Invanz

Carbapenems

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Ertapenem solution is colorless to pale yellow; variations of color within this range do not affect the potency of the product.

Intravenous (IV) Infusion
Powder Vials for Injection
Reconstitution
Reconstitute each 1 g vial with 10 mL of 0.9% Sodium Chloride Injection, Sterile Water for Injection, or Bacteriostatic Water for Injection using a syringe equipped with a 21-gauge or smaller diameter needle. Use with a needless IV system is not recommended.[30920] According to the manufacturer, the final concentration after reconstitution is 100 mg/mL.[41532]
Shake well to dissolve.
Further dilution is necessary for IV infusion.
Storage: Immediately transfer the appropriate amount of the reconstituted vial to diluent. Discard vial with unused portion of the reconstituted solution.[30920]
 
Dilution
For a 1 g dose: further dilute with 50 mL of 0.9% Sodium Chloride Injection.
For a dose less than 1 g: further dilute the appropriate dose with 0.9% Sodium Chloride Injection to a concentration of 20 mg/mL or less.
Storage: Use within 6 hours if stored at room temperature (25 degrees C). The diluted solution may be refrigerated for up to 24 hours (5 degrees C) and used within 4 hours after removal from refrigeration. Do not freeze.[30920]
 
Intermittent IV Infusion
Complete the infusion within 6 hours of reconstitution.
Infuse IV over 30 minutes.
Do not co-infuse with other medications.[30920]
 
Intravenous (IV) Push†
NOTE: Ertapenem is not approved by the FDA for IV push administration.
Powder Vials for Injection
Reconstitution
A study included 12 healthy adult volunteers who received ertapenem by IV push.
Doses of 1 g were reconstituted with 0.9% Sodium Chloride Injection to a total volume of 10 mL (100 mg/mL).
Stability:
In the 12-person volunteer study, doses (100 mg/mL) were stored under refrigeration and used within 6 hours of preparation; stability was not assessed.
In a stability study, ertapenem reconstituted in 0.9% Sodium Chloride Injection to a total volume of 10 mL (100 mg/mL) and stored in polypropylene syringes was stable for 30 minutes at room temperature (25 degrees C), for 24 hours under refrigeration (4 degrees C) followed by 4 hours at room temperature (25 degrees C), for 14 days frozen (-20 degrees C) followed by 5 hours at room temperature (25 degrees C), and for 28 days frozen (-20 degrees C) followed by 3 hours at room temperature (25 degrees C).
 
Intermittent IV Push
Doses were administered IVP at a rate of 5 minutes in 12 healthy adult volunteers.

Reconstitution
Reconstitute the 1 g vial with 3.2 mL of 1% lidocaine injection (without epinephrine) to a final concentration of approximately 280 mg/mL.
Agitate well to form a solution.
Storage: Use within 1 hour after preparation. Discard vial with unused portion of the reconstituted solution.[30920]
 
Intramuscular Injection
The IM reconstituted formulation is not for IV use.
IM administration may be used as an alternative to IV administration in the treatment of infections where IM therapy is appropriate; however, only administer via IM injection for 7 days.
Immediately withdraw the appropriate dose and inject deeply into a large muscle (i.e., upper outer quadrant of the gluteus maximus or lateral part of the thigh).
Storage: Use within 1 hour after preparation.[30920]

GI obstruction / Delayed / 2.1-2.1
seizures / Delayed / 0.5-0.5
ileus / Delayed / 0.1
GI bleeding / Delayed / 0.1
pyloric stenosis / Delayed / 0.1
pancreatitis / Delayed / 0.1
atrial fibrillation / Early / 0.1
cardiac arrest / Early / 0.1
asystole / Rapid / 0.1
bradycardia / Rapid / 0.1
heart failure / Delayed / 0.1
ventricular tachycardia / Early / 0.1
stroke / Early / 0.5
pleural effusion / Delayed / 0.1
pulmonary embolism / Delayed / 0.5
oliguria / Early / 0.1
azotemia / Delayed / 0.1
anuria / Delayed / 0.1
angioedema / Rapid / 0.1
wound dehiscence / Delayed / 0.5
hyperkalemia / Delayed / 0.1
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
C. difficile-associated diarrhea / Delayed / Incidence not known

elevated hepatic enzymes / Delayed / 0.6-8.8
anemia / Delayed / 5.7-5.7
confusion / Early / 3.3-5.1
constipation / Delayed / 2.3-4.0
edema / Delayed / 2.9-3.4
vaginitis / Delayed / 1.4-3.3
dyspnea / Early / 1.0-2.6
hypotension / Rapid / 1.0-2.0
erythema / Early / 0.1
phlebitis / Rapid / 0.1
jaundice / Delayed / 0.1
hyperbilirubinemia / Delayed / 0.1
cholelithiasis / Delayed / 0.1
esophagitis / Delayed / 0.1
dysphagia / Delayed / 0.1
hemorrhoids / Delayed / 0.1
stomatitis / Delayed / 0.1
gastritis / Delayed / 0.1
oral ulceration / Delayed / 0.1
hypertension / Early / 0.1
sinus tachycardia / Rapid / 0.1
hematoma / Early / 0.1
chest pain (unspecified) / Early / 0.1
depression / Delayed / 0.1
hemoptysis / Delayed / 0.1
wheezing / Rapid / 0.5
dysuria / Early / 0.5
urinary retention / Early / 0.1
hematuria / Delayed / 0.1
pseudomembranous colitis / Delayed / 0.1
candidiasis / Delayed / 0.1
bleeding / Early / 0.5
flank pain / Delayed / 0.1
gout / Delayed / 0.1
hyperglycemia / Delayed / 0.1
hypokalemia / Delayed / 0.1
hypernatremia / Delayed / 0.1
encephalopathy / Delayed / Incidence not known
myoclonia / Delayed / Incidence not known
delirium / Early / Incidence not known
dyskinesia / Delayed / Incidence not known
hallucinations / Early / Incidence not known
superinfection / Delayed / Incidence not known

diarrhea / Early / 5.5-11.7
vomiting / Early / 2.1-10.2
nausea / Early / 0.6-8.5
injection site reaction / Rapid / 0.2-7.1
headache / Early / 2.2-6.8
infection / Delayed / 0.6-6.5
agitation / Early / 3.3-5.1
drowsiness / Early / 0.6-5.1
fever / Early / 2.3-5.0
abdominal pain / Early / 0.6-4.7
cough / Delayed / 0.2-4.4
insomnia / Early / 0.6-3.2
rash / Early / 2.3-2.9
dizziness / Early / 0.6-2.1
pruritus / Rapid / 0.6-2.0
flushing / Rapid / 0.1
hyperhidrosis / Delayed / 0.1
urticaria / Rapid / 0.1
anorexia / Delayed / 0.1
flatulence / Early / 0.1
weight loss / Delayed / 0.1
dyspepsia / Early / 0.1
dysgeusia / Early / 0.1
xerostomia / Early / 0.5
anxiety / Delayed / 0.1
tremor / Early / 0.1
syncope / Early / 0.1
vertigo / Early / 0.1
asthenia / Delayed / 0.1
fatigue / Early / 0.1
hypoesthesia / Delayed / 0.1
paresthesias / Delayed / 0.1
hiccups / Early / 0.1
rhinitis / Early / 0.5
pharyngitis / Delayed / 0.1
rhinorrhea / Early / 0.5
epistaxis / Delayed / 0.1
increased urinary frequency / Early / 0.5
malaise / Early / 0.1
hypothermia / Delayed / 0.5
chills / Rapid / 0.1
muscle cramps / Delayed / 0.5
arthralgia / Delayed / 0.5
tooth discoloration / Delayed / Incidence not known

Invanz

Rx

IV or IM broad-spectrum carbapenem antibiotic stable against beta-lactamases
Used to treat UTI, skin, pelvic, intraabdominal infections and community-acquired pneumonia; used for colorectal surgical prophylaxis
Once-daily dosing may be advantageous, but no P. aeruginosa activity 

1 g IV or IM once daily for 10 to 14 days. Consider transitioning to an appropriate oral therapy after at least 3 days of parenteral therapy, once clinical improvement has been demonstrated.[30920]

1 g IV or IM once daily for 10 to 14 days. Consider transitioning to an appropriate oral therapy after at least 3 days of parenteral therapy, once clinical improvement has been demonstrated.

15 mg/kg/dose IV or IM twice daily (Max: 1 g/day) for 10 to 14 days. Consider transitioning to an appropriate oral therapy after at least 3 days of parenteral therapy, once clinical improvement has been demonstrated.

15 mg/kg/dose IV or IM twice daily.

1 g IV every 24 hours for incisional surgical site infections of the intestinal or genitourinary tract.

1 g IV every 24 hours.

1 g IV every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for mixed necrotizing infections.

1 g IV every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for mixed necrotizing infections.

15 mg/kg/dose (Max: 1 g/dose) IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for mixed necrotizing infections.

15 mg/kg/dose IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for mixed necrotizing infections.

1 g IV or IM every 24 hours for 7 to 14 days.

1 g IV or IM every 24 hours for 7 to 14 days.

15 mg/kg/dose (Max: 1 g/dose) IV or IM every 12 hours for 7 to 14 days.

15 mg/kg/dose IV or IM every 12 hours for 7 to 14 days.

1 g IV every 24 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.

1 g IV every 24 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.

15 mg/kg/dose (Max: 1 g/dose) IV every 12 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.

15 mg/kg/dose IV every 12 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.

1 g IV or IM every 24 hours for 7 to 14 days for moderate or severe infections in patients with recent antibiotic exposure or infections with ischemic limb/necrosis/gas forming. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.

1 g IV or IM once daily for 3 to 10 days.

1 g IV or IM once daily for 3 to 10 days.

15 mg/kg/dose IV or IM twice daily (Max: 1 g/day) for 3 to 10 days.

1 g IV as a single dose within 60 minutes prior to the surgical incision. No intraoperative redosing is necessary. The duration of prophylaxis should not exceed 24 hours.

15 mg/kg/dose IV as a single dose (Max: 1 g/dose) within 60 minutes prior to the surgical incision. No intraoperative redosing is necessary. The duration of prophylaxis should not exceed 24 hours.

1 g IV or IM once daily for 5 to 14 days.

1 g IV or IM once daily for 5 to 14 days.

15 mg/kg/dose IV or IM every 12 hours (Max: 1 g/day) for 5 to 14 days.

15 mg/kg/dose IV or IM twice daily. FDA-labeling for other populations suggests a duration of 5 to 14 days.

1 g IV every 24 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

1 g IV every 24 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

15 mg/kg/dose IV every 12 hours (Max: 1 g/day) for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

15 mg/kg/dose IV every 12 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

1 g IV once as a single dose as antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

1 g IV as a single dose as antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

15 mg/kg/dose IV every 12 hours (Max: 1 g/day). Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

500 mg IV every 24 hours for 21 days.

1 g IV every 24 hours for at least 48 hours, followed by oral step-down therapy for a total treatment duration of 5 to 10 days. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

1 g IV every 24 hours for at least 48 hours, followed by oral step-down therapy for a total treatment duration of 5 to 10 days. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

15 mg/kg/dose IV every 12 hours (Max: 1 g/day) for at least 48 hours, followed by oral step-down therapy for a total treatment duration of 5 to 10 days. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

1 g IV or IM once daily for 7 to 14 days.

1 g IV or IM once daily for 10 to 14 days.

15 mg/kg/dose IV or IM twice daily (Max: 1 g/day) for 10 to 14 days.

15 mg/kg/dose IV or IM twice daily.

1 g IV once daily for 3 to 7 days.

1 g IV once daily for 7 to 14 days.

1 g IV every 24 hours for 10 to 14 days. Consider adding azithromycin for patients who do not improve.

1 g IV every 24 hours for 6 weeks as first-line therapy for infections due to Enterobacterales.

1 g IV every 24 hours for 4 to 6 weeks as first-line therapy for infections due to Enterobacterales, which may be followed by chronic oral suppressive therapy.

1 g IV as a single dose as an alternative.

1 g IV as a single dose as an alternative.

15 mg/kg/dose (Max: 1 g/dose) IV as a single dose as an alternative.

1 g IV every 24 hours during the intrapartum period as an alternative. Give 1 additional dose after cesarean delivery; an additional dose is generally not needed after vaginal delivery. Other risk factors such as bacteremia or persistent postpartum fever may require additional therapy.

1 g IV every 24 hours during the intrapartum period as an alternative. Give 1 additional dose after cesarean delivery; an additional dose is generally not needed after vaginal delivery. Other risk factors such as bacteremia or persistent postpartum fever may require additional therapy.

†Indicates off-label use

No dosage guidelines are available; it appears no dosage adjustment is needed.

No data are available regarding use in pediatric patients with renal impairment.
FDA-approved dosage in renal failure for adults:
CrCl > 30 mL/min: No dosage adjustment needed.
CrCl <= 30 mL/min: 500 mg IV or IM once a day.
 
Other dosage adjustment guidelines for adults:
CrCl > 10 mL/min: No dosage adjustment needed.
CrCl < 10 mL/min: 500 mg IV or IM once a day.
 
Intermittent hemodialysis
Give recommended dose of 500 mg IV or IM once a day. If ertapenem is given 6 hours or more prior to hemodialysis, no supplemental dosing is required. If ertapenem is given within 6 hours of hemodialysis, a supplementary dose of 150 mg is recommended following the hemodialysis session.
 
Peritoneal dialysis
Administer 500 mg IV or IM once a day.
 
Continuous renal replacement therapy (CRRT)
No dosage adjustment is necessary unless anticipated clearance is < 30 mL/min.

Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Probenecid: (Minor) Probenecid inhibits the renal excretion of ertapenem by competing with them for active tubular secretion. In some instances, this effect is used therapeutically to increase availability of the antimicrobial agent. However, the elimination half-life of ertapenem is increased only from 4 to 4.8 hours. Concurrent administration of ertapenem with probenecid is not recommended.
Probenecid; Colchicine: (Minor) Probenecid inhibits the renal excretion of ertapenem by competing with them for active tubular secretion. In some instances, this effect is used therapeutically to increase availability of the antimicrobial agent. However, the elimination half-life of ertapenem is increased only from 4 to 4.8 hours. Concurrent administration of ertapenem with probenecid is not recommended.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Valproic Acid, Divalproex Sodium: (Major) Avoid concomitant carbapenem and valproic acid use. Consider alternative antibacterial therapies other than carbapenems to treat infections in patients whose seizures are well controlled with valproic acid or divalproex sodium. If coadministered, monitor valproic acid concentrations. Coadministration of carbapenems with valproic acid or divalproex sodium may reduce the serum concentration of valproic acid potentially increasing the risk of breakthrough seizures. Carbapenems may inhibit the hydrolysis of valproic acid's glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing valproic acid serum concentrations.
Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including carbapenems, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.

Ertapenem/Invanz Intramuscular Inj Pwd F/Sol: 1g
Ertapenem/Invanz Intravenous Inj Pwd F/Sol: 1g

1 g/day IV/IM.

1 g/day IV/IM.

1 g/day IV/IM.

30 mg/kg/day IV/IM (Max: 1 g/day).

3 to 11 months: 30 mg/kg/day IV/IM.
1 to 2 months: Safety and efficacy have not been established; however, doses up to 30 mg/kg/day IV/IM are recommended off-label.

Safety and efficacy have not been established.

Ertapenem exhibits bactericidal activity due inhibition of cell wall synthesis mediated via binding to penicillin binding proteins (PBPs). It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific PBPs that are located inside the bacterial cell wall. PBPs are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. PBPs vary among different bacterial species. In E. coli, ertapenem has shown strong affinity towards PBPs 1a, 1b, 2, 3, 4 and 5 with preference for PBPs 2 and 3. PBP-1 is responsible for formation of the cell wall; PBP-2 is responsible for maintaining the rod-like shape, and PBP-3 is responsible for bacterial septum formation. Ertapenem is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases. Like meropenem, but unlike imipenem, it has a 1-beta-methyl substituent and does not require protection with an inhibitor of human renal dihydropeptidase I.[26787] [30920] [50330]
 
Beta-lactams, including ertapenem, exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism (free T above the MIC).[34145] [34143] [35436] [35437] [35438] [35439] This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase.[35439] Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval. The percentage of time required for both bacteriostatic and maximal bactericidal activity is different for the various classes of beta-lactams. Carbapenems require free drug concentrations to exceed the MIC for 20% of the dosing interval for bacteriostatic activity and 40% of the dosing interval for maximal bactericidal activity.[35436] [35437] [35438] Carbapenems also are reported to have a post-antibiotic effect (PAE). PAE is defined as the suppression of bacterial growth that continues after the antibiotic concentration falls below the bacterial MIC. Ertapenem has a short PAE of 1.4 to 2.6 hours against gram-positive strains only.[26788] [35441]
 
The susceptibility interpretive criteria for ertapenem are delineated by pathogen. The MICs are defined for Enterobacterales as susceptible at 0.5 mcg/mL or less, intermediate at 1 mcg/mL, and resistant at 2 mcg/mL or more. The MICs are defined for S. pneumoniae as susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more. The MICs are defined for Staphylococcus sp. as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more. The MICs are defined for beta-hemolytic group Streptococcus sp. and Viridans group Streptococcus sp. as susceptible at 1 mcg/mL or less. The MICs are defined for H. influenzae and H. parainfluenzae as susceptible at 0.5 mcg/mL or less. The MICs are defined for anaerobes as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more.[63320] [63321]
 
There are 4 general mechanisms of carbapenem resistance including decreased permeability of the outer membrane of gram-negative organisms due to decreased porin channel production, decreased affinity for the target PBPs, over-expression of efflux pumps, and enzymatic degradation.[28347] Generally, carbapenems show stability to the majority of beta-lactamases, including AmpC beta-lactamases and extended-spectrum beta-lactamases (ESBLs). However, specific intrinsic or acquired beta-lactamases, generally called carbapenemases, can hydrolyze the carbapenems. These include some class A enzymes, several class D (OXA) enzymes, and the class B metallo-beta-lactamases.[28347] [35440] [35441] A deficiency in the outer membrane porin protein (Opr) D2 is associated with decreased carbapenem susceptibility in gram-negative bacteria. However, it is theorized that a combination of resistance mechanisms is required for significant carbapenem resistance. Theoretically, efflux activity plus loss of membrane permeability is less likely to happen in vivo than AmpC beta-lactamase expression and loss of membrane permeability.[35440] [35441]

Ertapenem is administered via intravenous (IV) or intramuscular (IM) routes. Ertapenem exhibits non-linear pharmacokinetics due to a high level of concentration-dependent plasma protein binding to albumin. Protein binding averages 95% at an approximate plasma concentration of less than 100 mcg/mL and decreases to approximately 85% at a plasma concentration of 300 mcg/mL.[30920] However, protein binding is not deleterious to ertapenem's in-vivo efficacy against organisms for which the MICs are low.[26791] Ertapenem distributes into human breast milk and crosses the rat placental barrier. Activity is maintained by the parent drug until the beta-lactam ring is hydrolyzed resulting in an inactive metabolite. Ertapenem is not a substrate for P-glycoprotein-mediated transport. It is eliminated via the kidney. Approximately 80% is recovered in the urine, roughly 38% as unchanged drug and 37% as the inactive metabolite; 10% is recovered in the feces. The elimination half-life of ertapenem in healthy young adults in approximately 4 hours.[30920]
 
Affected cytochrome P450 isoenzymes: none
In vitro studies have shown that ertapenem does not inhibit metabolism mediated by cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4. In vitro studies have also shown that it does not inhibit P-glycoprotein-mediated transport of digoxin or vinblastine.[30920]

Accumulation of ertapenem does not occur following multiple IV doses in healthy adults.

Absorption of ertapenem is almost complete following IM administration with mean bioavailability of 90%. Peak plasma concentrations following a 1 g dose are achieved in roughly 2.3 hours. Accumulation does not occur following multiple IM doses in healthy adults.

Available data from a small number of postmarketing cases with ertapenem use in pregnancy are insufficient to inform any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies evaluating doses 1.2 and 3 times the recommended human dose of 1 g, there was no evidence of fetal developmental toxicity; however, slight decreases in fetal weights and numbers of ossified sacrocaudal vertebrae were observed.

Ertapenem is excreted in human breast milk. The concentration in breast milk 24 hours after a 1 g dose ranged from less than 0.13 mcg/mL (lower limit of quantitation) to 0.38 mcg/mL in 5 lactating women. By day 5 after discontinuation, the concentration in breast milk was undetectable. There are no data on the effects of ertapenem on the breast-fed infant or on milk production. In general, unless the infant is allergic to ertapenem, breast-feeding is likely safe during maternal carbapenem therapy; observe the infant for potential effects. Consider the benefits of breast-feeding along with the mother's clinical need for ertapenem and any potential adverse effects on the breast-fed infant from ertapenem or the underlying maternal condition.