Invanz

— THERAPEUTIC CATEGORIES —
  • Bacterial infections
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Invanz Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Ertapenem (as sodium) 1g; pwd for IV infusion after reconstitution and dilution; or for IM inj after reconstitution; sodium content 6mEq/g.

    Pharmacological Class

    Carbapenem.

    How Supplied

    Vials—10

    How Supplied

    Invanz is supplied as a sterile lyophilized powder in single-dose vials containing ertapenem for intravenous infusion or for intramuscular injection as follows: 1 g ertapenem equivalent in trays of 10 vials.

    Storage

    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, 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 Invanz should not be frozen. 

    Manufacturer

    Merck & Co., Inc.

    Generic Availability

    NO

    Mechanism of Action

    Ertapenem has in vitro activity against Gram (+) and Gram (-) 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.

    Invanz Indications

    Indications

    Susceptible moderate to severe infections including complicated intraabdominal, complicated skin and skin structure, community-acquired pneumonia, complicated UTIs, acute pelvic infections. Prevention of surgical site infection following elective colorectal surgery in adults.

    Invanz Dosage and Administration

    Adults and Children

    Do not mix or co-infuse with other meds or diluents containing dextrose. Give by IV infusion over 30 minutes for up to 14 days; or, give by IM inj for up to 7 days (for IM: see note). <3months: not recommended. 3months–12yrs: 15mg/kg twice daily (max 1g/day). ≥13yrs: 1g once daily; renal dysfunction (CrCl ≤30mL/min): 500mg once daily (give supplemental 150mg after session if dosed within 6 hours of hemodialysis). Intraabdominal: treat 5–14 days. Skin and skin structure: treat 7–14 days. Pneumonia, UTIs: treat 10–14 days (may switch to oral antibiotic after 3 days). Pelvic: treat 3–10 days. Adult prophylaxis in colorectal surgery: 1g single IV dose given 1 hour prior to surgical incision.

    Invanz Contraindications

    Contraindications

    Penicillin, cephalosporin, or other β-lactam allergy. IM administration in patients with known hypersensitivity to amide-type local anesthetics.

    Invanz Boxed Warnings

    Not Applicable

    Invanz Warnings/Precautions

    Warnings/Precautions

    CNS disorders (eg, brain lesions, seizure history). Renal dysfunction. Avoid extravasation. Monitor renal, hepatic, and hematopoetic function in prolonged use. Avoid blood vessel if administering by IM. Elderly. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Hypersensitivity Reactions

    • Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. 

    • Prior to initiation, carefully inquire patients regarding previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams and other allergens.

    • Discontinue Invanz immediately if an allergic reaction to Invanz occurs.

    Seizure Potential 

    • Seizures and other central nervous system (CNS) adverse experiences have been reported.  These experiences are more common in patients with CNS disorders (eg, brain lesions or history of seizures) and/or compromised renal function.

    • If focal tremors, myoclonus, or seizures occur, evaluate patients neurologically, place patients on anticonvulsant therapy (if not already instituted), and re-examine Invanz dose.

    Interaction with Valproic Acid

    • Concomitant use of carbapenems (eg, ertapenem) with valproic acid or divalproex sodium is not recommended due to a reduction in valproic acid concentrations, which may increase the risk for breakthrough seizures.

    • If unavoidable and Invanz is necessary, consider supplemental anticonvulsant therapy.

    Clostridioides difficile-Associated Diarrhea (CDAD)

    • If CDAD is suspected or confirmed, ongoing antibiotic use not directed against Clostridioides difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of Clostridioides difficile, and surgical evaluation should be instituted as clinically indicated. 

    Caution with Intramuscular Administration

    • Caution should be taken when administering Invanz intramuscularly to avoid inadvertent injection into a blood vessel. 

    Laboratory Tests

    • Periodically assess organ system function, including renal, hepatic, and hematopoietic, during prolonged therapy. 

    Pregnancy Considerations

    Risk Summary

    • Available data from a small number of post-marketing cases with Invanz use in pregnancy are insufficient to inform any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes.

    Nursing Mother Considerations

    Risk Summary

    • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for Invanz and any potential adverse effects on the breastfed infant from Invanz or from the underlying maternal condition. 

    Pediatric Considerations

    Invanz is not recommended in infants under 3 months of age as no data are available. Invanz is not recommended in the treatment of meningitis in the pediatric population due to lack of sufficient CSF penetration.

    Geriatric Considerations

    Invanz is known to be substantially excreted by the kidney. Carefully select dose in elderly patients because of the increased likelihood of decreased renal function. Monitor renal function in elderly patients.

    Renal Impairment Considerations

    Dosage adjustment is necessary in patients with creatinine clearance 30 mL/min or less.

    Hepatic Impairment Considerations

    The pharmacokinetics of ertapenem in patients with hepatic impairment have not been established.

    Invanz Pharmacokinetics

    Absorption

    Mean bioavailability: ~90%. Mean peak plasma concentrations are achieved in ~2.3 hours.

    Distribution

    ~85 to 95% plasma protein bound. Apparent volume of distribution at steady state: ~0.12 L/kg in adults; ~0.2 L/kg in pediatric patients 3 months to 12 years of age; ~0.16 L/kg in pediatric patients 13 to 17 years of age.

    Metabolism

    Hydrolysis.

    Elimination

    Renal (80%), fecal (10%). Half-life: ~2.5 hours (3months–12yrs); ~4 hours (≥13yrs).

    Invanz Interactions

    Interactions

    Potentiated by probenecid: not recommended. Antagonizes valproic acid or divalproex sodium: not recommended; consider other antibacterials.

    Invanz Adverse Reactions

    Adverse Reactions

    Diarrhea (evaluate if occurs), nausea, vomiting, inj site reactions (thrombophlebitis/phlebitis, pain), headache, CNS effects (dizziness, altered mental state, rarely: seizures), edema, dyspnea, fever.

    Invanz Clinical Trials

    Clinical Trials

    Adult Patients

    Complicated Intra-Abdominal Infections

    • A randomized, double-blind, non-inferiority clinical trial evaluated ertapenem for the treatment of complicated intra-abdominal infections in 655 adults with localized complicated appendicitis, and any other complicated intra-abdominal infection including colonic, small intestinal, and biliary infections and generalized peritonitis. Patients were randomly assigned to receive ertapenem (1 g intravenously once a day) with piperacillin/tazobactam (3.375 g intravenously every 6 hours) for 5 to 14 days.

    • The combined clinical and microbiologic success rates in the microbiologically evaluable population at 4 to 6 weeks post-therapy (test-of-cure) were 83.6% (163/195) for ertapenem and 80.4% (152/189) for piperacillin/tazobactam. 

    Complicated Skin and Skin Structure Infections

    • A randomized, double-blind, non-inferiority clinical trial evaluated ertapenem for the treatment of 540 patients with deep soft tissue abscess, posttraumatic wound infection and cellulitis with purulent drainage. Patients were randomly assigned to receive ertapenem (1 g intravenously once a day) with piperacillin/tazobactam (3.375 g intravenously every 6 hours) for 7 to 14 days. 

    • The clinical success rates at 10 to 21 days post therapy (test-of-cure) were 83.9% (141/168) for ertapenem and 85.3% (145/170) for piperacillin/tazobactam.

    Diabetic Foot Infections

    • A randomized, double-blind, non-inferiority clinical trial evaluated ertapenem for the treatment of diabetic foot infections without concomitant osteomyelitis in 586 adults. Patients were randomly assigned to receive ertapenem (1 g intravenously once a day) with piperacillin/tazobactam (3.375 g intravenously every 6 hours). 

    • The clinical success rates at 10 days post therapy were 75.0% (153/204) for ertapenem and 70.8% (143/202) for piperacillin/tazobactam. 

    Community Acquired Pneumonia

    • Two randomized, double-blind, non-inferiority clinical trials evaluated ertapenem for the treatment of community acquired pneumonia in 866 adults. In both trials, patients were randomly assigned to receive  ertapenem (1 g parenterally once a day) with ceftriaxone (1 g parenterally once a day). Patients were 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 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 post therapy (test-of-cure).

    • In the second trial, 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 post therapy (test-of-cure).  

    Complicated Urinary Tract Infections Including Pyelonephritis

    • Two randomized, double-blind, non-inferiority clinical trials evaluated ertapenem for the treatment of complicated urinary tract infections including pyelonephritis in 850 adults. In both trials, patients were randomly assigned to receive  ertapenem (1 g parenterally once a day) with ceftriaxone (1 g parenterally once a day). Patients were allowed the option to switch to oral amoxicillin/clavulanate for a total of 10 to 14 days of treatment (parenteral and oral).

    • The microbiological success rates (combined trials) at 5 to 9 days post therapy (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

    • A randomized, doubleblind, non-inferiority clinical trial evaluated ertapenem for the treatment of acute pelvic infections in 350 adults. Patients were randomly assigned to receive ertapenem (1 g intravenously once a day) with piperacillin/tazobactam (3.375 g intravenously every 6 hours) for 3 to 10 days.

    • 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 

    • A multicenter, randomized, double-blind, non-inferiority clinical trial evaluated ertapenem in adults for prophylaxis of surgical site infection following elective colorectal surgery. Patients were randomly assigned to receive a single intravenous dose of ertapenem (1 g) versus cefotetan (2 g) administered over 30 minutes, 1 hour before elective colorectal surgery. 

    • The prophylactic success rates at 4 weeks post treatment in the clinically evaluable population were 70.5% (244/346) for ertapenem and 57.2% (194/339) for cefotetan (difference 13.3%, [95% CI: 6.1, 20.4], P <.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.

    • In the MITT analysis, the prophylactic success rates at 4 weeks post treatment were 58.3% (263/451) for ertapenem and 48.9% (220/450) for cefotetan (difference 9.4%, [95% CI: 2.9, 15.9], P =.002).

     

    Pediatric Patients

    Two randomized, multicenter clinical trials evaluated ertapenem in pediatric patients 3 months to 17 years of age.

    • The first trial included 404 patients who were randomly assigned to receive ertapenem (15 mg/kg IV every 12 hours in patients 3 months to 12 years of age, and 1 g IV once a day in patients 13 to 17 years of age) to ceftriaxone (50 mg/kg/day IV in two divided doses in patients 3 months to 12 years of age and 50 mg/kg/day IV as a single daily dose in patients 13 to 17 years of age) for the treatment of complicated urinary tract infection (UTI), skin and soft tissue infection (SSTI), or community-acquired pneumonia (CAP). The microbiological success rates in the evaluable per protocol (EPP) analysis in patients treated for UTI were 87.0% (40/46) for ertapenem and 90.0% (18/20) for ceftriaxone. The clinical success rates in the EPP analysis in patients treated for SSTI were 95.5% (64/67) for ertapenem and 100% (26/26) for ceftriaxone, and in patients treated for CAP were 96.1% (74/77) for ertapenem and 96.4% (27/28) for ceftriaxone.

    • The second trial included 112 patients who were randomly assigned to receive  ertapenem (15 mg/kg IV every 12 hours in patients 3 months to 12 years of age, and 1 g IV once a day in patients 13 to 17 years of age) to ticarcillin/clavulanate (50 mg/kg for patients <60 kg or 3.0 g for patients >60 kg, 4 or 6 times a day) up to 14 days for the treatment of complicated intra-abdominal infections (IAI) and acute pelvic infections (API). The clinical success rates were 83.7% (36/43) for ertapenem and 63.6% (7/11) for ticarcillin/clavulanate in the EPP analysis for patients treated for IAI. The clinical success rates were 100% (23/23) for ertapenem and 100% (4/4) for ticarcillin/clavulanate in the EPP analysis for patients treated for API.

    Invanz Note

    Notes

    For IM use, reconstitute with lidocaine 1% only; see full labeling.

    Invanz Patient Counseling

    See Literature

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