Meropenem
Generic: MEROPENEM
Basic Information
Manufacturer
Eugia US LLC
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
bf1d3433-9e3f-40a0-8bff-c8ceaa8bab7c
Indications & Usage
1 INDICATIONS AND USAGE Meropenem for Injection is a penem antibacterial indicated for the treatment of: Complicated skin and skin structure infections (adult patients and pediatric patients 3 months of age and older only).
(1.1 ) Complicated intra-abdominal infections (adult and pediatric patients).
( 1.2 ) Bacterial meningitis (pediatric patients 3 months of age and older only).
( 1.3 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of Meropenem for Injection and other antibacterial drugs, Meropenem for Injection should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
1.1 Complicated Skin and Skin Structure Infections (Adult Patients and Pediatric Patients 3 Months of Age and Older Only) Meropenem for Injection is indicated for the treatment of complicated skin and skin structure infections (cSSSI) due to Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae , viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species .
1.2 Complicated Intra-abdominal Infections (Adult and Pediatric Patients) Meropenem for Injection is indicated for the treatment of complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli , Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B.
thetaiotaomicron , and Peptostreptococcus species.
1.3 Bacterial Meningitis (Pediatric Patients 3 Months of Age and Older Only) Meropenem for Injection is indicated for the treatment of bacterial meningitis caused by Haemophilus influenzae, Neisseria meningitidis and penicillin-susceptible isolates of Streptococcus pneumoniae .
Meropenem for Injection has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis.
1.4 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of Meropenem for Injection and other antibacterial drugs, Meropenem for Injection should only be used 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.
(1.1 ) Complicated intra-abdominal infections (adult and pediatric patients).
( 1.2 ) Bacterial meningitis (pediatric patients 3 months of age and older only).
( 1.3 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of Meropenem for Injection and other antibacterial drugs, Meropenem for Injection should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
1.1 Complicated Skin and Skin Structure Infections (Adult Patients and Pediatric Patients 3 Months of Age and Older Only) Meropenem for Injection is indicated for the treatment of complicated skin and skin structure infections (cSSSI) due to Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae , viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species .
1.2 Complicated Intra-abdominal Infections (Adult and Pediatric Patients) Meropenem for Injection is indicated for the treatment of complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli , Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B.
thetaiotaomicron , and Peptostreptococcus species.
1.3 Bacterial Meningitis (Pediatric Patients 3 Months of Age and Older Only) Meropenem for Injection is indicated for the treatment of bacterial meningitis caused by Haemophilus influenzae, Neisseria meningitidis and penicillin-susceptible isolates of Streptococcus pneumoniae .
Meropenem for Injection has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis.
1.4 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of Meropenem for Injection and other antibacterial drugs, Meropenem for Injection should only be used 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 are discussed in greater detail in other sections of labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.2) ] Rhabdomyolysis [see Warnings and Precautions (5.3) ] Seizure Potential [see Warnings and Precautions (5.4) ] Risk of Breakthrough Seizures Due to Drug Interaction with Valproic Acid [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) ] Overgrowth of Nonsusceptible Organisms [see Warnings and Precautions (5.8) ] Thrombocytopenia [see Warnings and Precautions (5.9) ] Potential for Neuromotor Impairment [see Warnings and Precautions (5.10) ] Most common adverse reactions (2% or less) are: headache, nausea, constipation, diarrhea, anemia, vomiting, and rash.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eugia US LLC at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Adverse Reactions from Clinical Trials Because clinical trials are conducted under widely varying conditions, adverse reactions 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.
Adult Patients: During clinical investigations, 2,904 immunocompetent adult patients were treated for non-CNS infections with Meropenem for Injection (500 mg or 1 gram every 8 hours).
Deaths in 5 patients were assessed as possibly related to meropenem; 36 (1.2%) patients had meropenem discontinued because of adverse events.
Many patients in these trials were severely ill and had multiple background diseases, physiological impairments and were receiving multiple other drug therapies.
In the seriously ill patient population, it was not possible to determine the relationship between observed adverse events and therapy with Meropenem for Injection.
The following adverse reaction frequencies were derived from the clinical trials in the 2,904 patients treated with Meropenem for Injection.
Local Adverse Reactions Local adverse events that were reported with Meropenem for Injection were as follows: Inflammation at the injection site 2.4% Injection site reaction 0.9% Phlebitis/thrombophlebitis 0.8% Pain at the injection site 0.4% Edema at the injection site 0.2% Systemic Adverse Reactions Systemic adverse events that were reported with Meropenem for Injection occurring in greater than 1.0% of the patients were diarrhea (4.8%), nausea/vomiting (3.6%), headache (2.3%), rash (1.9%), sepsis (1.6%), constipation (1.4%), apnea (1.3%), shock (1.2%), and pruritus (1.2%).
Additional systemic adverse events that were reported with Meropenem for Injection and occurring in less than or equal to 1.0% but greater than 0.1% of the patients are listed below within each body system in order of decreasing frequency: Bleeding events were seen as follows: gastrointestinal hemorrhage (0.5%), melena (0.3%), epistaxis (0.2%), hemoperitoneum (0.2%).
Body as a Whole: pain, abdominal pain, chest pain, fever, back pain, abdominal enlargement, chills, pelvic pain Cardiovascular: heart failure, heart arrest, tachycardia, hypertension, myocardial infarction, pulmonary embolus, bradycardia, hypotension, syncope Digestive System: oral moniliasis, anorexia, cholestatic jaundice/jaundice, flatulence, ileus, hepatic failure, dyspepsia, intestinal obstruction Hemic/Lymphatic: anemia, hypochromic anemia, hypervolemia Metabolic/Nutritional: peripheral edema, hypoxia Nervous System: insomnia, agitation, delirium, confusion, dizziness, seizure, nervousness, paresthesia, hallucinations, somnolence, anxiety, depression, asthenia [see Warnings and Precautions (5.4) and (5.10) ] Respiratory: respiratory disorder, dyspnea, pleural effusion, asthma, cough increased, lung edema Skin and Appendages: urticaria, sweating, skin ulcer Urogenital System: dysuria, kidney failure, vaginal moniliasis, urinary incontinence Adverse Laboratory Changes Adverse laboratory changes that were reported and occurring in greater than 0.2% of the patients were as follows: Hepatic: increased alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, lactate dehydrogenase (LDH), and bilirubin Hematologic: increased platelets, increased eosinophils, decreased platelets, decreased hemoglobin, decreased hematocrit, decreased white blood cell (WBC), shortened prothrombin time and shortened partial thromboplastin time, leukocytosis, hypokalemia Renal: increased creatinine and increased blood urea nitrogen (BUN) Urinalysis: presence of red blood cells Complicated Skin and Skin Structure Infections In a study of complicated skin and skin structure infections, the adverse reactions were similar to those listed above.
The most common adverse events occurring in greater than 5% of the patients were: headache (7.8%), nausea (7.8%), constipation (7.0%), diarrhea (7.0%), anemia (5.5%), and pain (5.1%).
Adverse events with an incidence of greater than 1%, and not listed above, include: pharyngitis, accidental injury, gastrointestinal disorder, hypoglycemia, peripheral vascular disorder, and pneumonia.
Patients with Renal Impairment: For patients with varying degrees of renal impairment, the incidence of heart failure, kidney failure, seizure and shock reported with Meropenem for Injection, increased in patients with moderately severe renal impairment (creatinine clearance 10 to 26 mL/min) [see Dosage and Administration (2.2) , Warnings and Precautions (5.10) , Use in Specific Populations (8.5) and (8.6) and Clinical Pharmacology (12.3) ] .
Pediatric Patients: Systemic and Local Adverse Reactions Pediatric Patients with Serious Bacterial Infections (excluding Bacterial Meningitis): Meropenem for Injection was studied in 515 pediatric patients (3 months to less than 13 years of age) with serious bacterial infections (excluding meningitis, see next section) at dosages of 10 mg/kg to 20 mg/kg every 8 hours.
The types of systemic and local adverse events seen in these patients are similar to the adults, with the most common adverse events reported as possibly, probably, or definitely related to Meropenem for Injection and their rates of occurrence as follows: Diarrhea 3.5% Rash 1.6% Nausea and Vomiting 0.8% Pediatric Patients with Bacterial Meningitis : Meropenem for Injection was studied in 321 pediatric patients (3 months to less than 17 years of age) with meningitis at a dosage of 40 mg/kg every 8 hours.
The types of systemic and local adverse events seen in these patients are similar to the adults, with the most common adverse reactions reported as possibly, probably, or definitely related to Meropenem for Injection and their rates of occurrence as follows: Diarrhea 4.7% Rash (mostly diaper area moniliasis) 3.1% Oral Moniliasis 1.9% Glossitis 1.0% In the meningitis studies, the rates of seizure activity during therapy were comparable between patients with no CNS abnormalities who received meropenem and those who received comparator agents (either cefotaxime or ceftriaxone).
In the Meropenem for Injection treated group, 12/15 patients with seizures had late onset seizures (defined as occurring on day 3 or later) versus 7/20 in the comparator arm.
The meropenem group had a statistically higher number of patients with transient elevation of liver enzymes.
Pediatric Patients (Neonates and Infants less than 3 months of Age): Meropenem for Injection was studied in 200 neonates and infants less than 3 months of age.
The study was open-label, uncontrolled, 98% of the infants received concomitant medications, and the majority of adverse events were reported in neonates less than 32 weeks gestational age and critically ill at baseline, making it difficult to assess the relationship of the adverse events to Meropenem for Injection.
The adverse reactions seen in these patients that were reported and their rates of occurrence are as follows: Convulsion 5.0% Hyperbilirubinemia (conjugated) 4.5% Vomiting 2.5% Adverse Laboratory Changes in Pediatric Patients: Laboratory changes seen in the pediatric studies, including the meningitis studies, were similar to those reported in the adult studies.
6.2 Post marketing Experience The following adverse reactions have been identified during post-approval use of meropenem, including Meropenem for Injection.
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.
Worldwide post-marketing adverse reactions not otherwise listed in the Adverse Reactions from Clinical Trials section of this prescribing information and reported as possibly, probably, or definitely drug related are listed within each body system in order of decreasing severity.
Blood and Lymphatic System Disorders : agranulocytosis, neutropenia, and leukopenia; a positive direct or indirect Coombs test, and hemolytic anemia.
Immune System Disorders : angioedema.
Skin and Subcutaneous Disorders : Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme and acute generalized exanthematous pustulosis.
Musculoskeletal Disorders: rhabdomyolysis.
Hepatic Disorders : drug-induced liver injury.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eugia US LLC at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Adverse Reactions from Clinical Trials Because clinical trials are conducted under widely varying conditions, adverse reactions 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.
Adult Patients: During clinical investigations, 2,904 immunocompetent adult patients were treated for non-CNS infections with Meropenem for Injection (500 mg or 1 gram every 8 hours).
Deaths in 5 patients were assessed as possibly related to meropenem; 36 (1.2%) patients had meropenem discontinued because of adverse events.
Many patients in these trials were severely ill and had multiple background diseases, physiological impairments and were receiving multiple other drug therapies.
In the seriously ill patient population, it was not possible to determine the relationship between observed adverse events and therapy with Meropenem for Injection.
The following adverse reaction frequencies were derived from the clinical trials in the 2,904 patients treated with Meropenem for Injection.
Local Adverse Reactions Local adverse events that were reported with Meropenem for Injection were as follows: Inflammation at the injection site 2.4% Injection site reaction 0.9% Phlebitis/thrombophlebitis 0.8% Pain at the injection site 0.4% Edema at the injection site 0.2% Systemic Adverse Reactions Systemic adverse events that were reported with Meropenem for Injection occurring in greater than 1.0% of the patients were diarrhea (4.8%), nausea/vomiting (3.6%), headache (2.3%), rash (1.9%), sepsis (1.6%), constipation (1.4%), apnea (1.3%), shock (1.2%), and pruritus (1.2%).
Additional systemic adverse events that were reported with Meropenem for Injection and occurring in less than or equal to 1.0% but greater than 0.1% of the patients are listed below within each body system in order of decreasing frequency: Bleeding events were seen as follows: gastrointestinal hemorrhage (0.5%), melena (0.3%), epistaxis (0.2%), hemoperitoneum (0.2%).
Body as a Whole: pain, abdominal pain, chest pain, fever, back pain, abdominal enlargement, chills, pelvic pain Cardiovascular: heart failure, heart arrest, tachycardia, hypertension, myocardial infarction, pulmonary embolus, bradycardia, hypotension, syncope Digestive System: oral moniliasis, anorexia, cholestatic jaundice/jaundice, flatulence, ileus, hepatic failure, dyspepsia, intestinal obstruction Hemic/Lymphatic: anemia, hypochromic anemia, hypervolemia Metabolic/Nutritional: peripheral edema, hypoxia Nervous System: insomnia, agitation, delirium, confusion, dizziness, seizure, nervousness, paresthesia, hallucinations, somnolence, anxiety, depression, asthenia [see Warnings and Precautions (5.4) and (5.10) ] Respiratory: respiratory disorder, dyspnea, pleural effusion, asthma, cough increased, lung edema Skin and Appendages: urticaria, sweating, skin ulcer Urogenital System: dysuria, kidney failure, vaginal moniliasis, urinary incontinence Adverse Laboratory Changes Adverse laboratory changes that were reported and occurring in greater than 0.2% of the patients were as follows: Hepatic: increased alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, lactate dehydrogenase (LDH), and bilirubin Hematologic: increased platelets, increased eosinophils, decreased platelets, decreased hemoglobin, decreased hematocrit, decreased white blood cell (WBC), shortened prothrombin time and shortened partial thromboplastin time, leukocytosis, hypokalemia Renal: increased creatinine and increased blood urea nitrogen (BUN) Urinalysis: presence of red blood cells Complicated Skin and Skin Structure Infections In a study of complicated skin and skin structure infections, the adverse reactions were similar to those listed above.
The most common adverse events occurring in greater than 5% of the patients were: headache (7.8%), nausea (7.8%), constipation (7.0%), diarrhea (7.0%), anemia (5.5%), and pain (5.1%).
Adverse events with an incidence of greater than 1%, and not listed above, include: pharyngitis, accidental injury, gastrointestinal disorder, hypoglycemia, peripheral vascular disorder, and pneumonia.
Patients with Renal Impairment: For patients with varying degrees of renal impairment, the incidence of heart failure, kidney failure, seizure and shock reported with Meropenem for Injection, increased in patients with moderately severe renal impairment (creatinine clearance 10 to 26 mL/min) [see Dosage and Administration (2.2) , Warnings and Precautions (5.10) , Use in Specific Populations (8.5) and (8.6) and Clinical Pharmacology (12.3) ] .
Pediatric Patients: Systemic and Local Adverse Reactions Pediatric Patients with Serious Bacterial Infections (excluding Bacterial Meningitis): Meropenem for Injection was studied in 515 pediatric patients (3 months to less than 13 years of age) with serious bacterial infections (excluding meningitis, see next section) at dosages of 10 mg/kg to 20 mg/kg every 8 hours.
The types of systemic and local adverse events seen in these patients are similar to the adults, with the most common adverse events reported as possibly, probably, or definitely related to Meropenem for Injection and their rates of occurrence as follows: Diarrhea 3.5% Rash 1.6% Nausea and Vomiting 0.8% Pediatric Patients with Bacterial Meningitis : Meropenem for Injection was studied in 321 pediatric patients (3 months to less than 17 years of age) with meningitis at a dosage of 40 mg/kg every 8 hours.
The types of systemic and local adverse events seen in these patients are similar to the adults, with the most common adverse reactions reported as possibly, probably, or definitely related to Meropenem for Injection and their rates of occurrence as follows: Diarrhea 4.7% Rash (mostly diaper area moniliasis) 3.1% Oral Moniliasis 1.9% Glossitis 1.0% In the meningitis studies, the rates of seizure activity during therapy were comparable between patients with no CNS abnormalities who received meropenem and those who received comparator agents (either cefotaxime or ceftriaxone).
In the Meropenem for Injection treated group, 12/15 patients with seizures had late onset seizures (defined as occurring on day 3 or later) versus 7/20 in the comparator arm.
The meropenem group had a statistically higher number of patients with transient elevation of liver enzymes.
Pediatric Patients (Neonates and Infants less than 3 months of Age): Meropenem for Injection was studied in 200 neonates and infants less than 3 months of age.
The study was open-label, uncontrolled, 98% of the infants received concomitant medications, and the majority of adverse events were reported in neonates less than 32 weeks gestational age and critically ill at baseline, making it difficult to assess the relationship of the adverse events to Meropenem for Injection.
The adverse reactions seen in these patients that were reported and their rates of occurrence are as follows: Convulsion 5.0% Hyperbilirubinemia (conjugated) 4.5% Vomiting 2.5% Adverse Laboratory Changes in Pediatric Patients: Laboratory changes seen in the pediatric studies, including the meningitis studies, were similar to those reported in the adult studies.
6.2 Post marketing Experience The following adverse reactions have been identified during post-approval use of meropenem, including Meropenem for Injection.
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.
Worldwide post-marketing adverse reactions not otherwise listed in the Adverse Reactions from Clinical Trials section of this prescribing information and reported as possibly, probably, or definitely drug related are listed within each body system in order of decreasing severity.
Blood and Lymphatic System Disorders : agranulocytosis, neutropenia, and leukopenia; a positive direct or indirect Coombs test, and hemolytic anemia.
Immune System Disorders : angioedema.
Skin and Subcutaneous Disorders : Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme and acute generalized exanthematous pustulosis.
Musculoskeletal Disorders: rhabdomyolysis.
Hepatic Disorders : drug-induced liver injury.