Dosing & Uses
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
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
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
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
Ototoxicity
- Cases of ototoxicity with antimicrobials#aminoglycosides have reported in patients with certain variants in mitochondrially encoded 12S rRNA gene (MT-RNR1), particularly the m.1555A>G variant; ototoxicity reported in some patients even when their aminoglycoside serum levels were within recommended range
- In case of known maternal history of ototoxicity due to aminoglycoside use or a known mitochondrial DNA variant in the patient, consider alternative treatments other than antimicrobials#aminoglycosides unless the increased risk of permanent hearing loss is outweighed by severity of infection and lack of safe and effective alternative therapies
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
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.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
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
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Zemdri intravenous - | 50 mg/mL vial |  | |
| Zemdri intravenous - | 50 mg/mL vial |  |
Copyright © 2010 First DataBank, Inc.
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