Ertapenem

Prevention

Ertapenem for injection is indicated in adults for:

For Intravenous or Intramuscular Use

DO NOT MIX OR CO-INFUSE ERTAPENEM FOR INJECTION WITH OTHER MEDICATIONS. DO NOT USE DILUENTS CONTAINING DEXTROSE (α -D-GLUCOSE).

Ertapenem for injection may be administered by intravenous infusion for up to 14 days or intramuscular injection for up to 7 days. When administered intravenously, Ertapenem for injection should be infused over a period of 30 minutes. Intramuscular administration of Ertapenem for injection may be used as an alternative to intravenous administration in the treatment of those infections for which intramuscular therapy is appropriate.

13 years of age and older

The dose of Ertapenem for injection in patients 13 years of age and older is 1 gram (g) given once a day [see Clinical Pharmacology (12.3)].

3 months to 12 years of age

The dose of Ertapenem for injection in patients 3 months to 12 years of age is 15 mg/kg twice daily (not to exceed 1 g/day).

Table 1 presents treatment guidelines for Ertapenem for injection.

Vials

Adults Receiving Ertapenem for injection as a Treatment Regimen

Clinical trials enrolled 1954 patients treated with Ertapenem for injection; in some of the clinical trials, parenteral therapy was followed by a switch to an appropriate oral antimicrobial [see Clinical Studies (14)]. Most adverse experiences reported in these clinical trials were described as mild to moderate in severity. Ertapenem for injection was discontinued due to adverse experiences in 4.7% of patients. Table 3 shows the incidence of adverse experiences reported in ≥2.0% of patients in these trials. The most common drug-related adverse experiences in patients treated with Ertapenem for injection, including those who were switched to therapy with an oral antimicrobial, were diarrhea (5.5%), infused vein complication (3.7%), nausea (3.1%), headache (2.2%), and vaginitis in females (2.1%).

In patients treated for complicated intra-abdominal infections, death occurred in 4.7% (15/316) of patients receiving Ertapenem for injection and 2.6% (8/307) of patients receiving comparator drug. These deaths occurred in patients with significant co-morbidity and/or severe baseline infections. Deaths were considered unrelated to study drugs by investigators.

In clinical trials, seizure was reported during study therapy plus 14-day follow-up period in 0.5% of patients treated with Ertapenem for injection, 0.3% of patients treated with piperacillin/tazobactam and 0% of patients treated with ceftriaxone [see Warnings and Precautions (5.2)].

Additional adverse experiences that were reported with Ertapenem for injection with an incidence >0.1% within each body system are listed below

Body as a Whole: abdominal distention, pain, chills, septicemia, septic shock, dehydration, gout, malaise, asthenia/fatigue, necrosis, candidiasis, weight loss, facial edema, injection site induration, injection site pain, extravasation, phlebitis/thrombophlebitis, flank pain, syncope

Cardiovascular System: heart failure, hematoma, chest pain, hypertension, tachycardia, cardiac arrest, bradycardia, arrhythmia, atrial fibrillation, heart murmur, ventricular tachycardia, asystole, subdural hemorrhage

Digestive System: acid regurgitation, oral candidiasis, dyspepsia, gastrointestinal hemorrhage, anorexia, flatulence, C. difficile-associated diarrhea, stomatitis, dysphagia, hemorrhoids, ileus, cholelithiasis, duodenitis, esophagitis, gastritis, jaundice, mouth ulcer, pancreatitis, pyloric stenosis

Musculoskeletal System: leg pain

Nervous System & Psychiatric: anxiety, nervousness, seizure [see Warnings and Precautions (5.2)] , tremor, depression, hypesthesia, spasm, paresthesia, aggressive behavior, vertigo

Respiratory System: cough, pharyngitis, rales/rhonchi, respiratory distress, pleural effusion, hypoxemia, bronchoconstriction, pharyngeal discomfort, epistaxis, pleuritic pain, asthma, hemoptysis, hiccups, voice disturbance

Skin & Skin Appendage: erythema, sweating, dermatitis, desquamation, flushing, urticaria

Special Senses: taste perversion

Urogenital System: renal impairment, oliguria/anuria, vaginal pruritus, hematuria, urinary retention, bladder dysfunction, vaginal candidiasis, vulvovaginitis.

In a clinical trial for the treatment of diabetic foot infections in which 289 adult diabetic patients were treated with Ertapenem for injection, the adverse experience profile was generally similar to that seen in previous clinical trials.

Prophylaxis of Surgical Site Infection following Elective Colorectal Surgery

In a clinical trial in adults for the prophylaxis of surgical site infection following elective colorectal surgery in which 476 patients received a 1 g dose of Ertapenem for injection 1 hour prior to surgery and were then followed for safety 14 days post-surgery, the overall adverse experience profile was generally comparable to that observed for Ertapenem for injection in previous clinical trials. Table 4 shows the incidence of adverse experiences other than those previously described above for Ertapenem for injection that were reported regardless of causality in ≥2.0% of patients in this trial.

Additional adverse experiences that were reported in this prophylaxis trial with Ertapenem for injection, regardless of causality, with an incidence >0.5% within each body system are listed below:

Gastrointestinal Disorders: C. difficile infection or colitis, dry mouth, hematochezia

General Disorders and Administration Site Condition: crepitations

Infections and Infestations: cellulitis, abdominal abscess, fungal rash, pelvic abscess

Injury, Poisoning and Procedural Complications: incision site complication, incision site hemorrhage, intestinal stoma complication, anastomotic leak, seroma, wound dehiscence, wound secretion

Musculoskeletal and Connective Tissue Disorders: muscle spasms

Nervous System Disorders: cerebrovascular accident

Renal and Urinary Disorders: dysuria, pollakiuria

Respiratory, Thoracic and Mediastinal Disorders: crackles lung, lung infiltration, pulmonary congestion, pulmonary embolism, wheezing.

Pediatric Patients Receiving Ertapenem for injection as a Treatment Regimen

Clinical trials enrolled 384 patients treated with Ertapenem for injection; in some of the clinical trials, parenteral therapy was followed by a switch to an appropriate oral antimicrobial [see Clinical Studies (14)]. The overall adverse experience profile in pediatric patients is comparable to that in adult patients. Table 5 shows the incidence of adverse experiences reported in ≥2.0% of pediatric patients in clinical trials. The most common drug-related adverse experiences in pediatric patients treated with Ertapenem for injection, including those who were switched to therapy with an oral antimicrobial, were diarrhea (6.5%), infusion site pain (5.5%), infusion site erythema (2.6%), vomiting (2.1%).

Additional adverse experiences that were reported with Ertapenem for injection with an incidence >0.5% within each body system are listed below:

Gastrointestinal Disorders: nausea

General Disorders and Administration Site Condition: hypothermia, chest pain, upper abdominal pain; infusion site pruritus, induration, phlebitis, swelling, and warmth

Infections and Infestations: candidiasis, oral candidiasis, viral pharyngitis, herpes simplex, ear infection, abdominal abscess

Metabolism and Nutrition Disorders: decreased appetite Musculoskeletal and Connective Tissue Disorders: arthralgia Nervous System Disorders: dizziness, somnolence

Psychiatric Disorders: insomnia

Reproductive System and Breast Disorders: genital rash

Respiratory, Thoracic and Mediastinal Disorders: wheezing, nasopharyngitis, pleural effusion, rhinitis, rhinorrhea

Skin and Subcutaneous Tissue Disorders: dermatitis, pruritus, rash erythematous, skin lesion

Vascular Disorders: phlebitis.

Adults Receiving Ertapenem for injection as Treatment Regimen

Laboratory adverse experiences that were reported during therapy in ≥2.0% of adult patients treated with Ertapenem for injection in clinical trials are presented in Table 6. Drug-related laboratory adverse experiences that were reported during therapy in ≥2.0% of adult patients treated with Ertapenem for injection, including those who were switched to therapy with an oral antimicrobial, in clinical trials were ALT increased (6.0%), AST increased (5.2%), serum alkaline phosphatase increased (3.4%), and platelet count increased (2.8%). Ertapenem for injection was discontinued due to laboratory adverse experiences in 0.3% of patients.

Additional laboratory adverse experiences that were reported during therapy in >0.1% of patients treated with Ertapenem for injection in clinical trials include: increases in serum creatinine, serum glucose, BUN, total, direct and indirect serum bilirubin, serum sodium and potassium, PT and PTT; decreases in serum potassium, serum albumin, WBC, platelet count, and segmented neutrophils.

In a clinical trial for the treatment of diabetic foot infections in which 289 adult diabetic patients were treated with Ertapenem for injection, the laboratory adverse experience profile was generally similar to that seen in previous clinical trials.

Prophylaxis of Surgical Site Infection following Elective Colorectal Surgery

In a clinical trial in adults for the prophylaxis of surgical site infection following elective colorectal surgery in which 476 patients received a 1 g dose of Ertapenem for injection 1 hour prior to surgery and were then followed for safety 14 days post-surgery, the overall laboratory adverse experience profile was generally comparable to that observed for Ertapenem for injection in previous clinical trials.

Pediatric Patients Receiving Ertapenem for injection as a Treatment Regimen

Laboratory adverse experiences that were reported during therapy in ≥2.0% of pediatric patients treated with Ertapenem for injection in clinical trials are presented in Table 7. Drug-related laboratory adverse experiences that were reported during therapy in ≥2.0% of pediatric patients treated with Ertapenem for injection, including those who were switched to therapy with an oral antimicrobial, in clinical trials were neutrophil count decreased (3.0%), ALT increased (2.2%), and AST increased (2.1%).

Additional laboratory adverse experiences that were reported during therapy in >0.5% of patients treated with Ertapenem for injection in clinical trials include: alkaline phosphatase increased, eosinophil count increased, platelet count increased, white blood cell count decreased and urine protein present.

Risk Summary

Available data from a small number of post-marketing cases with Ertapenem for injection use in pregnancy are insufficient to inform any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies after intravenous administration of ertapenem during the period of organogenesis, there was no evidence of developmental malformations in rats at systemic exposures (AUC) up to approximately 1.2 times the human exposure at the maximum recommended human dose (MRHD) and in mice at doses up to approximately 3 times the MRHD based on body surface area comparison. In pregnant rats administered ertapenem during organogenesis through lactation, fetal toxicity, developmental delays, and impaired reproduction did not occur in first generation offspring at systemic exposures (AUC) approximately 1.2 times the human exposure at the MRHD (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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.

Data
Animal Data

In pregnant rats, intravenous administration of ertapenem dosages of up to 700 mg/kg/day (approximately 1.2 times the MRHD based on AUC) during the period of organogenesis (gestation days [GD] 6-20) revealed no maternal or embryofetal effects.

Pregnant mice intravenously administered ertapenem dosages of up to 700 mg/kg/day (approximately 3 times the MRHD based on body surface area comparison) during the period of organogenesis (GD 6-15) showed slight decreases in average fetal weight and an associated decrease in the average number of ossified sacrocaudal vertebrae. There were no maternal effects at any dosage.

In a pre-postnatal study in rats, ertapenem administered to pregnant rats at dosages up to 700 mg/kg/day (approximately 1.2 times the MRHD based on AUC) during organogenesis through lactation, (GD 6 until Lactation Day (LD) 20) did not result in fetal toxicity, developmental delays, or impaired reproduction in first generation offspring, and fetal deaths and malformations were not increased in second generation offspring.

Absorption

Ertapenem, reconstituted with 1% lidocaine HCl injection, USP (in saline without epinephrine), is almost completely absorbed following intramuscular (IM) administration at the recommended dose of 1 g. The mean bioavailability is approximately 90%. Following 1 g daily IM administration, mean peak plasma concentrations (C _max) are achieved in approximately 2.3 hours (T _max).

Distribution

Ertapenem is highly bound to human plasma proteins, primarily albumin. In healthy young adults, the protein binding of ertapenem decreases as plasma concentrations increase, from approximately 95% bound at an approximate plasma concentration of <100 micrograms (mcg)/mL to approximately 85% bound at an approximate plasma concentration of 300 mcg/mL.

The apparent volume of distribution at steady state (V _ss) of ertapenem in adults is approximately 0.12 liter/kg, approximately 0.2 liter/kg in pediatric patients 3 months to 12 years of age and approximately 0.16 liter/kg in pediatric patients 13 to 17 years of age.

The concentrations of ertapenem achieved in suction-induced skin blister fluid at each sampling point on the third day of 1 g once daily IV doses are presented in Table 10. The ratio of AUC _0-24 in skin blister fluid/AUC _0-24 in plasma is 0.61.

Metabolism

In healthy young adults, after infusion of 1 g IV radiolabeled ertapenem, the plasma radioactivity consists predominantly (94%) of ertapenem. The major metabolite of ertapenem is the inactive ring- opened derivative formed by hydrolysis of the beta-lactam ring.

Elimination

Ertapenem is eliminated primarily by the kidneys. The mean plasma half-life in healthy young adults is approximately 4 hours and the plasma clearance is approximately 1.8 L/hour. The mean plasma half-life in pediatric patients 13 to 17 years of age is approximately 4 hours and approximately 2.5 hours in pediatric patients 3 months to 12 years of age.

Following the administration of 1 g IV radiolabeled ertapenem to healthy young adults, approximately 80% is recovered in urine and 10% in feces. Of the 80% recovered in urine, approximately 38% is excreted as unchanged drug and approximately 37% as the ring-opened metabolite.

In healthy young adults given a 1 g IV dose, the mean percentage of the administered dose excreted in urine was 17.4% during 0-2 hours postdose, 5.4% during 4-6 hours postdose, and 2.4% during 12-24 hours postdose.

Special Populations

Drug Interactions

When ertapenem is co-administered with probenecid (500 mg p.o. every 6 hours), probenecid competes for active tubular secretion and reduces the renal clearance of ertapenem. Based on total ertapenem concentrations, probenecid increased the AUC of ertapenem by 25%, and reduced the plasma and renal clearance of ertapenem by 20% and 35%, respectively. The half-life of ertapenem was increased from 4.0 to 4.8 hours.

In vitro studies in human liver microsomes indicate that ertapenem does not inhibit metabolism mediated by any of the following cytochrome p450 (CYP) isoforms: 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4.

In vitro studies indicate that ertapenem does not inhibit P-glycoprotein-mediated transport of digoxin or vinblastine and that ertapenem is not a substrate for P-glycoprotein-mediated transport.

Mechanism of Action

Ertapenem has in vitro activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria. The bactericidal activity of ertapenem results from the inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin binding proteins (PBPs). In Escherichia coli, it has strong affinity toward PBPs 1a, 1b, 2, 3, 4 and 5 with preference for PBPs 2 and 3.

Resistance

Ertapenem is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. Ertapenem is hydrolyzed by metallo-beta-lactamases.

Antimicrobial Activity

Ertapenem has been shown to be active against most isolates of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section :

Gram-positive bacteria:

Staphylococcus aureus (methicillin susceptible isolates only)

Streptococcus agalactiae

Streptococcus pneumoniae (penicillin susceptible isolates only)

Streptococcus pyogenes

Gram-negative bacteria:

Escherichia coli

Haemophilus influenzae (beta-lactamase negative isolates only)

Klebsiella pneumoniae

Moraxella catarrhalis

Proteus mirabilis

Anaerobic bacteria:

Bacteroides fragilis

Bacteroides distasonis

Bacteroides ovatus

Bacteroides thetaiotaomicron

Bacteroides uniformis

Clostridium clostridioforme

Eubacterium lentum

Peptostreptococcus species

Porphyromonas asaccharolytica

Prevotella bivia

The following in vitro data are available, but their clinical significance is unknown. At least 90% of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ertapenem. However, the efficacy of ertapenem in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials:

Gram-positive bacteria:

Staphylococcus epidermidis (methicillin susceptible isolates only)

Streptococcus pneumoniae (penicillin-intermediate isolates)

Gram-negative bacteria:

Citrobacter freundii

Citrobacter koseri

Enterobacter aerogenes

Enterobacter cloacae

Haemophilus influenzae (beta-lactamase positive isolates only)

Haemophilus parainfluenzae

Klebsiella oxytoca (excluding ESBL producing isolates)

Morganella morganii

Proteus vulgaris

Providencia rettgeri

Providencia stuartii

Serratia marcescens

Anaerobic bacteria:

Bacteroides vulgatus

Clostridium perfringens

Fusobacterium spp.

Susceptibility Testing

For specific information regarding susceptibility testing methods, interpretive criteria, and associated test methods and quality control standards recognized by FDA for ertapenem, please see  www.fda.gov/STIC.

Complicated Intra-Abdominal Infections

Ertapenem was evaluated in adults for the treatment of complicated intra-abdominal infections in a randomized, double-blind, non-inferiority clinical trial. This trial compared ertapenem (1 g intravenously once a day) with piperacillin/tazobactam (3.375 g intravenously every 6 hours) for 5 to 14 days and enrolled 665 patients with localized complicated appendicitis, and any other complicated intra-abdominal infection including colonic, small intestinal, and biliary infections and generalized peritonitis. The combined clinical and microbiologic success rates in the microbiologically evaluable population at 4 to 6 weeks posttherapy (test-of-cure) were 83.6% (163/195) for ertapenem and 80.4% (152/189) for piperacillin/tazobactam.

Complicated Skin and Skin Structure Infections

Ertapenem was evaluated in adults for the treatment of complicated skin and skin structure infections in a randomized, double-blind, non-inferiority clinical trial. This trial compared ertapenem (1 g intravenously once a day) with piperacillin/tazobactam (3.375 g intravenously every 6 hours) for 7 to 14 days and enrolled 540 patients including patients with deep soft tissue abscess, posttraumatic wound infection and cellulitis with purulent drainage. The clinical success rates at 10 to 21 days posttherapy (test-of-cure) were 83.9% (141/168) for ertapenem and 85.3% (145/170) for piperacillin/tazobactam.

Diabetic Foot Infections

Ertapenem was evaluated in adults for the treatment of diabetic foot infections without concomitant osteomyelitis in a multicenter, randomized, double-blind, non-inferiority clinical trial. This trial compared ertapenem (1 g intravenously once a day) with piperacillin/tazobactam (3.375 g intravenously every 6 hours). Test-of-cure was defined as clinical response between treatment groups in the clinically evaluable population at the 10-day posttherapy follow-up visit. The trial included 295 patients randomized to ertapenem and 291 patients to piperacillin/tazobactam. Both regimens allowed the option to switch to oral amoxicillin/clavulanate for a total of 5 to 28 days of treatment (parenteral and oral). All patients were eligible to receive appropriate adjunctive treatment methods, such as debridement, as is typically required in the treatment of diabetic foot infections, and most patients received these treatments. Patients with suspected osteomyelitis could be enrolled if all the infected bone was removed within 2 days of initiation of study therapy, and preferably within the prestudy period. Investigators had the option to add open-label vancomycin if enterococci or methicillin-resistant Staphylococcus aureus (MRSA) were among the pathogens isolated or if patients had a history of MRSA infection and additional therapy was indicated in the opinion of the investigator. Two hundred and four (204) patients randomized to ertapenem and 202 patients randomized to piperacillin/tazobactam were clinically evaluable. The clinical success rates at 10 days posttherapy were 75.0% (153/204) for ertapenem and 70.8% (143/202) for piperacillin/tazobactam.

Community Acquired Pneumonia

Ertapenem was evaluated in adults for the treatment of community acquired pneumonia in two randomized, double-blind, non-inferiority clinical trials. Both trials compared ertapenem (1 g parenterally once a day) with ceftriaxone (1 g parenterally once a day) and enrolled a total of 866 patients. Both regimens allowed the option to switch to oral amoxicillin/clavulanate for a total of 10 to 14 days of treatment (parenteral and oral). In the first trial the primary efficacy parameter was the clinical success rate in the clinically evaluable population and success rates were 92.3% (168/182) for ertapenem and 91.0% (183/201) for ceftriaxone at 7 to 14 days posttherapy (test-of-cure). In the second trial the primary efficacy parameter was the clinical success rate in the microbiologically evaluable population and success rates were 91% (91/100) for ertapenem and 91.8% (45/49) for ceftriaxone at 7 to 14 days posttherapy (test-of-cure).

Complicated Urinary Tract Infections Including Pyelonephritis

Ertapenem was evaluated in adults for the treatment of complicated urinary tract infections including pyelonephritis in two randomized, double-blind, non-inferiority clinical trials. Both trials compared ertapenem (1 g parenterally once a day) with ceftriaxone (1 g parenterally once a day) and enrolled a total of 850 patients. Both regimens allowed the option to switch to oral ciprofloxacin (500 mg twice daily) for a total of 10 to 14 days of treatment (parenteral and oral). The microbiological success rates (combined trials) at 5 to 9 days posttherapy (test-of-cure) were 89.5% (229/256) for ertapenem and 91.1% (204/224) for ceftriaxone.

Acute Pelvic Infections Including Endomyometritis, Septic Abortion and Post-Surgical Gynecological Infections

Ertapenem was evaluated in adults for the treatment of acute pelvic infections in a randomized, double-blind, non-inferiority clinical trial. This trial compared ertapenem (1 g intravenously once a day) with piperacillin/tazobactam (3.375 g intravenously every 6 hours) for 3 to 10 days and enrolled 412 patients including 350 patients with obstetric/postpartum infections and 45 patients with septic abortion. The clinical success rates in the clinically evaluable population at 2 to 4 weeks posttherapy (test-of-cure) were 93.9% (153/163) for ertapenem and 91.5% (140/153) for piperacillin/tazobactam.

Prophylaxis of Surgical Site Infections Following Elective Colorectal Surgery

Ertapenem was evaluated in adults for prophylaxis of surgical site infection following elective colorectal surgery in a multicenter, randomized, double-blind, non-inferiority clinical trial. This trial compared a single intravenous dose of ertapenem (1 g) versus cefotetan (2 g) administered over 30 minutes, 1 hour before elective colorectal surgery. Test-of-prophylaxis was defined as no evidence of surgical site infection, post-operative anastomotic leak, or unexplained antibiotic use in the clinically evaluable population up to and including at the 4-week posttreatment follow-up visit. The trial included 500 patients randomized to ertapenem and 502 patients randomized to cefotetan. The modified intent-to-treat (MITT) population consisted of 451 ertapenem patients and 450 cefotetan patients and included all patients who were randomized, treated, and underwent elective colorectal surgery with adequate bowel preparation. The clinically evaluable population was a subset of the MITT population and consisted of patients who received a complete dose of study therapy no more than two hours prior to surgical incision and no more than six hours before surgical closure. Clinically evaluable patients had sufficient information to determine outcome at the 4-week follow-up assessment and had no confounding factors that interfered with the assessment of that outcome. Examples of confounding factors included prior or concomitant antibiotic violations, the need for a second surgical procedure during the study period, and identification of a distant site infection with concomitant antibiotic administration and no evidence of subsequent wound infection. Three-hundred forty-six (346) patients randomized to ertapenem and 339 patients randomized to cefotetan were clinically evaluable. The prophylactic success rates at 4 weeks posttreatment in the clinically evaluable population were 70.5% (244/346) for ertapenem and 57.2% (194/339) for cefotetan (difference 13.3%, [95% C.I.: 6.1, 20.4], p<0.001). Prophylaxis failure due to surgical site infections occurred in 18.2% (63/346) ertapenem patients and 31.0% (105/339) cefotetan patients. Post-operative anastomotic leak occurred in 2.9% (10/346) ertapenem patients and 4.1% (14/339) cefotetan patients. Unexplained antibiotic use occurred in 8.4% (29/346) ertapenem patients and 7.7% (26/339) cefotetan patients. Though patient numbers were small in some subgroups, in general, clinical response rates by age, gender, and race were consistent with the results found in the clinically evaluable population. In the MITT analysis, the prophylactic success rates at 4 weeks posttreatment were 58.3% (263/451) for ertapenem and 48.9% (220/450) for cefotetan (difference 9.4%, [95% C.I.: 2.9, 15.9], p=0.002). A statistically significant difference favoring ertapenem over cefotetan with respect to the primary endpoint has been observed at a significance level of 5% in this trial. A second adequate and well-controlled trial to confirm these findings has not been conducted; therefore, the clinical superiority of ertapenem over cefotetan has not been demonstrated.

Before reconstitution

Do not store lyophilized powder above 25°C (77°F).

Reconstituted and infusion solutions

The reconstituted solution, immediately diluted in 0.9% Sodium Chloride Injection [see Dosage and Administration (2.7)], may be stored at room temperature (25°C) and used within 6 hours or stored for 24 hours under refrigeration (5°C) and used within 4 hours after removal from refrigeration. Solutions of Ertapenem for injection should not be frozen.