Zemdri (plazomicin)
Generic: PLAZOMICIN
Basic Information
Manufacturer
Achaogen, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
0b82ffed-27f4-4f5c-8135-670c148f0e12
Indications & Usage
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.
( 1.1 ) As only limited clinical safety and efficacy data are available, reserve ZEMDRI for use in patients who have limited or no alternative treatment options.
( 1.1 ) To reduce the development of drug-resistant bacteria and maintain effectiveness of ZEMDRI and other antibacterial drugs, ZEMDRI should be used only to treat infections that are proven or strongly suspected to be caused by susceptible microorganisms.
( 1.2 ) 1.1 Complicated Urinary Tract Infections (cUTI), including Pyelonephritis ZEMDRI is indicated in patients 18 years of age or older for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis caused by the following susceptible microorganism(s): Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis , and Enterobacter cloacae .
As only limited clinical safety and efficacy data for ZEMDRI are currently available, reserve ZEMDRI for use in cUTI patients who have limited or no alternative treatment options [see Clinical Studies (14.1) ].
1.2 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZEMDRI and other antibacterial drugs, ZEMDRI should be used 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.
In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
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.
( 1.1 ) As only limited clinical safety and efficacy data are available, reserve ZEMDRI for use in patients who have limited or no alternative treatment options.
( 1.1 ) To reduce the development of drug-resistant bacteria and maintain effectiveness of ZEMDRI and other antibacterial drugs, ZEMDRI should be used only to treat infections that are proven or strongly suspected to be caused by susceptible microorganisms.
( 1.2 ) 1.1 Complicated Urinary Tract Infections (cUTI), including Pyelonephritis ZEMDRI is indicated in patients 18 years of age or older for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis caused by the following susceptible microorganism(s): Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis , and Enterobacter cloacae .
As only limited clinical safety and efficacy data for ZEMDRI are currently available, reserve ZEMDRI for use in cUTI patients who have limited or no alternative treatment options [see Clinical Studies (14.1) ].
1.2 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZEMDRI and other antibacterial drugs, ZEMDRI should be used 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.
In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Adverse Reactions
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).
In some patients, parenteral therapy was followed by a switch to an oral antibacterial drug.
The median age of patients treated with ZEMDRI in Trial 1 was 62 years (range 18 to 90 years) and 45.2% of patients were 65 years of age or older.
Patients treated with ZEMDRI were predominantly female (56.1%) and White (99.3%).
A majority of patients (68.0%) had mild or moderate renal impairment (CLcr >30 to 90 mL/min) at baseline.
Patients with CLcr of 30 mL/min or less were excluded.
Adverse Reactions Leading to Treatment Discontinuations in Trial 1 In Trial 1, treatment discontinuation from IV study drug due to an adverse reaction occurred in 2.0% of patients receiving ZEMDRI (6/303) and meropenem (6/301), respectively.
Common Adverse Reactions in Trial 1 Table 3 lists adverse reactions occurring in 1% or more of patients receiving ZEMDRI in Trial 1.
Table 3: Incidence (%) of Adverse Reactions Occurring in 1% or More of cUTI Adult Patients Treated With ZEMDRI in Trial 1 Adverse Reactions ZEMDRI (N=303) n (%) Meropenem 1 g IV every 8 hours.
(N=301) n (%) Decreased Renal Function Combined term that corresponds to adverse reactions associated with renal function described in Nephrotoxicity section below.
11 (3.6) 4 (1.3) Diarrhea 7 (2.3) 5 (1.7) Hypertension 7 (2.3) 7 (2.3) Headache 4 (1.3) 9 (3.0) Nausea 4 (1.3) 4 (1.3) Vomiting 4 (1.3) 3 (1.0) Hypotension 3 (1.0) 2 (0.7) The adverse reactions profile for the cUTI patients in Trial 2 were similar to those observed in Trial 1.
Nephrotoxicity Reported in Trial 1 In Trial 1, serum creatinine increases of 0.5 mg/dL or greater above baseline occurred in 7.0% (21/300) of ZEMDRI-treated patients compared with 4.0% (12/297) of meropenem-treated patients.
Of these, the incidence during IV therapy was 3.7% (11/300) vs 3.0% (9/297) in ZEMDRI- and meropenem-treated patients, respectively.
By the last follow-up visit (between 8 to 43 days after completion of IV therapy), the majority of ZEMDRI-treated patients (9/11) and all meropenem treated patients (9/9) with serum creatinine increases while on therapy had fully recovered renal function.
Serum creatinine increases of 0.5 mg/dL or greater above baseline were observed following completion of IV therapy.
These increases were generally ≤ 1.0 mg/dL above baseline and recovered by the next measurement.
In cUTI patients with CLcr of greater than 30 and less than or equal to 90 mL/min, 9.7% (20/207) ZEMDRI-treated and 4.1% (9/217) meropenem-treated patients had serum creatinine increases of 0.5 mg/dL or greater above baseline.
In cUTI patients with CLcr greater than 90 mL/min, 1.1% (1/93) ZEMDRI-treated and 3.8% (3/80) of meropenem-treated patients had serum creatinine increases of 0.5 mg/dL or greater above baseline [see Use in Specific Populations (8.6) ] .
Ototoxicity Pure tone audiometry was evaluated in Phase 1 trials and in Trial 2.
Treatment associated ototoxicity could not be definitively excluded according to the American Speech-Language-Hearing Association criteria 1 in 2.2% (4/182) of ZEMDRI-exposed and 2.0% (1/49) of comparator- or placebo-exposed adults.
Other Adverse Reactions Reported with ZEMDRI The following selected adverse reactions were reported in more than one ZEMDRI-treated patient in Trials 1 and 2 and are not described elsewhere in the labeling: 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
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).
In some patients, parenteral therapy was followed by a switch to an oral antibacterial drug.
The median age of patients treated with ZEMDRI in Trial 1 was 62 years (range 18 to 90 years) and 45.2% of patients were 65 years of age or older.
Patients treated with ZEMDRI were predominantly female (56.1%) and White (99.3%).
A majority of patients (68.0%) had mild or moderate renal impairment (CLcr >30 to 90 mL/min) at baseline.
Patients with CLcr of 30 mL/min or less were excluded.
Adverse Reactions Leading to Treatment Discontinuations in Trial 1 In Trial 1, treatment discontinuation from IV study drug due to an adverse reaction occurred in 2.0% of patients receiving ZEMDRI (6/303) and meropenem (6/301), respectively.
Common Adverse Reactions in Trial 1 Table 3 lists adverse reactions occurring in 1% or more of patients receiving ZEMDRI in Trial 1.
Table 3: Incidence (%) of Adverse Reactions Occurring in 1% or More of cUTI Adult Patients Treated With ZEMDRI in Trial 1 Adverse Reactions ZEMDRI (N=303) n (%) Meropenem 1 g IV every 8 hours.
(N=301) n (%) Decreased Renal Function Combined term that corresponds to adverse reactions associated with renal function described in Nephrotoxicity section below.
11 (3.6) 4 (1.3) Diarrhea 7 (2.3) 5 (1.7) Hypertension 7 (2.3) 7 (2.3) Headache 4 (1.3) 9 (3.0) Nausea 4 (1.3) 4 (1.3) Vomiting 4 (1.3) 3 (1.0) Hypotension 3 (1.0) 2 (0.7) The adverse reactions profile for the cUTI patients in Trial 2 were similar to those observed in Trial 1.
Nephrotoxicity Reported in Trial 1 In Trial 1, serum creatinine increases of 0.5 mg/dL or greater above baseline occurred in 7.0% (21/300) of ZEMDRI-treated patients compared with 4.0% (12/297) of meropenem-treated patients.
Of these, the incidence during IV therapy was 3.7% (11/300) vs 3.0% (9/297) in ZEMDRI- and meropenem-treated patients, respectively.
By the last follow-up visit (between 8 to 43 days after completion of IV therapy), the majority of ZEMDRI-treated patients (9/11) and all meropenem treated patients (9/9) with serum creatinine increases while on therapy had fully recovered renal function.
Serum creatinine increases of 0.5 mg/dL or greater above baseline were observed following completion of IV therapy.
These increases were generally ≤ 1.0 mg/dL above baseline and recovered by the next measurement.
In cUTI patients with CLcr of greater than 30 and less than or equal to 90 mL/min, 9.7% (20/207) ZEMDRI-treated and 4.1% (9/217) meropenem-treated patients had serum creatinine increases of 0.5 mg/dL or greater above baseline.
In cUTI patients with CLcr greater than 90 mL/min, 1.1% (1/93) ZEMDRI-treated and 3.8% (3/80) of meropenem-treated patients had serum creatinine increases of 0.5 mg/dL or greater above baseline [see Use in Specific Populations (8.6) ] .
Ototoxicity Pure tone audiometry was evaluated in Phase 1 trials and in Trial 2.
Treatment associated ototoxicity could not be definitively excluded according to the American Speech-Language-Hearing Association criteria 1 in 2.2% (4/182) of ZEMDRI-exposed and 2.0% (1/49) of comparator- or placebo-exposed adults.
Other Adverse Reactions Reported with ZEMDRI The following selected adverse reactions were reported in more than one ZEMDRI-treated patient in Trials 1 and 2 and are not described elsewhere in the labeling: 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