Stability data:
|
| Drug |
Stability
Refrigerated |
Stability
Room Temp. |
Reconstituted
Vial/Powder |
Notes |
| Ertapenem |
24 hours under refrigeration (5°C) and used within 4 hours after removal from refrigeration. Solutions of INVANZ should not be frozen. |
6 hours at room temperature (25°C) |
Powder |
|
Label: Refrigerate.
| Microbiology (see below).
Notes: (limitations)
-Doripenem, imipenem, and meropenem cover most strains of P aeruginosa and Acinetobacter species. However ertapenem lacks sufficient activity.
-Ertapenem is not indicated for enterococcal infections (lacks activity). |
Preparation:
(IV): Reconstitute 1 gram vial with 10 mL of Water for Injection, 0.9% Sodium Chloride Injection, or Bacteriostatic Water for Injection and then add contents to 50 ml normal saline. Complete the infusion within 6 hours of reconstitution.
(IM): Reconstitute 1 gram vial with 3.2 mL of lidocaine 1% injection without epinephrine. Give deep IM into a large muscle mass (gluteal or lateral aspect of thigh). Administer solution within 1 hour of preparation. DO NOT give this solution Intravenously
INDICATIONS AND USAGE
Treatment
INVANZ is indicated for the treatment of patients with the following moderate to severe infections caused by susceptible isolates of the designated microorganisms.
Complicated Intra-abdominal Infections due to Escherichia coli, Clostridium clostridioforme, Eubacterium lentum, Peptostreptococcus species, Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, or Bacteroides uniformis.
Complicated Skin and Skin Structure Infections, including diabetic foot infections without osteomyelitis due to Staphylococcus aureus (methicillin susceptible isolates only), Streptococcus agalactiae, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Bacteroides fragilis, Peptostreptococcus species, Porphyromonas asaccharolytica, or Prevotella bivia. INVANZ has not been studied in diabetic foot infections with concomitant osteomyelitis.
Community Acquired Pneumonia due to Streptococcus pneumoniae (penicillin susceptible isolates only) including cases with concurrent bacteremia, Haemophilus influenzae (beta-lactamase negative isolates only), or Moraxella catarrhalis.
Complicated Urinary Tract Infections including pyelonephritis due to Escherichia coli, including cases with concurrent bacteremia, or Klebsiella pneumoniae.
Acute Pelvic Infections including postpartum endomyometritis, septic abortion and post surgical gynecologic infections due to Streptococcus agalactiae, Escherichia coli, Bacteroides fragilis, Porphyromonas asaccharolytica, Peptostreptococcus species, or Prevotella bivia.
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.
Mechanism of 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.
Coverage:
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.
DOSAGE AND ADMINISTRATION
The dose of INVANZ in patients 13 years of age and older is 1 gram (g) given once a day. The dose of INVANZ in patients 3 months to 12 years of age is 15 mg/kg twice daily (not to exceed 1 g/day). INVANZ may be administered by intravenous infusion for up to 14 days or intramuscular injection for up to 7 days. When administered intravenously, INVANZ should be infused over a period of 30 minutes.
Intramuscular administration of INVANZ may be used as an alternative to intravenous administration in the treatment of those infections for which intramuscular therapy is appropriate.
DO NOT MIX OR CO-INFUSE INVANZ WITH OTHER MEDICATIONS. DO NOT USE DILUENTS CONTAINING DEXTROSE (a-D-GLUCOSE).
Treatment Guidelines for Adults and Pediatric Patients With Normal Renal Function (creatinine clearance >90 mL/min/1.73 m2) and Body Weight
| Infection |
Daily Dose
(IV or IM)
Adults and Pediatric Patients 13 years of age and older |
Daily Dose
(IV or IM)
Pediatric Patients 3 months to 12 years of age |
Recommended Duration of Total Antimicrobial Treatment |
| Complicated intra-abdominal infections |
1 g |
15 mg/kg
twice daily (not to exceed 1 g/day) |
5 to 14 days |
| Complicated skin and skin structure infections, including diabetic foot infections |
1 g |
15 mg/kg
twice daily (not to exceed 1 g/day) |
7 to 14 days (adult patients with diabetic foot infections received up to 28 days of treatment (parenteral or parenteral plus oral switch therapy)) |
| Community acquired pneumonia |
1 g |
15 mg/kg
twice daily (not to exceed 1 g/day) |
10 to 14 days (duration includes a possible switch to an appropriate oral therapy, after at least 3 days of parenteral therapy, once clinical improvement has been demonstrated.) |
| Complicated urinary tract infections, including pyelonephritis |
1 g |
15 mg/kg
twice daily (not to exceed 1 g/day) |
10 to 14 days (duration includes a possible switch to an appropriate oral therapy, after at least 3 days of parenteral therapy, once clinical improvement has been demonstrated.) |
| Acute pelvic infections including postpartum endomyometritis, septic abortion and post surgical gynecologic infections |
1 g |
15 mg/kg
twice daily (not to exceed 1 g/day) |
3 to 10 days |
Prophylaxis Guidelines for Adults
| Indication |
Daily Dose(IV) Adults |
Recommended Duration of Total Antimicrobial Treatment |
| Prophylaxis of surgical site infection following elective colorectal surgery |
1 g |
Single intravenous dose given 1 hour prior to surgical incision |
Patients with Renal Insufficiency: ---------------------------
INVANZ may be used for the treatment of infections in adult patients with renal insufficiency. In patients whose creatinine clearance is >30 mL/min/1.73 m2, no dosage adjustment is necessary. Adult patients with advanced renal insufficiency (creatinine clearance ≤30 mL/min/1.73 m2) and end-stage renal insufficiency (creatinine clearance ≤10 mL/min/1.73 m2) should receive 500 mg daily. There are no data in pediatric patients with renal insufficiency.
Patients on Hemodialysis: When adult patients on hemodialysis are given the recommended daily dose of 500 mg of INVANZ within 6 hours prior to hemodialysis, a supplementary dose of 150 mg is recommended following the hemodialysis session. If INVANZ is given at least 6 hours prior to hemodialysis, no supplementary dose is needed. There are no data in patients undergoing peritoneal dialysis or hemofiltration. There are no data in pediatric patients on hemodialysis.
When only the serum creatinine is available, the following formula2 may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function.
Males: (weight in kg) x (140-age in years) / [(72) x serum creatinine (mg/100 mL)]
Females: (0.85) x (value calculated for males)
Patients with Hepatic Insufficiency: No dose adjustment recommendations can be made in patients with impaired hepatic function.
PREPARATION OF SOLUTION----------------------------------------------------
Vials
Adults and pediatric patients 13 years of age and older
Preparation for intravenous administration:
DO NOT MIX OR CO-INFUSE INVANZ WITH OTHER MEDICATIONS. DO NOT USE DILUENTS CONTAINING DEXTROSE (a-D-GLUCOSE).
INVANZ MUST BE RECONSTITUTED AND THEN DILUTED PRIOR TO ADMINISTRATION.
1. Reconstitute the contents of a 1 g vial of INVANZ with 10 mL of one of the following: Water for Injection, 0.9% Sodium Chloride Injection or Bacteriostatic Water for Injection.
2. Shake well to dissolve and immediately transfer contents of the reconstituted vial to 50 mL of 0.9% Sodium Chloride Injection.
3. Complete the infusion within 6 hours of reconstitution.
Preparation for intramuscular administration:
INVANZ MUST BE RECONSTITUTED PRIOR TO ADMINISTRATION.
1. Reconstitute the contents of a 1 g vial of INVANZ with 3.2 mL of 1.0% lidocaine HCl injection* (without epinephrine). Shake vial thoroughly to form solution.
2. Immediately withdraw the contents of the vial and administer by deep intramuscular injection into a large muscle mass (such as the gluteal muscles or lateral part of the thigh).
3. The reconstituted IM solution should be used within 1 hour after preparation. NOTE: THE RECONSTITUTED SOLUTION SHOULD NOT BE ADMINISTERED INTRAVENOUSLY.
*Refer to the prescribing information for lidocaine HCl.
--------------------------------------------------------------------------------
Pediatric patients 3 months to 12 years of age:
Preparation for intravenous administration:
DO NOT MIX OR CO-INFUSE INVANZ WITH OTHER MEDICATIONS. DO NOT USE DILUENTS CONTAINING DEXTROSE (a-D-GLUCOSE).
INVANZ MUST BE RECONSTITUTED AND THEN DILUTED PRIOR TO ADMINISTRATION.
1. Reconstitute the contents of a 1 g vial of INVANZ with 10 mL of one of the following: Water for Injection, 0.9% Sodium Chloride Injection or Bacteriostatic Water for Injection.
2. Shake well to dissolve and immediately withdraw a volume equal to 15 mg/kg of body weight (not to exceed 1 g/day) and dilute in 0.9% Sodium Chloride Injection to a final concentration of 20 mg/mL or less.
3. Complete the infusion within 6 hours of reconstitution.
Preparation for intramuscular administration:
INVANZ MUST BE RECONSTITUTED PRIOR TO ADMINISTRATION.
1. Reconstitute the contents of a 1 g vial of INVANZ with 3.2 mL of 1.0% lidocaine HCl injection3 (without epinephrine). Shake vial thoroughly to form solution.
2. Immediately withdraw a volume equal to 15 mg/kg of body weight (not to exceed 1 g/day) and administer by deep intramuscular injection into a large muscle mass (such as the gluteal muscles or lateral part of the thigh).
3. The reconstituted IM solution should be used within 1 hour after preparation. NOTE: THE RECONSTITUTED SOLUTION SHOULD NOT BE ADMINISTERED INTRAVENOUSLY.
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ADD-Vantage®4 Vials
See separate INSTRUCTIONS FOR USE OF INVANZ (Ertapenem for Injection) IN ADD-Vantage® VIALS. INVANZ in ADD-Vantage® vials should be reconstituted with ADD-Vantage® diluent containers containing 50 mL or 100 mL of 0.9% Sodium Chloride Injection.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to use, whenever solution and container permit. Solutions of INVANZ range from colorless to pale yellow. Variations of color within this range do not affect the potency of the product.
Registered trademark of Hospira Laboratories, Inc
STORAGE AND STABILITY
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, PREPARATION OF SOLUTION) 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.
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:
No. 3843—1 g ertapenem equivalent
NDC 0006-3843-71 in trays of 10 vials
INVANZ is supplied as a sterile lyophilized powder in single dose ADD-Vantage® vials containing ertapenem for intravenous infusion as follows:
No. 3845—1 g ertapenem equivalent
NDC 0006-3845-71 in trays of 10 ADD-Vantage® vials.
Manuf for: Merck & Co., Inc., Whitehouse Station, NJ 08889, USA
By: Laboratories Merck Sharp & Dohme-Chibret
63963 Clermont-Ferrand Cedex 9, France
US Patent Nos.: 5,478,820; 5,952,323; 5,652,233
Issued February 2008
Source: [package insert]
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