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Plazomicin

Medically reviewed by Drugs.com. Last updated on Mar 10, 2020.

Pronunciation

(pla zoe MYE sin)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous, as sulfate [preservative free]:

Zemdri: 500 mg/10 mL (10 mL)

Brand Names: U.S.

  • Zemdri

Pharmacologic Category

  • Antibiotic, Aminoglycoside

Pharmacology

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)

Excretion

Urine (97.5% as unchanged drug); feces (<0.2%)

Clearance: 1.1 ± 0.1 mL/minute/kg (Cass 2011)

Time to Peak

IV: At the end of or just after infusion (Cass 2011)

Half-Life Elimination

3 to 4 hours (Cass 2011)

Protein Binding

~20%

Special Populations: Renal Function Impairment

AUC is increased and clearance is decreased in renal impairment.

Special Populations Note

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).

Use: Labeled Indications

Urinary tract infection, complicated (including pyelonephritis): 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.

Contraindications

Hypersensitivity to plazomicin, any aminoglycoside, or any component of the formulation

Dosing: Adult

Urinary tract infection (UTI), complicated: IV: 15 mg/kg once daily for 4 to 7 days; may follow with appropriate oral therapy to complete a total of 7 to 10 days of therapy (IV plus oral). Note: Use total body weight (TBW) to calculate dose in non-obese patients. For patients with TBW greater than ideal body weight (IBW) by ≥25%, see Dosing: Obesity.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Obesity

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).

Reconstitution

IV: Dilute in NS or LR to total volume of 50 mL (maximum concentration: 45 mg/mL).

Administration

IV: Infuse over 30 minutes.

Storage

Store intact vials refrigerated at 2°C to 8°C (36°F to 46°F). IV infusion solutions mixed in NS or LR at concentrations of 2.5 to 45 mg/mL are stable for 24 hours at room temperature or ≤7 days refrigerated.

Drug Interactions

Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Arbekacin: May enhance the nephrotoxic effect of Aminoglycosides. Arbekacin may enhance the ototoxic effect of Aminoglycosides. 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. Avoid combination

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Monitor therapy

Botulinum Toxin-Containing Products: Aminoglycosides may enhance the neuromuscular-blocking effect of Botulinum Toxin-Containing Products. Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Monitor therapy

CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Monitor therapy

Cephalosporins: May enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. 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. Avoid combination

CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

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. Consider therapy modification

CycloSPORINE (Systemic): Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Monitor therapy

Distigmine: Aminoglycosides may diminish the therapeutic effect of Distigmine. Monitor therapy

Foscarnet: May enhance the nephrotoxic effect of Aminoglycosides. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Monitor therapy

Mannitol (Systemic): May enhance the nephrotoxic effect of Aminoglycosides. Avoid combination

Mecamylamine: Aminoglycosides may enhance the neuromuscular-blocking effect of Mecamylamine. Avoid combination

Methoxyflurane: Aminoglycosides may enhance the nephrotoxic effect of Methoxyflurane. Avoid combination

Neuromuscular-Blocking Agents: Aminoglycosides may enhance the therapeutic effect of Neuromuscular-Blocking Agents. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Monitor therapy

Oxatomide: May enhance the ototoxic effect of Aminoglycosides. Monitor therapy

Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Monitor therapy

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. Consider therapy modification

Tenofovir Products: Aminoglycosides may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Adverse Reactions

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

ALERT: U.S. Boxed Warning

Nephrotoxicity:

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:

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.

Neuromuscular blockade:

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.

Pregnancy:

Aminoglycosides, including plazomicin, can cause fetal harm when administered to a pregnant woman.

Warnings/Precautions

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 (formerly Clostridium) 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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pregnancy: [US Boxed Warning]: Aminoglycosides may cause fetal harm if administered to a pregnant woman.

Monitoring Parameters

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

Pregnancy Considerations

[US Boxed Warning]: Aminoglycosides may cause fetal harm if administered to a pregnant woman.

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.

Patient Education

What is this drug used for?

• It is used to treat a urinary tract infection (UTI).

• It may be given to you for other reasons. Talk with the doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• Hearing loss

• Noise or ringing in the ears

• Severe dizziness

• Change in balance

• Muscle weakness

Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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