Fetroja
Generic: CEFIDEROCOL SULFATE TOSYLATE
Basic Information
Manufacturer
Shionogi Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
75c0c785-38e0-4049-a6fb-b77581f5b35c
Indications & Usage
1 INDICATIONS AND USAGE FETROJA is a cephalosporin antibacterial indicated in patients 18 years of age or older for the treatment of the following infections caused by susceptible Gram-negative microorganisms: Complicated Urinary Tract Infections (cUTI), including Pyelonephritis ( 1.1 ) Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) ( 1.2 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of FETROJA and other antibacterial drugs, FETROJA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
( 1.3 ) 1.1 Complicated Urinary Tract Infections (cUTIs), Including Pyelonephritis FETROJA ® is indicated in patients 18 years of age or older for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis caused by the following susceptible Gram-negative microorganisms: Escherichia coli , Klebsiella pneumoniae , Proteus mirabilis , Pseudomonas aeruginosa , and Enterobacter cloacae complex [see Clinical Studies (14.1) ] .
1.2 Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) FETROJA is indicated in patients 18 years of age or older for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia, caused by the following susceptible Gram-negative microorganisms: Acinetobacter baumannii complex, Escherichia coli , Enterobacter cloacae complex, Klebsiella pneumoniae , Pseudomonas aeruginosa , and Serratia marcescens [see Clinical Studies (14.2) ].
1.3 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of FETROJA and other antibacterial drugs, FETROJA 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.
( 1.3 ) 1.1 Complicated Urinary Tract Infections (cUTIs), Including Pyelonephritis FETROJA ® is indicated in patients 18 years of age or older for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis caused by the following susceptible Gram-negative microorganisms: Escherichia coli , Klebsiella pneumoniae , Proteus mirabilis , Pseudomonas aeruginosa , and Enterobacter cloacae complex [see Clinical Studies (14.1) ] .
1.2 Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) FETROJA is indicated in patients 18 years of age or older for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia, caused by the following susceptible Gram-negative microorganisms: Acinetobacter baumannii complex, Escherichia coli , Enterobacter cloacae complex, Klebsiella pneumoniae , Pseudomonas aeruginosa , and Serratia marcescens [see Clinical Studies (14.2) ].
1.3 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of FETROJA and other antibacterial drugs, FETROJA 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 serious adverse reactions are described in greater detail in the Warnings and Precautions section: Increase in All-Cause Mortality in Patients with Carbapenem-Resistant Gram-Negative Bacterial Infections [see Warnings and Precautions (5.1) ] Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] Clostridioides difficile -associated Diarrhea (CDAD) [see Warnings and Precautions (5.3) ] Seizures and Other Central Nervous System Adverse Reactions [see Warnings and Precautions (5.4) ] cUTI: The most frequently occurring adverse reactions in greater than or equal to 2% of cUTI patients treated with FETROJA were diarrhea, infusion site reactions, constipation, rash, candidiasis, cough, elevations in liver tests, headache, hypokalemia, nausea, and vomiting.
( 6.1 ) HABP/VABP: The most frequently occurring adverse reactions in greater than or equal to 4% of HABP/VABP patients treated with FETROJA were elevations in liver tests, hypokalemia, diarrhea, hypomagnesemia, and atrial fibrillation.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Shionogi Inc.
at 1-800-849-9707 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Complicated Urinary Tract Infections (cUTIs), Including Pyelonephritis FETROJA was evaluated in an active-controlled, randomized clinical trial in patients with cUTI, including pyelonephritis (Trial 1).
In this trial, 300 patients received FETROJA 2 grams every 8 hours infused over 1 hour (or a renally-adjusted dose), and 148 patients were treated with imipenem/cilastatin 1gram/1gram every 8 hours infused over 1 hour (or a renally-adjusted dose).
The median age of treated patients across treatment arms was 65 years (range 18 to 93 years), with approximately 53% of patients aged greater than or equal to 65.
Approximately 96% of patients were White, most were from Europe, and 55% were female.
Patients across treatment arms received treatment for a median duration of 9 days.
Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation In Trial 1, a total of 14/300 (4.7%) cUTI patients treated with FETROJA and 12/148 (8.1%) of cUTI patients treated with imipenem/cilastatin experienced serious adverse reactions.
One death (0.3%) occurred in 300 patients treated with FETROJA as compared to none treated with imipenem/cilastatin.
Discontinuation of treatment due to any adverse reaction occurred in 5/300 (1.7%) of patients treated with FETROJA and 3/148 (2.0%) of patients treated with imipenem/cilastatin.
Specific adverse reactions leading to treatment discontinuation in patients who received FETROJA included diarrhea (0.3%), drug hypersensitivity (0.3%), and increased hepatic enzymes (0.3%).
Common Adverse Reactions Table 4 lists the most common selected adverse reactions occurring in ≥ 2% of cUTI patients receiving FETROJA in Trial 1.
Table 4 Selected Adverse Reactions Occurring in ≥ 2% of cUTI Patients Receiving FETROJA in Trial 1 Adverse Reaction FETROJA 2 grams IV over 1 hour every 8 hours (with dosing adjustment based on renal function).
(N = 300) Imipenem/Cilastatin 1 gram IV over 1 hour every 8 hours (with dosing adjustment based on renal function and body weight).
(N = 148) cUTI = complicated urinary tract infection.
Diarrhea 4% 6% Infusion site reactions Infusion site reactions include infusion site erythema, inflammation, pain, pruritus, injection site pain, and phlebitis.
4% 5% Constipation 3% 4% Rash Rash includes rash macular, rash maculopapular, erythema, skin irritation.
3% < 1% Candidiasis Candidiasis includes oral or vulvovaginal candidiasis, candiduria.
2% 3% Cough 2% < 1% Elevations in liver tests Elevations in liver tests include alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, blood alkaline phosphatase, hepatic enzyme increased.
2% < 1% Headache 2% 5% Hypokalemia Hypokalemia includes blood potassium decreased.
2% 3% Nausea 2% 4% Vomiting 2% 1% Other Adverse Reactions of FETROJA in the cUTI Patients (Trial 1) The following selected adverse reactions were reported in FETROJA-treated cUTI patients at a rate of less than 2% in Trial 1: Blood and lymphatic disorders : thrombocytosis Cardiac disorders : congestive heart failure, bradycardia, atrial fibrillation Gastrointestinal disorders : abdominal pain, dry mouth, stomatitis General system disorders : pyrexia, peripheral edema Hepatobiliary disorders : cholelithiasis, cholecystitis, gallbladder pain Immune system disorders : drug hypersensitivity Infections and infestations : C.
difficile infection Laboratory investigations : prolonged prothrombin time (PT) and prothrombin time international normalized ratio (PT-INR), red blood cells urine positive, creatine phosphokinase increase Metabolism and nutrition disorders : decreased appetite, hypocalcemia, fluid overload Nervous system disorders : dysgeusia, seizure Respiratory, thoracic, and mediastinal disorders : dyspnea, pleural effusion Skin and subcutaneous tissue disorders : pruritus Psychiatric disorders : insomnia, restlessness Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) FETROJA was evaluated in an active-controlled clinical trial in patients with HABP/VABP (Trial 2).
In this trial, 148 patients received FETROJA 2 grams every 8 hours infused over 3 hours, and 150 patients received meropenem 2 grams every 8 hours infused over 3 hours.
Doses of study treatments were adjusted based on renal function.
The median age was 67 years, approximately 59% of patients were 65 years of age and older, 69% were male, and 68% were White.
Overall, approximately 60% were ventilated at randomization, including 41% with VABP and 14% with ventilated HABP.
The mean Acute Physiology And Chronic Health Evaluation (APACHE II) score was 16.
All patients received empiric treatment for Gram-positive organisms with linezolid for at least 5 days.
Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation In Trial 2, serious adverse reactions occurred in 54/148 (36.5%) HABP/VABP patients treated with FETROJA and 45/150 (30%) of HABP/VABP patients treated with meropenem.
Adverse reactions leading to death were reported in 39/148 (26.4%) patients treated with FETROJA and 35/150 (23.3%) patients treated with meropenem.
Adverse reactions leading to discontinuation of treatment occurred in 12/148 (8.1%) of patients treated with FETROJA and 14/150 (9.3%) of patients treated with meropenem.
The most common adverse reactions leading to discontinuation in both treatment groups were elevated liver tests.
Common Adverse Reactions Table 5 lists the most common selected adverse reactions occurring in ≥ 4% of patients receiving FETROJA in the HABP/VABP trial.
Table 5 Selected Adverse Reactions Occurring in ≥ 4% of HABP/VABP Patients Receiving FETROJA in Trial 2 Adverse Reaction FETROJA 2 grams IV over 3 hours every 8 hours (with dosing adjustment based on renal function).
N = 148 Meropenem 2 grams IV over 3 hours every 8 hours (with dosing adjustment based on renal function).
N = 150 HABP/VABP = hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia.
Elevations in liver tests Elevations in liver tests include the following terms: aspartate aminotransferase increased, alanine aminotransferase increased, gamma-glutamyl transferase increased, liver function test increased, liver function test abnormal, hepatic enzyme increased, transaminases increased, hypertransaminesemia.
16% 16% Hypokalemia Hypokalemia includes blood potassium decreased.
11% 15% Diarrhea 9% 9% Hypomagnesemia 5% < 1% Atrial fibrillation 5% 3% Other Adverse Reactions of FETROJA in HABP/VABP Patients in Trial 2 The following selected adverse reactions were reported in FETROJA-treated HABP/VABP patients at a rate of less than 4% in Trial 2: Blood and lymphatic disorders : thrombocytopenia, thrombocytosis Cardiac disorders : myocardial infarction, atrial flutter Gastrointestinal disorders : nausea, vomiting, abdominal pain Hepatobiliary disorders : cholecystitis, cholestasis Infections and infestations : C.
difficile infection, oral candidiasis Laboratory investigations : prolonged prothrombin time (PT) and prothrombin time international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT) Metabolism and nutrition disorders : hypocalcemia, hyperkalemia Nervous system disorders : seizure Renal and genitourinary disorders : acute interstitial nephritis Respiratory, thoracic, and mediastinal disorders : cough Skin and subcutaneous tissue disorders : rash including rash erythematous 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of FETROJA.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and lymphatic system disorders : neutropenia, eosinophilia Renal and urinary disorders : chromaturia
( 6.1 ) HABP/VABP: The most frequently occurring adverse reactions in greater than or equal to 4% of HABP/VABP patients treated with FETROJA were elevations in liver tests, hypokalemia, diarrhea, hypomagnesemia, and atrial fibrillation.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Shionogi Inc.
at 1-800-849-9707 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Complicated Urinary Tract Infections (cUTIs), Including Pyelonephritis FETROJA was evaluated in an active-controlled, randomized clinical trial in patients with cUTI, including pyelonephritis (Trial 1).
In this trial, 300 patients received FETROJA 2 grams every 8 hours infused over 1 hour (or a renally-adjusted dose), and 148 patients were treated with imipenem/cilastatin 1gram/1gram every 8 hours infused over 1 hour (or a renally-adjusted dose).
The median age of treated patients across treatment arms was 65 years (range 18 to 93 years), with approximately 53% of patients aged greater than or equal to 65.
Approximately 96% of patients were White, most were from Europe, and 55% were female.
Patients across treatment arms received treatment for a median duration of 9 days.
Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation In Trial 1, a total of 14/300 (4.7%) cUTI patients treated with FETROJA and 12/148 (8.1%) of cUTI patients treated with imipenem/cilastatin experienced serious adverse reactions.
One death (0.3%) occurred in 300 patients treated with FETROJA as compared to none treated with imipenem/cilastatin.
Discontinuation of treatment due to any adverse reaction occurred in 5/300 (1.7%) of patients treated with FETROJA and 3/148 (2.0%) of patients treated with imipenem/cilastatin.
Specific adverse reactions leading to treatment discontinuation in patients who received FETROJA included diarrhea (0.3%), drug hypersensitivity (0.3%), and increased hepatic enzymes (0.3%).
Common Adverse Reactions Table 4 lists the most common selected adverse reactions occurring in ≥ 2% of cUTI patients receiving FETROJA in Trial 1.
Table 4 Selected Adverse Reactions Occurring in ≥ 2% of cUTI Patients Receiving FETROJA in Trial 1 Adverse Reaction FETROJA 2 grams IV over 1 hour every 8 hours (with dosing adjustment based on renal function).
(N = 300) Imipenem/Cilastatin 1 gram IV over 1 hour every 8 hours (with dosing adjustment based on renal function and body weight).
(N = 148) cUTI = complicated urinary tract infection.
Diarrhea 4% 6% Infusion site reactions Infusion site reactions include infusion site erythema, inflammation, pain, pruritus, injection site pain, and phlebitis.
4% 5% Constipation 3% 4% Rash Rash includes rash macular, rash maculopapular, erythema, skin irritation.
3% < 1% Candidiasis Candidiasis includes oral or vulvovaginal candidiasis, candiduria.
2% 3% Cough 2% < 1% Elevations in liver tests Elevations in liver tests include alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, blood alkaline phosphatase, hepatic enzyme increased.
2% < 1% Headache 2% 5% Hypokalemia Hypokalemia includes blood potassium decreased.
2% 3% Nausea 2% 4% Vomiting 2% 1% Other Adverse Reactions of FETROJA in the cUTI Patients (Trial 1) The following selected adverse reactions were reported in FETROJA-treated cUTI patients at a rate of less than 2% in Trial 1: Blood and lymphatic disorders : thrombocytosis Cardiac disorders : congestive heart failure, bradycardia, atrial fibrillation Gastrointestinal disorders : abdominal pain, dry mouth, stomatitis General system disorders : pyrexia, peripheral edema Hepatobiliary disorders : cholelithiasis, cholecystitis, gallbladder pain Immune system disorders : drug hypersensitivity Infections and infestations : C.
difficile infection Laboratory investigations : prolonged prothrombin time (PT) and prothrombin time international normalized ratio (PT-INR), red blood cells urine positive, creatine phosphokinase increase Metabolism and nutrition disorders : decreased appetite, hypocalcemia, fluid overload Nervous system disorders : dysgeusia, seizure Respiratory, thoracic, and mediastinal disorders : dyspnea, pleural effusion Skin and subcutaneous tissue disorders : pruritus Psychiatric disorders : insomnia, restlessness Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) FETROJA was evaluated in an active-controlled clinical trial in patients with HABP/VABP (Trial 2).
In this trial, 148 patients received FETROJA 2 grams every 8 hours infused over 3 hours, and 150 patients received meropenem 2 grams every 8 hours infused over 3 hours.
Doses of study treatments were adjusted based on renal function.
The median age was 67 years, approximately 59% of patients were 65 years of age and older, 69% were male, and 68% were White.
Overall, approximately 60% were ventilated at randomization, including 41% with VABP and 14% with ventilated HABP.
The mean Acute Physiology And Chronic Health Evaluation (APACHE II) score was 16.
All patients received empiric treatment for Gram-positive organisms with linezolid for at least 5 days.
Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation In Trial 2, serious adverse reactions occurred in 54/148 (36.5%) HABP/VABP patients treated with FETROJA and 45/150 (30%) of HABP/VABP patients treated with meropenem.
Adverse reactions leading to death were reported in 39/148 (26.4%) patients treated with FETROJA and 35/150 (23.3%) patients treated with meropenem.
Adverse reactions leading to discontinuation of treatment occurred in 12/148 (8.1%) of patients treated with FETROJA and 14/150 (9.3%) of patients treated with meropenem.
The most common adverse reactions leading to discontinuation in both treatment groups were elevated liver tests.
Common Adverse Reactions Table 5 lists the most common selected adverse reactions occurring in ≥ 4% of patients receiving FETROJA in the HABP/VABP trial.
Table 5 Selected Adverse Reactions Occurring in ≥ 4% of HABP/VABP Patients Receiving FETROJA in Trial 2 Adverse Reaction FETROJA 2 grams IV over 3 hours every 8 hours (with dosing adjustment based on renal function).
N = 148 Meropenem 2 grams IV over 3 hours every 8 hours (with dosing adjustment based on renal function).
N = 150 HABP/VABP = hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia.
Elevations in liver tests Elevations in liver tests include the following terms: aspartate aminotransferase increased, alanine aminotransferase increased, gamma-glutamyl transferase increased, liver function test increased, liver function test abnormal, hepatic enzyme increased, transaminases increased, hypertransaminesemia.
16% 16% Hypokalemia Hypokalemia includes blood potassium decreased.
11% 15% Diarrhea 9% 9% Hypomagnesemia 5% < 1% Atrial fibrillation 5% 3% Other Adverse Reactions of FETROJA in HABP/VABP Patients in Trial 2 The following selected adverse reactions were reported in FETROJA-treated HABP/VABP patients at a rate of less than 4% in Trial 2: Blood and lymphatic disorders : thrombocytopenia, thrombocytosis Cardiac disorders : myocardial infarction, atrial flutter Gastrointestinal disorders : nausea, vomiting, abdominal pain Hepatobiliary disorders : cholecystitis, cholestasis Infections and infestations : C.
difficile infection, oral candidiasis Laboratory investigations : prolonged prothrombin time (PT) and prothrombin time international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT) Metabolism and nutrition disorders : hypocalcemia, hyperkalemia Nervous system disorders : seizure Renal and genitourinary disorders : acute interstitial nephritis Respiratory, thoracic, and mediastinal disorders : cough Skin and subcutaneous tissue disorders : rash including rash erythematous 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of FETROJA.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and lymphatic system disorders : neutropenia, eosinophilia Renal and urinary disorders : chromaturia