Plazomicin

ZEMDRI is an antibacterial drug [see Microbiology (12.4) ] .

• 1. INDICATIONS AND USAGE ZEMDRI is an aminoglycoside antibacterial indicated for the treatment of patients 18 years of age or older with Complicated Urinary Tract Infections (cUTI) including Pyelonephritis.ICD-10: N39.0

• 4. CONTRAINDICATIONS ZEMDRI is contraindicated in patients with known hypersensitivity to any aminoglycoside [see Warnings and Precautions (5.5) ] .contraindicated

2. DOSAGE AND ADMINISTRATION Administer ZEMDRI 15 mg/kg every 24 hours by intravenous (IV) infusion over 30 minutes to patients 18 years of age or older with creatinine clearance greater than or equal to 90 mL/min. ( 2.1 ) Recommended duration of treatment is 4 to 7 days for cUTI, including pyelonephritis. ( 2.1 ) Assess creatinine clearance in all patients prior to initiating therapy and daily during therapy. ( 2.2 ) Recommended initial dosage regimen for patients with renal impairment is shown in the table below. ( 2.3 ) Estimated CLcr CLcr estimated by the Cockcroft-Gault formula. ( 2.3 ) (mL/min) Recommended Dosage for ZEMDRI Calculate dosage using Total Body Weight (TBW). For patients with TBW greater than IBW by 25% or more, use adjusted body weight. ( 2.3 ) Dosing Interval Greater than or equal to 60 to less than 90 15 mg/kg Every 24 hours Greater than or equal to 30 to less than 60 10 mg/kg Every 24 hours Greater than or equal to 15 to less than 30 10 mg/kg Every 48 hours See Full Prescribing Information for subsequent dosage adjustment based on changes in renal function or Therapeutic Drug Monitoring (TDM). ( 2.3 , 2.4 ). See Full Prescribing Information for instructions on preparation of the solution, stability in intravenous fluids and drug compatibilities. ( 2.5 , 2.6 , 2.7 ) 2.1 Recommended Dosage The recommended dosage regimen of ZEMDRI is 15 mg/kg administered every 24 hours by intravenous (IV) infusion over 30 minutes in patients 18 years of age or older and with creatinine clearance (CLcr) greater than or equal to 90 mL/min (Table 1).

5. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions, including anaphylaxis: Reported for aminoglycosides. If an allergic reaction occurs, discontinue ZEMDRI. ( 5.4 ) Clostridium difficile -Associated Diarrhea : Reported for nearly all systemic antibacterial drugs. Evaluate if diarrhea occurs. ( 5.5 ) 5.1 Nephrotoxicity Nephrotoxicity has been reported with the use of ZEMDRI [see Adverse Reactions (6.1) ]. Most serum creatinine increases were ≤ 1 mg/dL above baseline and reversible. In Trial 1, the incidence of adverse reactions associated with renal function (acute kidney injury, serum creatinine increased, chronic kidney disease, creatinine clearance decreased, renal failure, renal impairment) was 3.6% (11/303) in ZEMDRI-treated patients compared with 1.3% (4/301) in meropenem-treated patients [see Adverse Reactions (6.1) ]. Serum creatinine increases of 0.5 mg/dL or greater above baseline occurred in 7% (21/300) of ZEMDRI-treated patients compared with 4% (12/297) of meropenem-treated patients. These increases mainly occurred in patients with CLcr ≤ 90 mL/min and were associated with a plazomicin trough level (C min ) greater than or equal to 3 mcg/mL [see Adverse Reactions (6.1) and Clinical Pharmacology (12.2) ] . Assess CLcr in all patients prior to initiating therapy and daily during therapy with ZEMDRI, particularly in those at increased risk of nephrotoxicity, such as those with renal impairment, the elderly, and those receiving concomitant potentially nephrotoxic medications.

6. ADVERSE REACTIONS The following important adverse reactions are discussed in greater detail in the Warnings and Precautions section: Nephrotoxicity [see Warnings and Precautions (5.1) ] Ototoxicity [see Warnings and Precautions (5.2) ] Neuromuscular Blockade [see Warnings and Precautions (5.3) ] Fetal Harm [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Clostridium difficile -Associated Diarrhea [see Warnings and Precautions (5.6) ] Most common adverse reactions (≥ 1% of patients treated with ZEMDRI) are decreased renal function, diarrhea, hypertension, headache, nausea, vomiting and hypotension. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Achaogen at 1-833-252-6402 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be compared directly to rates in the clinical trials of another drug and may not reflect the rates observed in practice. ZEMDRI was evaluated in two comparator-controlled clinical trials (Trial 1, NCT02486627 and Trial 2, NCT01096849) in patients with cUTI, including pyelonephritis. In both trials, patients with CLcr greater than 60 mL/min received ZEMDRI 15 mg/kg IV once daily as a 30-minute infusion [ see Clinical Studies (14.1) ] . Trial 1 included 303 patients treated with ZEMDRI and 301 patients treated with meropenem. Patients were to receive 4 to 7 days of ZEMDRI (mean duration of 5.1 days).

8. USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Aminoglycosides, including ZEMDRI, can cause fetal harm when administered to a pregnant woman. There are no available data on the use of ZEMDRI in pregnant women to inform a drug associated risk of adverse developmental outcomes. 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 approximately 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 (see Data ) . Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Metabolism

The pharmacokinetic (PK) parameters of plazomicin are similar for single- and multiple-dose administration of ZEMDRI in healthy subjects. No appreciable accumulation of plazomicin was observed following multiple IV infusions of 15 mg/kg administered every 24 hours in subjects with normal renal function.

10. OVERDOSAGE In the event of overdosage, ZEMDRI should be discontinued and supportive care is advised. Maintenance of glomerular filtration and careful monitoring of renal function is recommended. Hemodialysis may aid in the removal of ZEMDRI from the blood, especially if renal function is, or becomes, compromised. No clinical information is available on the use of hemodialysis to treat ZEMDRI overdosage.

• Jun 25, 2018NDANDA210303Cipla Usa

1. 1Acute Kidney Injury133%
2. 2Antibiotic Level Above Therapeutic133%
3. 3Creatinine Renal Clearance Decreased133%
4. 4Drug Effect Less Than Expected133%
5. 5Gastrointestinal Haemorrhage133%
6. 6Renal Failure133%

The 10 most recently updated of 10 ClinicalTrials.gov registrations naming Plazomicin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Plazomicin Study in ESRD Patients Receiving IHD
  Completed · Phase 1 · Interventional · 6 enrolled · Cipla USA Inc.
  NCT04699656updated 2022-03-09
• A Study of Plazomicin Compared With Colistin in Patients With Infection Due to Carbapenem-Resistant Enterobacteriaceae (CRE)
  Completed · Phase 3 · Interventional · 69 enrolled · Achaogen, Inc.
  NCT01970371updated 2018-10-16
• A Study of Plazomicin Compared With Meropenem for the Treatment of Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis (AP)
  Completed · Phase 3 · Interventional · 609 enrolled · Achaogen, Inc.
  NCT02486627updated 2018-08-23
• A Study of Plazomicin Compared With Levofloxacin for the Treatment of Complicated Urinary Tract Infection (cUTI) and Acute Pyelonephritis (AP)
  Completed · Phase 2 · Interventional · 145 enrolled · Achaogen, Inc.
  NCT01096849updated 2018-08-22
• A Study to Assess the Effect of Plazomicin on the Pharmacokinetics of Metformin
  Completed · Phase 1 · Interventional · 16 enrolled · Achaogen, Inc.
  NCT03270553updated 2017-10-11
• A Study to Assess the Metabolism, Excretion, and Mass Balance of Radio-Labeled Plazomicin
  Completed · Phase 1 · Interventional · 6 enrolled · Achaogen, Inc.
  NCT03177278updated 2017-07-12
• PK Study of ACHN-490 Injection in Renally Impaired Subjects
  Completed · Phase 1 · Interventional · 24 enrolled · Achaogen, Inc.
  NCT01462136updated 2012-08-23
• A Study to Evaluate the Effect of IV ACHN-490 Injection on the QT/QTc Interval in Healthy Volunteers
  Completed · Phase 1 · Interventional · 64 enrolled · Achaogen, Inc.
  NCT01514929updated 2012-05-09
• Phase 1 Study for Safety of ACHN-490
  Completed · Phase 1 · Interventional · 39 enrolled · Achaogen, Inc.
  NCT00822978updated 2012-02-27
• Phase 1 Study to Determine Safety, Blood PK and Lung Penetration
  Completed · Phase 1 · Interventional · 40 enrolled · Achaogen, Inc.
  NCT01034774updated 2012-02-27

CPIC-curated drug–gene pairs for Plazomicin. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• MT-RNR1CPIC AFDA label: Actionable PGx
  MT-RNR1 and Aminoglycosides

Frequently asked questions

How does Plazomicin work?

ZEMDRI is an antibacterial drug [see Microbiology (12.4) ] .

What is Plazomicin used for?

According to FDA labeling, Plazomicin carries indications including: 1. INDICATIONS AND USAGE ZEMDRI is an aminoglycoside antibacterial indicated for the treatment of patients 18 years of age or older with Complicated Urinary Tract Infections (cUTI) including Pyelonephritis.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Plazomicin?

Plazomicin is classified as Other aminoglycosides, Protein Synthesis Inhibitors, Decreased Protein Synthesis.

What are the brand names for Plazomicin?

Plazomicin is marketed under brand names including Zemdri.

What are the contraindications for Plazomicin?

Plazomicin labeling lists contraindications including: 4. CONTRAINDICATIONS ZEMDRI is contraindicated in patients with known hypersensitivity to any aminoglycoside [see Warnings and Precautions (5.5) ] .. Always consult the full prescribing information and a clinician.