Plazomicin (Monograph)

Brand name: Zemdri
Drug class: Aminoglycosides
Chemical name: (2S)-4-amino-N-[(1R,2S,3S,4R,5S)-5-amino-4-[[(2S,3R)-3-amino-6-[(2-hydroxyethylamino)methyl]-3,4-dihydro-2H-pyran-2-yl]oxy]-2-[(2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-(methylamino)oxan-2-yl]oxy-3-hydroxycyclohexyl]-2-hydroxybutanamide;sulfuric acid
Molecular formula: C₂₅H₄₈N₆O₁₀•2.5H₂SO₄
CAS number: 1380078-95-4

Medically reviewed by Drugs.com on Jan 10, 2025. Written by ASHP.

Introduction

Antibacterial; semisynthetic aminoglycoside derived from sisomicin.

Uses for Plazomicin

Urinary Tract Infections

Treatment of complicated urinary tract infections (including pyelonephritis) caused by susceptible Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Enterobacter cloacae.

Only limited clinical efficacy and safety data available; reserve for use in patients with limited or no alternative treatment options.

Plazomicin Dosage and Administration

General

• Assess Cl_cr in all patients prior to initiating plazomicin and daily during therapy with the drug.

• Calculate Cl_cr using Cockcroft-Gault formula and total body weight. For patients with total body weight exceeding ideal body weight by ≥25%, use ideal body weight to calculate Cl_cr.

• Plazomicin therapeutic drug monitoring recommended in patients with renal impairment. (See Renal Impairment under Dosage and Administration.)

Administration

IV Administration

Administer by IV infusion.

For solution and drug compatibility information, see Compatibility under Stability.

Dilution

Available as concentrate containing 50 mg of plazomicin per mL. Must dilute concentrate prior to administration.

Withdraw appropriate volume of plazomicin concentrate that will provide the recommended dose from appropriate number of vials. Dilute in 0.9% sodium chloride injection or lactated Ringer's injection to achieve final volume of 50 mL.

Rate of Administration

Administer by IV infusion over 30 minutes.

Dosage

Commercially available as plazomicin sulfate; dosage expressed in terms of plazomicin.

Calculate dosage using total body weight. For patients with total body weight exceeding ideal body weight by ≥25%, use adjusted body weight.

Adults

Complicated Urinary Tract Infections

IV

Adults with Cl_cr ≥90 mL/minute: 15 mg/kg once every 24 hours for 4–7 days. May then switch to appropriate oral antibacterial to complete total treatment duration of 7–10 days.

Select duration of treatment based on severity of infection and clinical status. Total treatment duration (IV and oral) is 7–10 days.

Prescribing Limits

Adults

Complicated Urinary Tract Infections

IV

Maximum duration: 7 days.

Special Populations

Renal Impairment

Complicated Urinary Tract Infections

IV

Adjust dosage based on degree of renal impairment. (See Table 1.)

Therapeutic drug monitoring recommended in all patients with Cl_cr of 15 to <90 mL/minute. Measure trough plasma concentrations 30 minutes prior to second dose. If plasma concentrations are ≥3 mcg/mL, extend dosing interval by 1.5-fold (i.e., from once every 24 hours to once every 36 hour or from once every 48 hours to once every 72 hours). Use therapeutic drug monitoring to ensure that trough plasma concentrations remain <3 mcg/mL.

Calculate Cl_cr using Cockcroft-Gault formula and total body weight; use ideal body weight for patients with total body weight exceeding ideal body weight by ≥25%.

Calculate doses using total body weight; use adjusted body weight for patients with total body weight exceeding ideal body weight by ≥25%.

Data insufficient to recommend a dosage for patients with Cl_cr <15 mL/minute or patients receiving renal replacement therapy, including hemodialysis or continuous renal replacement therapy.

Geriatric Patients

Dosage adjustments based solely on age not needed. Select dosage with caution because of age-related decreases in renal function; monitor plazomicin concentrations as appropriate. (See Geriatric Use under Cautions.)

Cautions for Plazomicin

Contraindications

• Known hypersensitivity to any aminoglycoside.

Warnings/Precautions

Warnings

Nephrotoxicity

Nephrotoxicity reported. In most cases, S_cr increased above baseline by ≤1 mg/dL and was reversible. Increased risk in patients with impaired renal function, geriatric patients, and patients receiving concomitant nephrotoxic drugs.

Assess Cl_cr in all patients prior to initiating plazomicin and daily during therapy with the drug. In patients with worsening renal function, assess benefits of continuing plazomicin.

To avoid potentially toxic concentrations, therapeutic drug monitoring recommended for patients with Cl_cr 15 to <90 mL/minute. (See Renal Impairment under Dosage and Administration.)

Ototoxicity

Ototoxicity, manifested as hearing loss, tinnitus, and/or vertigo, reported. Symptoms of aminoglycoside-associated ototoxicity may be irreversible and may not become evident until after completion of aminoglycoside therapy.

Aminoglycoside-associated ototoxicity primarily observed in patients with a family history of hearing loss (excluding age-related hearing loss), patients with renal impairment, and patients receiving higher doses and/or longer durations of aminoglycoside therapy than recommended. Consider risks and benefits of plazomicin in such patients.

Neuromuscular Blockade

Aminoglycosides are associated with neuromuscular blockade (e.g., exacerbation of muscle weakness in patients with underlying neuromuscular disorders, delay in recovery of neuromuscular function in patients receiving neuromuscular blocking agents concomitantly).

Monitor for adverse effects associated with neuromuscular blockade, particularly in high-risk patients (e.g., those with underlying neuromuscular disorders, including myasthenia gravis) and in those receiving neuromuscular blocking agents concomitantly.

Fetal/Neonatal Morbidity

Aminoglycosides, including plazomicin, can cause fetal harm when administered to pregnant women. Aminoglycosides cross the placenta, and streptomycin has been associated with several reports of total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero. (See Pregnancy under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported in patients receiving aminoglycosides.

Prior to initiation of plazomicin, carefully inquire about previous hypersensitivity reactions to aminoglycosides. Cross-sensitivity among aminoglycosides established. Therefore, use of plazomicin contraindicated in patients with history of hypersensitivity to any aminoglycoside.

Discontinue plazomicin if an allergic reaction occurs.

Other Warnings and Precautions

C. difficile Diarrhea and Colitis

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridioides difficile (formerly known as Clostridium difficile). C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including plazomicin, and may range in severity from mild diarrhea to fatal colitis. C. difficile produces toxins A and B which contribute to development of CDAD; hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.

Consider CDAD if diarrhea develops during or after therapy and manage accordingly. Obtain careful medical history since CDAD may occur as late as ≥2 months after anti-infective therapy is discontinued.

If CDAD suspected or confirmed, discontinue anti-infectives not directed against C. difficile as soon as possible. Initiate appropriate anti-infective therapy directed against C. difficile (e.g., vancomycin, fidaxomicin, metronidazole), supportive therapy (e.g., fluid and electrolyte management, protein supplementation), and surgical evaluation as clinically indicated.

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of plazomicin and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria. Prescribing plazomicin in the absence of proven or strongly suspected bacterial infection unlikely to provide benefit to the patient and increases risk of development of drug-resistant bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

Information on test methods and quality control standards for in vitro susceptibility testing of antibacterial agents and specific interpretive criteria for such testing recognized by FDA is available at [Web].

Specific Populations

Pregnancy

Aminoglycosides, including plazomicin, can cause fetal harm when administered to pregnant women. (See Fetal/Neonatal Morbidity under Cautions.)

No data on use of plazomicin in pregnant women.

In animals, no plazomicin-related visceral or skeletal malformations observed; auditory function of offspring in animal studies not measured.

Lactation

Distributed into milk in rats. Not known if plazomicin distributes into human milk, affects breast-fed infant, or affects milk production.

Consider developmental and health benefits of breast-feeding along with the mother's clinical need for plazomicin and any potential adverse effects on the breast-fed infant from the drug or the underlying maternal condition.

Pediatric Use

Safety and efficacy not established in patients <18 years of age.

Geriatric Use

Since risk of adverse effects may be greater in patients with renal impairment and geriatric patients are more likely to have decreased renal function, carefully select dosage in geriatric patients and monitor renal function. Take into account renal function and plazomicin plasma concentrations as appropriate. (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Systemic clearance of plazomicin not expected to be affected by hepatic impairment.

Renal Impairment

Monitor Cl_cr daily and adjust dosage accordingly. Data insufficient to recommend dosage in patients with Cl_cr <15 mL/minute or in those receiving renal replacement therapy, including hemodialysis or continuous renal replacement therapy.

Therapeutic drug monitoring of trough plasma concentrations recommended in patients with Cl_cr of 15 to <90 mL/minute; adjust dosage accordingly. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Decreased renal function, diarrhea, hypertension, headache, nausea, vomiting, hypotension, dizziness.

Drug Interactions

Drugs Metabolized by Hepatic Microsomal Enzymes

Does not inhibit CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4/5.

Does not induce CYP1A2, 2B6, or 3A4.

Drugs Affecting or Affected by Membrane Transporters

Not a substrate of P-glycoprotein (P-gp) transport or breast cancer resistance protein (BCRP).

Does not inhibit P-gp, BCRP, bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), organic anion transport polypeptide (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 1, or OCT2.

Selectively inhibits multidrug and toxin extrusion (MATE) 1 and MATE2-K renal transporter.

Nephrotoxic Drugs

Risk of nephrotoxicity increased in patients receiving nephrotoxic drugs concomitantly. (See Nephrotoxicity under Cautions.)

Neuromuscular Blocking Agents

Concomitant use of neuromuscular blocking agents and aminoglycosides associated with delay in recovery of neuromuscular function. (See Neuromuscular Blockade under Cautions.)

Monitor for adverse reactions associated with neuromuscular blockade if neuromuscular blocking agent used concomitantly with plazomicin.

Specific Drugs

Plazomicin Pharmacokinetics

Absorption

Plasma Concentrations

No appreciable accumulation following multiple IV doses (15 mg/kg once every 24 hours) in healthy adults with normal renal function; steady-state trough plasma concentrations attained after second dose.

Peak and trough plasma concentrations increase proportionally over doses ranging from 4–15 mg/kg.

Special Populations

Hepatic impairment: Pharmacokinetics not studied.

Renal impairment: Total body clearance substantially decreased in patients with Cl_cr of 15 to <60 mL/minute compared with those with Cl_cr ≥60 mL/minute. Following single 7.5-mg/kg IV dose in adults with mild (Cl_cr 60 to <90 mL/minute), moderate (Cl_cr 30 to <60 mL/minute), or severe (Cl_cr 15 to <30 mL/minute) renal impairment, AUC is 1.01-, 1.98-, or 4.42-fold higher, respectively, compared with those with normal renal function.

Geriatric patients: No clinically relevant age-related trends in exposures observed. Elevated trough plasma concentrations reported in geriatric patients 65–90 years of age were primarily attributed to age-related changes in renal function.

Distribution

Plasma Protein Binding

Approximately 20%; in vitro, protein binding independent of concentration over range of 5–100 mcg/mL.

Elimination

Metabolism

Not metabolized.

Elimination Route

97.5% of an IV dose eliminated in urine as unchanged drug.

Half-life

Healthy adults with normal renal function: 3.5 hours.

Patients with complicated urinary tract infections and blood stream infections: 4–5 hours.

Stability

Storage

Parenteral

Concentrate for IV Infusion

Vials: 2–8°C.

Diluted solutions containing 2.5–45 mg/mL prepared using 0.9% sodium chloride or lactated Ringer's: Stable for 24 hours at room temperature.

Compatibility

Parenteral

Solution Compatibility1 18 HID

Drug Compatibility

Actions and Spectrum

• Aminoglycoside derived from sisomicin. Has expanded spectrum of activity compared with other commercially available aminoglycosides because of certain structural modifications that result in activity against many bacteria possessing aminoglycoside-modifying enzymes that inactive most other aminoglycosides (e.g., amikacin, gentamicin, tobramycin).

• Exhibits concentration-dependent bactericidal activity against susceptible bacteria. Like other aminoglycosides, binds to 16S rRNA of the bacterial 30S ribosomal subunit, resulting in inhibition of bacterial protein synthesis.

• Enterobacteriaceae: Active in vitro and in clinical infections against E. coli, K. pneumoniae, P. mirabilis, and E. cloacae.

• Also active in vitro against other Enterobacteriaceae, including some strains of Citrobacter freundii, C. koseri, E. aerogenes, K. oxytoca, Morganella morganii, P. vulgaris, Providencia stuartii, and Serratia marcescens; clinical importance of this in vitro activity not known and efficacy in treating clinical infections caused by these bacteria not established.

• Other gram-negative aerobic bacteria: Active in vitro against Brucella, Francisella tularensis, and Yersinia pestis. Although some strains of Acinetobacter and Pseudomonas aeruginosa may be susceptible in vitro, Acinetobacter, Ps. aeruginosa, and Stenotrophomonas maltophilia generally resistant.

• Gram-positive bacteria: Although clinical importance not known, active in vitro against many staphylococci (including methicillin-resistant Staphylococcus aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA]). Streptococci (including Streptococcus pneumoniae) and enterococci (including Enterococcus faecalis and E. faecium) are resistant.

• Anaerobes: Inactive against anaerobic bacteria.

• Resistance to aminoglycosides can occur as the result of bacterial aminoglycoside-modifying enzymes, alterations in ribosomal target binding site because of presence of 16S rRNA methyltransferases, up-regulation of bacterial efflux pumps, and/or reduced permeability of bacterial cells because of loss of outer membrane porins.

• Most common mechanism of resistance to aminoglycosides in Enterobacteriaceae is presence of aminoglycoside-modifying enzymes. Plazomicin not inactivated by most aminoglycoside-modifying enzymes (e.g., acetyltransferases, phosphotransferases, nucleotidyltransferases) that inactivate other commercially available aminoglycosides and is active against many multidrug-resistant (MDR) Enterobacteriaceae resistant to other aminoglycosides (e.g., amikacin, gentamicin, tobramycin). Active against Enterobacteriaceae that possess certain β-lactamases, including extended-spectrum β-lactamases (e.g., TEM, SHV, CTX-M, AmpC), serine carbapenemases (e.g., KPC-2, KPC-3), and oxacillinase (e.g., OXA-48).

• Like other aminoglycosides, plazomicin not active against Enterobacteriaceae and other bacteria (e.g., Acinetobacter, Ps. aeruginosa) that produce 16S rRNA methyltransferases. Bacteria producing metallo-β-lactamases often co-express 16S rRNA methyltransferase, conferring resistance to plazomicin.

• May have reduced activity against Enterobacteriaceae with overexpression of certain efflux pumps (e.g., acrAB-tolC) or lower expression of porins (e.g., ompF, ompK36).

Advice to Patients

• Advise patients that antibacterials, including plazomicin, should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).

• Importance of completing full course of therapy, even if feeling better after a few days.

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with plazomicin or other antibacterials in the future.

• Advise patients that nephrotoxicity has been reported with plazomicin therapy. Importance of following clinician directions regarding renal function laboratory testing, maintenance of adequate hydration, and avoidance of potentially nephrotoxic agents while receiving plazomicin.

• Advise patients that hearing loss, vertigo, and tinnitus have been reported with plazomicin therapy. Importance of patients informing a clinician if they experience changes in hearing or balance, the onset of symptoms of tinnitus (e.g., buzzing or roaring in the ear), or a change in symptoms of preexisting tinnitus, even if such effects occur after completion of plazomicin therapy.

• Advise patients that aggravation of muscle weakness has been reported with other aminoglycosides, particularly in patients with underlying neuromuscular disease or concomitant therapy with neuromuscular blocking agents. Importance of patients informing a clinician if they have an underlying neuromuscular disorder (e.g., myasthenia gravis) or are receiving neuromuscular blocking agents.

• Advise patients that allergic reactions, including serious allergic reactions, could occur and that serious reactions require immediate treatment. Importance of informing clinician about any previous hypersensitivity reactions to plazomicin or other aminoglycosides.

• Advise patients that diarrhea is a common problem caused by anti-infectives, including plazomicin. Importance of contacting a clinician if severe watery and bloody diarrhea occurs during or as late as 2 months or longer after the last dose.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed. Advise women of childbearing potential that aminoglycosides, including plazomicin, can cause fetal harm (e.g., irreversible congenital deafness) if administered during pregnancy. Importance of contacting a clinician if they become pregnant while taking plazomicin.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Reload page with references included

Frequently asked questions

• What type of drug is Zemdri?

Medical Disclaimer