Contepo
Generic: FOSFOMYCIN DISODIUM
Basic Information
Manufacturer
Meitheal Pharmaceuticals Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
855574f2-39f8-43bc-a3d2-79dbb578cb94
Indications & Usage
1 INDICATIONS AND USAGE CONTEPO is an epoxide antibacterial indicated for the treatment of patients 18 years of age and older with complicated urinary tract infections (cUTI) including acute pyelonephritis caused by susceptible isolates of Escherichia coli and Klebsiella pneumoniae .
( 1.1 ) Usage to Reduce Development of Drug-Resistant Bacteria To reduce the development of drug-resistant bacteria and maintain the effectiveness of CONTEPO and other antibacterial drugs, CONTEPO should be used only to treat infections that are proven or strongly suspected to be caused by bacteria.
( 1.2 ) 1.1 Complicated Urinary Tract Infections (cUTI), including Acute Pyelonephritis CONTEPO is indicated for the treatment of patients 18 years and older with complicated urinary tract infections (cUTI), including acute pyelonephritis, caused by susceptible isolates of Escherichia coli and Klebsiella pneumoniae .
1.2 Usage to Reduce Development of Drug-Resistant Bacteria To reduce the development of drug-resistant bacteria and maintain the effectiveness of CONTEPO and other antibacterial drugs, CONTEPO should be used only to treat 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.
( 1.1 ) Usage to Reduce Development of Drug-Resistant Bacteria To reduce the development of drug-resistant bacteria and maintain the effectiveness of CONTEPO and other antibacterial drugs, CONTEPO should be used only to treat infections that are proven or strongly suspected to be caused by bacteria.
( 1.2 ) 1.1 Complicated Urinary Tract Infections (cUTI), including Acute Pyelonephritis CONTEPO is indicated for the treatment of patients 18 years and older with complicated urinary tract infections (cUTI), including acute pyelonephritis, caused by susceptible isolates of Escherichia coli and Klebsiella pneumoniae .
1.2 Usage to Reduce Development of Drug-Resistant Bacteria To reduce the development of drug-resistant bacteria and maintain the effectiveness of CONTEPO and other antibacterial drugs, CONTEPO should be used only to treat 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 adverse reactions are discussed in greater detail in the Warnings and Precautions section: Serum Electrolyte Abnormalities [see Warnings and Precautions ( 5.1 )] QT Prolongation [see Warnings and Precautions ( 5.2 )] Increased Transaminase Levels [see Warnings and Precautions ( 5.3 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.4 )] Neutropenia Including Agranulocytosis [see Warnings and Precautions ( 5.5 )] Clostridioides difficile -Associated Diarrhea [see Warnings and Precautions ( 5.6 )] Development of Drug-Resistant Bacteria [see Warnings and Precautions ( 5.7 )] Most common adverse reactions (incidence ≥2%) are transaminase elevations, hypokalemia, neutropenia, nausea, vomiting, diarrhea, hypocalcemia, hypernatremia, headache, and hypophosphatemia.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Meitheal Pharmaceuticals Inc.
at 1-844-824-8426 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.
CONTEPO was evaluated in a comparator-controlled clinical trial (Trial 1) in patients with cUTI, including acute pyelonephritis, which included 233 patients treated with CONTEPO and 231 treated with comparator (piperacillin/tazobactam 4.5 g every 8 hours) for 7 days, allowing bacteremic patients to receive up to 14 days.
No switch to oral antibacterial drugs was allowed.
The median age of treated patients was 54 years (range 18-89 years) and 64% were female.
All patients were white (100%).
Patients (99%) were predominantly enrolled in Eastern Europe.
Concomitant bacteremia was identified in 9% of patients at baseline.
Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation Serious adverse reactions occurred in 2.1% (5/233) CONTEPO and 2.6% (6/231) piperacillin/tazobactam-treated patients, respectively.
Treatment was discontinued due to adverse reactions in 3% (7/233) of patients receiving CONTEPO and in 2.6% (7/231) of patients receiving piperacillin/tazobactam.
The most common adverse reactions resulting in discontinuation of CONTEPO were gastrointestinal disorders (nausea, vomiting, and abdominal pain) in 1.3% (3/233) of patients.
No deaths occurred in the clinical trial.
Common Adverse Reactions Table 3 lists adverse reactions occurring in 2% or greater of patients receiving CONTEPO in Trial 1.
These adverse reactions were reversible upon completion of therapy.
Table 3 Adverse Reactions Occurring in 2% or Greater of Patients with cUTI Receiving CONTEPO in Trial 1 a Transaminase elevations include increased ALT and AST ≥3x ULN.
b Neutropenia includes absolute neutrophil count <1500 cells/mm 3 Adverse Reaction CONTEPO N=233 % Piperacillin/Tazobactam N=231 % Gastrointestinal Disorders Nausea 4.3 1.3 Diarrhea 3.9 4.8 Vomiting 3.9 0.4 Laboratory Investigations Transaminase elevations a 10.3 4.8 Hypokalemia 9.9 1.7 Hypophosphatemia 2.1 0.0 Hypocalcemia 3.9 2.6 Hypernatremia 3.4 0.9 Blood and Lymphatic System Disorders Neutropenia b 6.4 3.9 Nervous System Disorders Headache 2.6 2.2 Adverse Reactions Occurring in < 2% of Patients Receiving CONTEPO in Trial 1: Blood and lymphatic system disorders : anemia, thrombocytopenia Cardiac disorders : atrial fibrillation, palpitations, tachycardia, heart failure Ear and labyrinth disorders : hearing loss Gastrointestinal disorders : constipation General disorders and administration site conditions : asthenia, infusion site reactions, peripheral edema Hepatobiliary disorders : hepatic steatosis, hepatomegaly Infections and infestations : vaginal infection, vaginitis Investigations : increase creatinine kinase Metabolism and nutritional disorders : hyperglycemia Nervous system disorders : dysgeusia, syncope Respiratory, thoracic, and mediastinal disorders : dyspnea Skin and subcutaneous disorders : urticaria, rash, pruritis 6.2 Postmarketing Experience The following additional adverse reactions were not reported with CONTEPO-treated patients in Trial 1 but have been identified with the use of oral fosfomycin tromethamine or during use of intravenous fosfomycin sodium outside of the United States for various indications and dosing regimens.
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 : aplastic anemia, eosinophilia, agranulocytosis, leukopenia, pancytopenia Cardiac disorders: torsade de pointes Ear and labyrinth disorders : vertigo Eye disorders : visual impairment Gastrointestinal disorders : dyspepsia, C.
difficile -associated diarrhea and colitis, toxic megacolon Hepatobiliary disorders : alkaline phosphatase increased, cholestatic hepatitis, icterus, hepatic necrosis Immune system disorders : anaphylaxis Metabolism and nutrition disorders : decreased appetite Nervous system disorders : cerebral edema, dizziness, optic neuritis Psychiatric disorders : confusion Respiratory, thoracic, and mediastinal disorders : asthma attack, pulmonary edema Skin and subcutaneous tissue disorders : angioedema, facial edema Vascular disorders : hypertension
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Meitheal Pharmaceuticals Inc.
at 1-844-824-8426 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.
CONTEPO was evaluated in a comparator-controlled clinical trial (Trial 1) in patients with cUTI, including acute pyelonephritis, which included 233 patients treated with CONTEPO and 231 treated with comparator (piperacillin/tazobactam 4.5 g every 8 hours) for 7 days, allowing bacteremic patients to receive up to 14 days.
No switch to oral antibacterial drugs was allowed.
The median age of treated patients was 54 years (range 18-89 years) and 64% were female.
All patients were white (100%).
Patients (99%) were predominantly enrolled in Eastern Europe.
Concomitant bacteremia was identified in 9% of patients at baseline.
Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation Serious adverse reactions occurred in 2.1% (5/233) CONTEPO and 2.6% (6/231) piperacillin/tazobactam-treated patients, respectively.
Treatment was discontinued due to adverse reactions in 3% (7/233) of patients receiving CONTEPO and in 2.6% (7/231) of patients receiving piperacillin/tazobactam.
The most common adverse reactions resulting in discontinuation of CONTEPO were gastrointestinal disorders (nausea, vomiting, and abdominal pain) in 1.3% (3/233) of patients.
No deaths occurred in the clinical trial.
Common Adverse Reactions Table 3 lists adverse reactions occurring in 2% or greater of patients receiving CONTEPO in Trial 1.
These adverse reactions were reversible upon completion of therapy.
Table 3 Adverse Reactions Occurring in 2% or Greater of Patients with cUTI Receiving CONTEPO in Trial 1 a Transaminase elevations include increased ALT and AST ≥3x ULN.
b Neutropenia includes absolute neutrophil count <1500 cells/mm 3 Adverse Reaction CONTEPO N=233 % Piperacillin/Tazobactam N=231 % Gastrointestinal Disorders Nausea 4.3 1.3 Diarrhea 3.9 4.8 Vomiting 3.9 0.4 Laboratory Investigations Transaminase elevations a 10.3 4.8 Hypokalemia 9.9 1.7 Hypophosphatemia 2.1 0.0 Hypocalcemia 3.9 2.6 Hypernatremia 3.4 0.9 Blood and Lymphatic System Disorders Neutropenia b 6.4 3.9 Nervous System Disorders Headache 2.6 2.2 Adverse Reactions Occurring in < 2% of Patients Receiving CONTEPO in Trial 1: Blood and lymphatic system disorders : anemia, thrombocytopenia Cardiac disorders : atrial fibrillation, palpitations, tachycardia, heart failure Ear and labyrinth disorders : hearing loss Gastrointestinal disorders : constipation General disorders and administration site conditions : asthenia, infusion site reactions, peripheral edema Hepatobiliary disorders : hepatic steatosis, hepatomegaly Infections and infestations : vaginal infection, vaginitis Investigations : increase creatinine kinase Metabolism and nutritional disorders : hyperglycemia Nervous system disorders : dysgeusia, syncope Respiratory, thoracic, and mediastinal disorders : dyspnea Skin and subcutaneous disorders : urticaria, rash, pruritis 6.2 Postmarketing Experience The following additional adverse reactions were not reported with CONTEPO-treated patients in Trial 1 but have been identified with the use of oral fosfomycin tromethamine or during use of intravenous fosfomycin sodium outside of the United States for various indications and dosing regimens.
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 : aplastic anemia, eosinophilia, agranulocytosis, leukopenia, pancytopenia Cardiac disorders: torsade de pointes Ear and labyrinth disorders : vertigo Eye disorders : visual impairment Gastrointestinal disorders : dyspepsia, C.
difficile -associated diarrhea and colitis, toxic megacolon Hepatobiliary disorders : alkaline phosphatase increased, cholestatic hepatitis, icterus, hepatic necrosis Immune system disorders : anaphylaxis Metabolism and nutrition disorders : decreased appetite Nervous system disorders : cerebral edema, dizziness, optic neuritis Psychiatric disorders : confusion Respiratory, thoracic, and mediastinal disorders : asthma attack, pulmonary edema Skin and subcutaneous tissue disorders : angioedema, facial edema Vascular disorders : hypertension