
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IV: Infuse over 30 minutes.
Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms): Treatment of complicated urinary tract infections (UTI), including pyelonephritis caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae in patients ≥18 years. Note: Reserve for use in complicated UTI patients who have limited or no alternative treatment options.
Plague (Yersinia pestis), treatment
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminoglycosides: May enhance the nephrotoxic effect of other Aminoglycosides. Aminoglycosides may enhance the neurotoxic effect of other Aminoglycosides. Risk X: Avoid combination
Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Amphotericin B may enhance the neurotoxic effect of Aminoglycosides. Risk C: Monitor therapy
Ataluren: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, an increased risk of nephrotoxicity may occur with the concomitant use of ataluren and aminoglycosides. Risk X: Avoid combination
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
Bacitracin (Systemic): May enhance the nephrotoxic effect of Aminoglycosides. Bacitracin (Systemic) may enhance the neurotoxic effect of Aminoglycosides. Risk X: Avoid combination
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Aminoglycosides may enhance the nephrotoxic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy
Botulinum Toxin-Containing Products: Aminoglycosides may enhance the neuromuscular-blocking effect of Botulinum Toxin-Containing Products. Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy
CARBOplatin: May enhance the nephrotoxic effect of Aminoglycosides. Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy
Cephalosporins: May enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. CISplatin may enhance the neurotoxic effect of Aminoglycosides. Risk X: Avoid combination
Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Management: Avoid coadministration of colistimethate and aminoglycosides whenever possible due to the risk of nephrotoxicity and neuromuscular blockade. If coadministration cannot be avoided, monitor renal and neuromuscular function. Risk D: Consider therapy modification
Cyclizine: May enhance the ototoxic effect of Aminoglycosides. Risk C: Monitor therapy
CycloSPORINE (Systemic): Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Risk C: Monitor therapy
Distigmine: Aminoglycosides may diminish the therapeutic effect of Distigmine. Risk C: Monitor therapy
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Foscarnet: May enhance the nephrotoxic effect of Aminoglycosides. Risk X: Avoid combination
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Mannitol (Systemic): May enhance the nephrotoxic effect of Aminoglycosides. Risk X: Avoid combination
Mecamylamine: Aminoglycosides may enhance the neuromuscular-blocking effect of Mecamylamine. Risk X: Avoid combination
Methoxyflurane: Aminoglycosides may enhance the nephrotoxic effect of Methoxyflurane. Risk X: Avoid combination
Mycophenolate: Antibiotics may decrease serum concentrations of the active metabolite(s) of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor therapy
Netilmicin (Ophthalmic): Aminoglycosides may enhance the nephrotoxic effect of Netilmicin (Ophthalmic). Risk X: Avoid combination
Neuromuscular-Blocking Agents: Aminoglycosides may enhance the therapeutic effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
Oxatomide: May enhance the ototoxic effect of Aminoglycosides. Risk C: Monitor therapy
Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor therapy
Polymyxin B: May enhance the nephrotoxic effect of Aminoglycosides. Polymyxin B may enhance the neurotoxic effect of Aminoglycosides. Risk X: Avoid combination
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Tacrolimus (Systemic): Aminoglycosides may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Tenofovir Products: Aminoglycosides may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Vancomycin may enhance the neurotoxic effect of Aminoglycosides. Management: Consider avoiding coadministration of aminoglycosides and vancomycin unless clinically indicated. If coadministered, monitor closely for signs of nephrotoxicity and neurotoxicity. Risk D: Consider therapy modification
Aminoglycosides may cause fetal harm if administered to a pregnant patient. There are several reports of total irreversible bilateral congenital deafness in children whose mothers received another aminoglycoside (streptomycin) during pregnancy. Although serious side effects to the fetus/infant have not been reported following maternal use of all aminoglycosides, a potential for harm exists.
Plazomicin is used in the management of plague (Y. pestis). Untreated infections in pregnant patients may result in hemorrhage (including postpartum hemorrhage), maternal and fetal death, preterm birth, and stillbirth. Limited data suggest maternal-fetal transmission of Y. pestis can occur if not treated. Pregnant patients should be treated for Y. pestis; parenteral antibiotics are preferred for initial treatment when otherwise appropriate. Plazomicin is an alternative aminoglycoside recommended for use (in combination with a fluroquinolone) for treating pregnant patients with bubonic, pharyngeal, pneumonic, or septicemic plague (CDC [Nelson 2021]).
It is not known if plazomicin is present in breast milk.
As a class, aminoglycosides are expected to be poorly distributed into breast milk, limiting systemic exposure to a nursing infant. In general, modification of bowel flora may occur with any antibiotic exposure (Chung 2002). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Urinalysis, urine output, BUN, serum creatinine (prior to initiation of therapy and daily during therapy), plasma plazomicin trough (for patients with CrCl <90 mL/min); symptoms of ototoxicity or neuromuscular blockade
Trough <3 mcg/mL; measure plasma trough concentration within 30 minutes prior to second dose.
Interferes with bacterial protein synthesis by binding to 30S ribosomal subunit resulting in a defective bacterial cell membrane.
Distribution: 0.24 +/- 0.04 L/kg (Cass 2011)
Protein binding: ~20%
Half-life elimination: 3 to 4 hours (Cass 2011)
Time to peak: IV: At the end of or just after infusion (Cass 2011)
Excretion: Urine (97.5% as unchanged drug); feces (<0.2%); Clearance: 1.1 ± 0.1 mL/minute/kg (Cass 2011)
Altered kidney function: AUC is increased and clearance is decreased in renal impairment.
Anti-infective considerations:
Parameters associated with efficacy: Gram-negative bacilli: Concentration-dependent; associated with AUC24/minimum inhibitory concentration (MIC); goal: ≥18 to 24 (bacteriostatic) or ≥73 to 85 (bactericidal; serious infections); AUC24: 210 to 315 mg•hour/L has been targeted for carbapenem-resistant Enterobacteriaceae (Kuti 2019; Noel 2019; Shaeer 2019).
Expected drug exposures in adults with normal renal function: AUC24: 15 mg/kg: ~225 to 265 mg•hour/L (Kuti 2019; Shaeer 2019; manufacturer's labeling).
Parameters associated with toxicity: Nephrotoxicity is associated with elevated Cmin (trough) concentrations (≥2 to 3 mg/L) (Shaeer 2019; manufacturer's labeling).
Postantibiotic effect: Bacterial killing continues after plazomicin concentration drops below the MIC of targeted pathogen; generally ~0.2 to 2.6 hours, though the actual time of postantibiotic effect varies with organism and plazomicin Cmax (peak) (Shaeer 2019; manufacturer's labeling).
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