Skip to main content

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, 2024. Written by ASHP.

Warning

    Nephrotoxicity
  • Nephrotoxicity reported. Greater risk in patients with impaired renal function, geriatric patients, and those receiving nephrotoxic drugs concomitantly.

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

  • Therapeutic drug monitoring recommended for patients with Clcr <90 mL/minute to avoid toxic concentrations.

    Ototoxicity
  • Ototoxicity, manifested as hearing loss, tinnitus, and/or vertigo, reported.

  • Aminoglycoside-associated ototoxicity observed primarily in patients with family history of hearing loss, patients with renal impairment, and those receiving higher doses and/or longer durations of aminoglycoside therapy than recommended.

  • Symptoms may be irreversible and may not become evident until after completion of aminoglycoside therapy.

    Neuromuscular Blockade
  • Aminoglycosides are associated with neuromuscular blockade.

  • 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.

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

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

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 Clcr ≥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 Clcr 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 Clcr 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%.

Table 1. Plazomicin Dosage for Adults with Renal Impairment1

Clcr (mL/minute)

Plazomicin Dosage

60–89

15 mg/kg once every 24 hours

30–59

10 mg/kg once every 24 hours

15–29

10 mg/kg once every 48 hours

Data insufficient to recommend a dosage for patients with Clcr <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

Warnings/Precautions

Warnings

Nephrotoxicity

Nephrotoxicity reported. In most cases, Scr 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 Clcr 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 Clcr 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 Clcr daily and adjust dosage accordingly. Data insufficient to recommend dosage in patients with Clcr <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 Clcr 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

Drug

Interaction

Ceftazidime

In vitro evidence of synergistic antibacterial effects with plazomicin against some Enterobacteriaceae; clinical importance not known

Clindamycin

No in vitro evidence of antagonistic antibacterial effects with plazomicin against Enterobacteriaceae

Colistin

Some in vitro evidence of synergistic antibacterial effects with plazomicin against some K. pneumoniae; no in vitro evidence of antagonistic antibacterial effects against Enterobacteriaceae

Daptomycin

No in vitro evidence of antagonistic antibacterial effects with plazomicin against Enterobacteriaceae

Fosfomycin

Some in vitro evidence of synergistic antibacterial effects with plazomicin against some K. pneumoniae; no in vitro evidence of antagonistic antibacterial effects against Enterobacteriaceae

Levofloxacin

No in vitro evidence of antagonistic antibacterial effects with plazomicin against Enterobacteriaceae

Linezolid

No in vitro evidence of antagonistic antibacterial effects with plazomicin against Enterobacteriaceae

Meropenem

In vitro evidence of synergistic antibacterial effects with plazomicin against some Enterobacteriaceae; clinical importance not known

Metformin

No effects on metformin pharmacokinetics

Piperacillin and tazobactam

In vitro evidence of synergistic antibacterial effects with plazomicin against some Enterobacteriaceae; clinical importance not known

Rifampin

No in vitro evidence of antagonistic antibacterial effects with plazomicin against Enterobacteriaceae

Tigecycline

No in vitro evidence of antagonistic antibacterial effects with plazomicin against Enterobacteriaceae

Vancomycin

No in vitro evidence of antagonistic antibacterial effects with plazomicin against Enterobacteriaceae

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 Clcr of 15 to <60 mL/minute compared with those with Clcr ≥60 mL/minute. Following single 7.5-mg/kg IV dose in adults with mild (Clcr 60 to <90 mL/minute), moderate (Clcr 30 to <60 mL/minute), or severe (Clcr 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

Compatible

Ringer's injection, lactated

Sodium chloride 0.9%

Drug Compatibility
Y-Site Compatibility

Compatible

Ampicillin sodium and sulbactam sodium

Azithromycin

Aztreonam

Bumetanide

Calcium gluconate

Caspofungin acetate

Cefazolin sodium

Cefepime HCl

Cefoxitin sodium

Ceftaroline fosamil

Ceftazidime

Ceftazidime and avibactam sodium

Ceftolozane sulfate and tazobactam sodium

Ceftriaxone sodium

Cefuroxime sodium

Ciprofloxacin

Cisatracurium besylate

Colistimethate sodium

Dexamethasone sodium phosphate

Dexmedetomidine HCl

Digoxin

Diltiazem HCl

Diphenhydramine HCl

Dobutamine HCl

Dopamine HCl

Doripenem

Doxycycline hyclate

Epinephrine

Eptifibatide

Ertapenem sodium

Esmolol HCl

Famotidine

Fentanyl citrate

Fluconazole

Fosphenytoin sodium

Furosemide

Hydrocortisone sodium succinate

Hydromorphone HCl

Imipenem and cilastatin sodium

Insulin, regular

Isavuconazonium sulfate

Labetalol HCl

Lidocaine HCl

Linezolid

Lorazepam

Magnesium sulfate

Mannitol

Meperidine HCl

Meropenem

Meropenem and vaborbactam

Mesna

Metoclopramide HCl

Metronidazole

Midazolam HCl

Milrinone lactate

Morphine sulfate

Naloxone HCl

Nicardipine HCl

Nitroglycerin

Norepinephrine bitartrate

Octreotide acetate

Ondansetron HCl

Pantoprazole

Penicillin G potassium

Phenylephrine HCl

Piperacillin sodium and tazobactam sodium

Potassium chloride

Potassium phosphates

Ranitidine HCl

Rocuronium bromide

Sodium bicarbonate

Sodium nitroprusside

Sodium phosphates

Tedizolid phosphate

Tigecycline

Vancomycin HCl

Vasopressin

Vecuronium bromide

Incompatible

Albumin human

Amiodarone HCl

Amphotericin B

Anidulafungin

Calcium chloride

Daptomycin

Esomeprazole sodium

Heparin sodium

Levofloxacin

Methylprednisolone sodium succinate

Micafungin sodium

Phenytoin sodium

Propofol

Actions and Spectrum

Advice to Patients

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.

Plazomicin Sulfate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Concentrate, for injection, for IV infusion only

50 mg (of plazomicin) per mL

Zemdri

Achoagen

AHFS DI Essentials™. © Copyright 2024, Selected Revisions January 20, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

Reload page with references included

Frequently asked questions