Ertapenem

Ertapenem belongs to the pharmacological class of Carbapenem antibiotics.

Ertapenem has been approved to relieve symptoms and also for the treatment and maintenance of Bite wound infection, treatment, Bloodstream infection, Diabetic foot infection, moderate to severe, Intra-abdominal infection, mild to moderate, community-acquired in patients without risk factors for resistance or treatment failure, osteomyelitis and/or discitis, Pelvic infection, acute, Pneumonia, Prosthetic joint infection, skin, and soft tissue infection, moderate to severe, Surgical prophylaxis, Urinary tract infection, complicated.

Ertapenem is a long-acting carbapenem antibiotic that exhibits time-dependent bactericidal activity. After intravenous administration, it rapidly distributes into the extracellular fluid and exhibits low protein binding. The kidneys primarily eliminate Ertapenem through glomerular filtration and tubular secretion. Its half-life in healthy individuals is approximately 4 hours, but it can be prolonged in patients with impaired renal function. Ertapenem does not require dosage adjustment in patients with hepatic impairment or elderly patients.

The common side effects involved in using Ertapenem are Diarrhea, Nausea, Vomiting, Abdominal pain, Headache, Dizziness, Rash, and Itching.

Ertapenem is available in the form of Powder for Injection.

Ertapenem is approved in Germany, Japan, Malaysia, India, the U.K., the U.S, and China.

Ertapenem belongs to the pharmacological class of Carbapenem antibiotics.

Ertapenem functions as a bactericidal agent by binding to bacterial penicillin-binding proteins (PBPs) and inhibiting their activity. It displays a strong affinity for several PBPs in Escherichia coli, including PBPs 1a, 1b, 2, 3, 4, and 5, with PBPs 2 and 3 being the most preferred. This binding to PBPs leads to the inhibition of bacterial cell wall synthesis, interfering with the lengthening and strengthening of the peptidoglycan section of the cell wall, ultimately leading to the inhibition of cell wall synthesis.

Ertapenem has been approved to relieve symptoms and also for the treatment and maintenance of Bite wound infection, treatment, Bloodstream infection, Diabetic foot infection, moderate to severe, Intra-abdominal infection, mild to moderate, community-acquired in patients without risk factors for resistance or treatment failure, osteomyelitis and/or discitis, Pelvic infection, acute, Pneumonia, Prosthetic joint infection, skin, and soft tissue infection, moderate to severe, Surgical prophylaxis, Urinary tract infection, complicated.

The Cmax (peak plasma concentration) of ertapenem is achieved approximately 2 hours after intravenous (IV) administration. The Tmax (time to reach Cmax) is also approximately 2 hours after IV administration. The onset of action is rapid, with bacterial growth inhibition occurring within a few hours after administration. The duration of action of ertapenem is approximately 24 hours, allowing for once-daily dosing.

Ertapenem is found to be available in the form of Powder for Injection.

Ertapenem can be used in the following treatment:

• Bite wound infection, treatment
• Bloodstream infection
• Diabetic foot infection, moderate to severe
• Intra-abdominal infection, mild to moderate, community-acquired in patients without risk factors for the resistance or treatment failure.
• Osteomyelitis and/or discitis
• Pelvic infection, acute
• Pneumonia
• Prosthetic joint infection
• Skin and soft tissue infection
• Surgical prophylaxis
• Urinary tract infection, complicated

Ertapenem can help to relieve symptoms and also for the treatment and maintenance of Bite wound infection, treatment, Bloodstream infection, Diabetic foot infection, moderate to severe, Intra-abdominal infection, mild to moderate, community-acquired in patients without risk factors for the resistance or treatment failure, osteomyelitis and/or discitis, Pelvic infection, acute, Pneumonia, Prosthetic joint infection, skin, and soft tissue infection, moderate to severe, Surgical prophylaxis, Urinary tract infection, complicated.

Ertapenem is approved for use in the following clinical indications:

• Bite wound infection, treatment
• Bloodstream infection
• Diabetic foot infection, moderate to severe
• Intra-abdominal infection, mild to moderate, community-acquired in patients without risk factors for the resistance or treatment failure
• Osteomyelitis and/or discitis
• Pelvic infection, acute
• Pneumonia
• Prosthetic joint infection
• Skin and soft tissue infection
• Surgical prophylaxis
• Urinary tract infection, complicated

For Community-Acquired Pneumonia, the recommended dosage for adults is one g/day IV/IM for up to 14 days. After at least three days of parenteral therapy, the patient may be switched to an appropriate PO regimen if there is clinical improvement.

For Complicated Urinary Tract Infections (Including Pyelonephritis), the recommended dosage for adults is one g/day IV/IM for up to 14 days. After at least three days of parenteral therapy, the patient may be switched to an appropriate PO regimen if there is clinical improvement.

For Acute Pelvic Infections, the recommended dosage for adults is one g/day IV/IM for 3-10 days.

For Complicated Intra-abdominal Infections, the recommended dosage for adults is one g/day IV/IM for 5-14 days.

For Complicated Skin/Skin Structure Infections, the recommended dosage for adults is one g/day IV/IM for 7-14 days. For diabetic foot infections, treatment may be continued for up to 4 weeks, depending on the severity of the infection and response to therapy. However, this treatment does not include diabetic foot infections with osteomyelitis.

Powder for injection: 1g/vial

Powder for Injection.

• Dosage Adjustments in Kidney Patients:

If the creatinine clearance (CrCl) is greater than 30 mL/min/1.73 m², no dosage adjustment is required for ertapenem. For patients with CrCl less than 30 mL/min/1.73 m² and end-stage renal disease (ESRD), the recommended dosage of ertapenem is 500 mg per day administered intravenously. In patients receiving dialysis, the recommended dosage is 500 mg per day administered intravenously, if ertapenem is given less than or equal to 6 hours before dialysis, a supplemental dose of 150 mg should be given after dialysis.

• Dosage Adjustments in Hepatic Impairment Patients:

No dosage adjustments are needed for hepatic impairment.

• Dosage Adjustments in Pediatric Patients:

For community-acquired pneumonia, the dosage varies based on age. For patients below three months, the safety and efficacy of ertapenem are not established. For patients between three months to 12 years, the dosage is 15 mg/kg IV/IM every 12 hours for up to 14 days. The maximum dose should not exceed 1 g q12hr. After at least three days of parenteral therapy, patients may switch to an appropriate PO regimen if they improve clinically. For patients over 12 years old, the dosage is one g/day IV/IM for up to 14 days. After at least three days of parenteral therapy, patients may switch to an appropriate PO regimen if they improve clinically.

For complicated urinary tract infections, which including pyelonephritis, the dosage varies based on age. For patients below three months, the safety and efficacy of ertapenem are not established. For patients between three months to 12 years, the dosage is 15 mg/kg IV/IM every 12 hours for up to 14 days. The maximum dose should not exceed 1 g q12hr. After at least three days of parenteral therapy, patients may switch to an appropriate PO regimen if they improve clinically. For patients over 12 years old, the dosage is one g/day IV/IM for up to 14 days. After at least three days of parenteral therapy, patients may switch to an appropriate PO regimen if they improve clinically.

For acute pelvic infections, the dosage varies based on age. For patients below three months, the safety and efficacy of ertapenem are not established. For patients between three months to 12 years, the dosage is 15 mg/kg IV/IM every 12 hours for three to ten days. For patients over 12 years old, the dosage is one g/day IV/IM for three to ten days.

For complicated intra-abdominal infections, the dosage varies based on age. For patients below three months, the safety and efficacy of ertapenem are not established. For patients between three months to 12 years, the dosage is 15 mg/kg IV/IM every 12 hours for five to 14 days. For patients over 12 years old, the dosage is one g/day IV/IM for five to 14 days.

For complicated skin/skin structure infections, the dosage varies based on age. For patients below three months, the safety and efficacy of ertapenem are not established. For patients between three months to 12 years, the dosage is 15 mg/kg IV/IM every 12 hours for seven to 14 days. For diabetic foot infections, treatment may continue for up to four weeks, depending on the severity of the infection and response to therapy (excluding diabetic foot infections with osteomyelitis). For patients over 12 years old, the dosage is one g/day IV/IM for seven to 14 days. For diabetic foot infections, treatment may continue for up to four weeks, depending on the severity of the disease and response to therapy (excluding diabetic foot infections with osteomyelitis).

There are no specific dietary restrictions related to the use of Ertapenem. However, following a healthy and balanced diet is essential as part of overall health and wellness.

Ertapenem may be contraindicated under the following conditions:

• In patients with known hypersensitivity to Ertapenem, cephalosporin, penicillin, or any formulation component.

The physician should closely monitor the patients and keep pharmacovigilance as follows:

Ertapenem, a beta-lactam antibiotic, has been associated with serious and sometimes fatal hypersensitivity reactions, including anaphylaxis. Patients with a history of sensitivity to multiple allergens, including penicillins, cephalosporins, and other beta-lactams, may be at higher risk of experiencing such reactions. Patients should be thoroughly questioned about previous hypersensitivity reactions to these allergens before initiating therapy with Ertapenem. If an allergic reaction to Ertapenem occurs, the drug should be discontinued immediately, and emergency treatment with epinephrine, oxygen, intravenous steroids, and airway management, including intubation, should be initiated. Other therapy may also be necessary based on the individual case.

Treatment with Ertapenem may also result in seizures and other CNS adverse events, as well as pseudomembranous colitis, which has been reported with nearly all antibacterial agents. Pseudomembranous colitis can range in severity from mild to life-threatening and should be considered in patients presenting with diarrhea after receiving antibacterial agents. Treatment measures depend on the severity of the case and may include drug discontinuation, fluid and electrolyte management, protein supplementation, and antibacterial therapy effective against Clostridium difficile colitis, which is the primary cause of "antibiotic-associated colitis."

Lidocaine HCl is used as the diluent for intramuscular administration of Ertapenem, and the prescribing information for lidocaine HCl should be referred to for specific information on its use.

When taking antibiotics, it is generally recommended to avoid alcohol as it can increase the risk of certain side effects, such as stomach upset, nausea, dizziness, and headaches. Additionally, some antibiotics can interfere with the breakdown and elimination of alcohol, leading to higher blood alcohol levels and prolonging the effects of alcohol.

Ertapenem is excreted in human breast milk, so caution should be exercised when administering Ertapenem to nursing mothers.

Pregnancy Category B

Ertapenem has been found to cross the placental barrier in rats, but no evidence of developmental toxicity was observed in mice or rats at IV doses up to 700 mg/kg/day.

There are no adequate and well-controlled studies on pregnant women, so the use of Ertapenem during pregnancy is recommended only if clearly needed.

There are no known food warnings related to the use of Ertapenem.

The adverse reactions related to Ertapenem can be categorized as follows:

Common

• Diarrhea
• Nausea
• Headache
• Pain at the injection site

Less Common

• Vomiting
• Constipation
• Rash
• Itching
• Dizziness
• Abdominal pain
• Increased liver enzymes
• Decreased platelet count
• Increased blood creatinine

Rare

• Allergic reactions, including anaphylaxis
• Clostridioides difficile-associated diarrhea (CDAD)
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Seizures
• Hallucinations
• Confusion
• Peripheral neuropathy

The clinically relevant drug interactions of Ertapenem are briefly summarized here:

When ertapenem is taken together with probenecid, the latter can decrease the renal clearance of ertapenem by competing for active tubular secretion. This reduces the plasma and renal clearances by 20% and 35%, respectively, and increases the AUC by 25%. Although probenecid can increase the half-life of ertapenem from 4.0 to 4.8 hours, co-administration for this purpose is not recommended due to the small effect on half-life.

In vitro studies show that ertapenem does not inhibit the P-glycoprotein-mediated transport of digoxin or vinblastine, and it is not a substrate for P-glycoprotein-mediated transport. Additionally, in vitro studies in human liver microsomes indicate that ertapenem does not inhibit metabolism mediated by six cytochromes p450 (CYP) isoforms, including 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4. Therefore, drug interactions caused by inhibition of P-glycoprotein-mediated drug clearance or CYP-mediated drug clearance with these isoforms are unlikely.

No specific clinical drug interaction studies have been conducted other than with probenecid.

The following are the side effects involving Ertapenem:

• Nausea
• Headache
• Diarrhea
• Rash
• Pain or redness at the injection site
• Elevated liver enzymes
• Decreased platelet count
• Increased white blood cell count

Pregnancy:

Pregnancy Category B:

Ertapenem has been found to cross the placental barrier in rats, but no evidence of developmental toxicity was observed in mice or rats at IV doses up to 700 mg/kg/day.

There are no adequate and well-controlled studies on pregnant women, so the use of Ertapenem during pregnancy is recommended only if needed.

Nursing Mothers

Ertapenem is excreted in human breast milk, so caution should be exercised when administering Ertapenem to nursing mothers.

Pediatric Use

Ertapenem is considered safe and effective for pediatric patients between 3 months and 17 years of age, based on evidence from adequate and well-controlled studies in adults and pharmacokinetic data in pediatric patients.

Ertapenem is not recommended for use in infants under three months of age or in the treatment of meningitis in the pediatric population due to insufficient CSF penetration.

Geriatric Use

No overall differences in safety or effectiveness had been observed between elderly patients (65 years and older) and younger patients in Phase IIb/III studies.

Elderly patients are more likely to have decreased renal function, which may increase the risk of toxic reactions to Ertapenem, so dose selection should be carefully considered, and renal function monitoring may be useful.

Physicians should be knowledgeable as well as vigilant about the treatment and identification of overdosage of Ertapenem.

There is no specific guidance available regarding the treatment of an overdose with Ertapenem. However, it is unlikely that an intentional overdose would occur. In healthy adult volunteers, the intravenous administration of 2 g of Ertapenem over 30 minutes or 3 g over 1-2 hours resulted in an increased incidence of nausea. In clinical studies with adults, one patient experienced diarrhea and transient dizziness after receiving three 1 g doses of Ertapenem in a 24-hour period. In pediatric clinical studies, a single Intravenous dose of 40 mg/kg up to a maximum of 2 g did not cause any toxicity.

If an overdose occurs, Ertapenem should be discontinued, and supportive treatment should be provided until the drug is eliminated by the kidneys. Hemodialysis can remove Ertapenem from the body. In subjects with end-stage renal insufficiency, the plasma clearance of ertapenem increased by 30% when hemodialysis was performed immediately after administration. However, there is found to be no information available regarding the use of hemodialysis to treat an overdose of Ertapenem.

Pharmacodynamics

Ertapenem is an effective carbapenem antibiotic with a bactericidal action that depends on the time during which drug concentrations remain above the minimal inhibitory concentrations (MIC). This antibiotic is effective against a broad range of Gram-positive and Gram-negative aerobic and anaerobic bacteria. Ertapenem is resistant to hydrolysis by various beta-lactamases, including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases. However, it is not effective against metallo-beta-lactamases.

Pharmacokinetics

Pharmacokinetic Parameters:

• Absorption

After intramuscular administration of ertapenem at a dose of 1 g, reconstituted with 1% lidocaine HCl injection, USP (in saline without epinephrine), the drug is almost completely absorbed with a mean bioavailability of approximately 90%. The peak plasma concentrations (Cmax) are achieved in approximately 2.3 hours (Tmax).

• Distribution

Ertapenem is said to be highly bound to human plasma proteins, primarily albumin. In healthy young adults, the protein binding of ertapenem is found to be decrease as plasma concentrations increase. The apparent volume of distribution at steady state (Vss) of ertapenem in adults is found to be approximately 0.12 liter/kg, also approximately 0.2 liter/kg in pediatric patients aged 3 months to 12 years, and approximately 0.16 liter/kg in pediatric patients age

d 13 to 17 years.

• Metabolism

In healthy young adults, after infusion of 1 g Intravenous radiolabeled ertapenem, the plasma radioactivity consists predominantly (94%) of ertapenem. The major metabolite of ertapenem is found to be the inactive ring-opened derivative formed by hydrolysis of the beta-lactam ring. In the in-vitro studies indicated that ertapenem does not inhibit metabolism mediated by any of the following cytochrome p450 (CYP) isoforms: 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4.

• Elimination

Ertapenem is found to be eliminated primarily by the kidneys. The mean plasma half-life in the healthy young adults is approximately 4 hours, and also the plasma clearance is approximately is about 1.8 L/hour. The mean plasma half-life in pediatric patients aged 13 to 17 years is approximately four hours, and approximately 2.5 hours in pediatric patients aged 3 months to 12 years. Following the administration of 1 g Intravenous radiolabeled ertapenem to healthy young adults, approximately 80% is found to be recovered in urine and 10% in feces. Of the 80% recovered in urine, approximately 38% is excreted in the form of unchanged drug, and also approximately 37% as the ring-opened metabolite.

• https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021337Orig1s021.pdf
• https://reference.medscape.com/drug/Ertapenem-ertapenem-342561
• https://www.drugs.com/mtm/ertapenem.html
• https://www.webmd.com/drugs/2/drug-148185/ertapenem-intravenous/details
• https://go.drugbank.com/drugs/DB00303