plazomicin (Rx)

Brand and Other Names:Zemdri
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

injection, single-dose vial

  • 500mg/10mL (50mg/mL)
  • Each vial contains plazomicin sulfate equivalent to 500 mg plazomicin free base

Complicated Urinary Tract Infections

Indicated for complicated urinary tract infections (cUTIs), including pyelonephritis caused by the following susceptible microorganism(s): Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae

Limited clinical safety and efficacy data are currently available, reserve treatment for use in cUTI patients who have limited or no alternative treatment options

15 mg/kg IV q24hr infused over 30 minutes

Duration of therapy should be guided by the severity of infection and the patient’s clinical status for up to 7 days; usual duration 4-7 days

An appropriate oral therapy may be considered after 4-7 days of therapy to complete a total duration of 7-10 days (IV plus oral); maximum duration of therapy for cUTI is 7 days

Also see Dosage Modifications and Administration

Sepsis

Pending FDA approval for acute bloodstream infections caused by multi-drug resistant Enterobacteriaceae infections, including carbapenem-resistant Enterobacteriaceae

Dosage Modifications

Renal impairment

  • CrCl ≥60 to 90 mL/min: 15 mg/kg IV q24hr
  • CrCl ≥30 to 60 mL/min: 10 mg/kg IV q24hr
  • CrCl ≥15 to 30 mL/min: 10 mg/kg IV q48hr
  • CrCl <15 mL/min, hemodialysis, or continuous renal replacement: Insufficient information

Hepatic impairment

  • Pharmacokinetics of plazomicin are unknown

Dosing Considerations

To reduce the development of drug-resistant bacteria and maintain the effectiveness of pIazomicin and other antibacterial drugs, use only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria

When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy; local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy when such data are unavailable

Monitoring

  • Assess CrCl in all patients prior to initiating therapy and daily during therapy
  • CrCl≥15 to <90 mL/min: Maintain plasma trough concentrations <3 mcg/mL; measure trough levels ~30 minutes before administration of the second dose of plazomicin
  • Estimate CrCl by the Cockcroft-Gault formula using total body weight (TBW) for patients with TBW greater than ideal body weight (IBW) by 25% or more, use IBW
  • Calculate dosage using TBW; for patients with TBW greater than IBW by 25% or more, use adjusted body weight based on the equation (Adjusted body weight = IBW + 0.4 × [TBW – IBW])
  • Dosage adjustment based on therapeutic drug monitoring (TDM) involves extending dosing interval by 1.5 fold (ie, from q24hr to q36 hr or from q48hr to q72 hr) for patients with plasma trough concentrations ≥3 mcg/mL
  • In the setting of worsening renal function, assess the benefit of continuing therapy

<18 years: Safety and efficacy not established

Plazomicin is substantially excreted by the kidneys, and the risk of adverse reactions to plazomicin may be greater in patients with renal impairment

Because elderly patients are more likely to have decreased renal function, monitor renal function

Dosage adjustment in elderly patients should take into account renal function and plazomicin concentrations as appropriate

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Adverse Effects

1-10%

Decreased renal function (3.6%)

Diarrhea (2.3%)

Hypertension (2.3%)

Treatment-associated ototoxicity (2.2%)

Headache (1.3%)

Nausea (1.3%)

Vomiting (1.3%)

Hypotension (1%)

Frequency Not Defined

Gastrointestinal disorders: Constipation, gastritis

Laboratory investigations: Alanine aminotransferase increased

Metabolism and nutrition disorders: Hypokalemia

Nervous system disorders: Dizziness

Renal and urinary disorders: Hematuria

Respiratory, thoracic, and mediastinal disorders: Dyspnea

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Warnings

Black Box Warnings

Nephrotoxicity

  • Nephrotoxicity reported; risk of nephrotoxicity is greater in patients with impaired renal function, elderly patients, and those receiving concomitant nephrotoxic medication
  • Assess CrCl in all patients prior to initiating therapy and daily during therapy
  • TDM is recommended for cUTI patients with CrCl <90 mL/min to avoid potentially toxic levels
  • See Dosage Modifications and Dosing Considerations

Ototoxicity

  • Ototoxicity, manifested as hearing loss, tinnitus, and/or vertigo, has been reported
  • Symptoms of aminoglycoside-associated ototoxicity may be irreversible and may not become evident until after completion of therapy
  • Aminoglycoside-associated ototoxicity observed primarily in patients with a family history of hearing loss, patients with renal impairment, and patients receiving higher doses and/or longer durations of therapy than recommended
  • Benefit-risk of therapy should be considered in patients with symptoms of ototoxicity

Neuromuscular blockade

  • Aminoglycosides have been associated with neuromuscular blockade
  • During therapy, monitor for adverse reactions associated with neuromuscular blockade, particularly in high-risk patients (eg, 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
  • See Pregnancy

Contraindications

Patients with known hypersensitivity to any aminoglycoside

Cautions

Also see Black Box Warnings

Nephrotoxicity reported; most serum creatinine increases were ≥1 mg/dL above baseline and reversible

Ototoxicity may occur

Aminoglycosides have been associated with exacerbation of muscle weakness in patients with underlying neuromuscular disorders, or delayed recovery of neuromuscular function in patients receiving concomitant neuromuscular blocking agents

Fetal harm may occur when administered to a pregnant woman (see Pregnancy)

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions reported in patients receiving aminoglycoside antibacterial drugs; discontinue treatment if an allergic reaction occurs

Prescribing a drug in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria

Clostridium difficile-associated diarrhea

  • Clostridium difficile-associated diarrhea (CDAD) reported for nearly all systemic antibacterial drugs and may range in severity from mild diarrhea to fatal colitis
  • Treatment with antibacterial drugs alters the normal flora of the colon and may permit overgrowth of C difficile; careful medical history is necessary
  • If CDAD is suspected or confirmed, antibacterial drugs not directed against C difficile may need to be discontinued
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Pregnancy

Pregnancy

Fetal harm may occur when administered to a pregnant woman

There are no available data on this drug in pregnant women to inform a drug-associated risk of adverse developmental outcomes

Animal data

  • Published literature reports of streptomycin, an aminoglycoside, state that it can cause total, irreversible, bilateral congenital deafness in children whose mothers received streptomycin during pregnancy
  • No drug-related visceral or skeletal malformations were observed in pregnant rats and rabbits administered subcutaneous plazomicin during organogenesis at maternal exposures ~0.8-fold (rats) and 2.5-fold (rabbits) of the human AUC at the clinical dose of 15 mg/kg/day
  • Auditory function of offspring was not measured in animal studies
  • Advise pregnant women of the potential risk to a fetus

Lactation

There are no data on the presence of plazomicin in human milk, the effects on the breastfed infant, or the effects on milk production

Plazomicin was detected in rat milk

Consider developmental and health benefits of breastfeeding along with the mother's clinical need for plazomicin and any potential adverse effects on the breastfed infant from plazomicin or from the underlying maternal condition

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

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Pharmacology

Mechanism of Action

Plazomicin sulfate is a semisynthetic aminoglycoside antibacterial derived from sisomicin

Engineered to overcome aminoglycoside-modifying enzymes (AMEs), the most common aminoglycoside-resistance mechanism in Enterobacteriaceae, and has in vitro activity against extended-spectrum beta-lactamase-producing, aminoglycoside-resistant, and carbapenem-resistant isolates

Absorption

AUC: 257 mcg·hr/mL (healthy subjects); 226 mcg·hr/mL (cUTI patients)

Peak plasma concentration: 73.7 mcg/mL (healthy subjects); 51 mcg/mL (cUTI patients)

Distribution

Protein bound: 20%

Vd: 17.9 L (healthy subjects); 30.8 L (cUTI patients)

Metabolism

Does not appear to be metabolized to any appreciable extent

Elimination

Clearance: 4.5 L/hr (healthy subjects); 5.1 L/hr (cUTIs)

Half-life: 3.5 hr (healthy subjects)

Excretion

  • Primarily excreted by the kidneys
  • Excretion following a single 15-mg/kg IV dose: Urine, within 4 hr (56%); urine, within 168 hr (89.1%); feces (<0.2%)
  • In total, 97.5% of the dose was recovered in the urine as unchanged plazomicin
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Administration

IV Compatibilities

0.9% NaCl or lactated Ringer injection

IV Incompatibilities

Compatibility of plazomicin for administration with other drugs has not been established

Do not mix with other drugs or physically add to solutions containing other drugs

Do infuse other medications simultaneously with plazomicin through the same IV line

IV Preparation

Dilute appropriate volume of plazomicin in 0.9% NaCl or lactated Ringer solution to achieve a final volume of 50 mL for IV infusion (final concentration: 2.5-45 mg/mL)

Vials do not contain preservatives

Follow appropriate aseptic technique in preparing the infusion solution

Discard unused portion vial

Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit

IV Administration

Infuse over 30 minutes

Storage

Unused vials: Refrigerate at 2-8°C (36-46°F)

Diluted solutions: Stable at room temperature for 24 hr

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Formulary

FormularyPatient Discounts

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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.