Ertapenem

Pronunciation: (ER-ta-PEN-em)
Class: Carbapenem antibiotic

Trade Names

Invanz
- Injection, lyophilized powder for solution 1 g

Pharmacology

Inhibits bacterial cell wall synthesis.

Pharmacokinetics

Absorption

Bioavailability is approximately 90% (IM). T _max is approximately 2.3 h (IM).

Distribution

Approximately 85% to 95% protein bound (concentration dependent). Vd at steady state is approximately 0.12 L/kg in adults, 0.2 L/kg in children 3 mo to 12 y of age, and 0.16 L/kg in children 13 to 17 y of age.

Metabolism

Major metabolite is the inactive ring-opened derivative formed by hydrolysis of the beta-lactam ring.

Elimination

The half-life is approximately 4 h. Approximately 80% excreted in urine (approximately 38% as unchanged drug) and 10% in feces. Plasma Cl is approximately 1.8 L/h.

Special Populations

Renal Function Impairment

Unbound AUC increased 1.5- and 2.3-fold in those with mild and moderate renal function impairment, respectively. No dosage adjustment necessary. Unbound AUC increased 4.4- and 7.6-fold in those with advanced renal impairment and ESRD, respectively. Dosage adjustment required.

Hepatic Function Impairment

Pharmacokinetics have not been established.

Elderly

The total and unbound AUC increased 37% and 67%, respectively, in elderly patients relative to younger patients.

Children

Pharmacokinetic parameters in children 13 to 17 y of age are comparable with adults. Plasma Cl is approximately 2-fold higher in children 3 mo to 12 y of age compared with adults. The half-life is approximately 2.5 h in children 3 mo to 12 y of age.

Indications and Usage

Treatment of moderate to severe complicated intra-abdominal infections, complicated skin and skin structure infections (including diabetic foot infections without osteomyelitis), community-acquired pneumonia, complicated UTIs (eg, pyelonephritis), and acute pelvic infections (eg, postpartum endomyometritis, postsurgical gynecologic infections, septic abortion) caused by susceptible microorganisms; prophylaxis of surgical-site infection following elective colorectal surgery.

Contraindications

Hypersensitivity to any component of this product or to other drugs in the same class; patients who have demonstrated anaphylactic reactions to beta-lactams; patients with known sensitivity to local anesthetics of the amide type (IM use only).

Dosage and Administration

Acute Pelvic Infections
Adults and Children 13 y and older

IV/IM 1 g/day for 3 to 10 days.

Children 3 mo to 12 y of age

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

Community-Acquired Pneumonia or Complicated UTIs (eg, Pyelonephritis)
Adults and Children 13 y and older

IV/IM 1 g/day for 10 to 14 days.

Children 3 mo to 12 y of age

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

Complicated Intra-Abdominal Infections
Adults and Children 13 y and older

IV/IM 1 g/day for 5 to 14 days.

Children 3 mo to 12 y of age

IV/IM 15 mg/kg twice daily for 5 to 14 days. Max dose: 1 g/day.

Complicated Skin and Skin Structure Infections
Adults and Children 13 y and older

IV/IM 1 g/day for 7 to 14 days. Adults with diabetic foot infections received up to 28 d of treatment.

Children 3 mo to 12 y of age

IV/IM 15 mg/kg twice daily for 7 to 14 days. Max dose: 1 g/day.

Prophylaxis of Surgical Site Following Colorectal Surgery
Adults

IV 1 g 1 h prior to surgical incision.

Renal Function Impairment
Adults and Children 13 y and older

IV/IM CrCl 30 mL/min or less: 500 mg/day.

Children 3 mo to 12 y of age

IV/IM No data available.

Hemodialysis
Adults

IV/IM 500 mg within 6 h prior to hemodialysis and a supplemental dose of 150 mg following the hemodialysis session.

Children 3 mo to 12 y of age

IV/IM No data available.

General Advice

• Administer by IV infusion over 30 min, or alternatively by deep IM injection. Follow manufacturer's instructions for reconstitution.
• Do not coinfuse with other medications.

Storage/Stability

Store lyophilized powder below 77°F. Reconstituted solution for IV administration diluted in sodium chloride 0.9% injection may be stored at room temperature and used within 6 h or stored under refrigeration for 24 h and used within 4 h after removal from refrigeration. Protect from freezing. Use reconstituted solution for IM administration within 1 h of preparation.

Drug Interactions

Probenecid

Inhibits renal excretion of ertapenem; coadministration of probenecid to extend the ertapenem half-life is not recommended.

Valproic acid and derivatives

Valproic acid plasma concentrations may be decreased to subtherapeutic levels, leading to a loss of seizure control. Monitor valproic acid plasma concentrations and observe the patient for seizure activity. Consider adjusting the valproic acid dose as needed or using an alternative antibiotic. If ertapenem therapy is necessary, consider supplemental anticonvulsant therapy.

Adverse Reactions

Cardiovascular

Chest pain, hypertension, hypotension, tachycardia (2%).

CNS

Headache (7%); altered mental status (5%); insomnia (3%); dizziness (2%); anxiety, asthenia/fatigue, seizure (1%); dyskinesia, hallucinations, myoclonus, tremor (postmarketing).

Dermatologic

Diaper dermatitis (5%); rash (3%); cellulitis, erythema, pruritus (2%); dermatitis (1%).

EENT

Nasopharyngitis (2%); pharyngitis, viral pharyngitis (1%).

GI

Diarrhea (12%); vomiting (10%); nausea (9%); abdominal pain (5%); constipation (4%); acid regurgitation, Clostridium difficile infection or colitis, loose stools, nausea, small intestine obstruction (2%); abdominal abscess, dyspepsia, oral candidiasis, upper abdominal pain (1%).

Genitourinary

UTIs (4%); vaginitis (3%); dysuria (1%).

Lab Tests

Increased ALT (9%); increased AST (8%); increased platelet count, increased serum alkaline phosphatase (7%); decreased neutrophil count (6%); decreased Hgb (5%); decreased Hct, increased urine RBC, increased urine WBC (3%); decreased segmented neutrophils, decreased serum albumin, decreased serum potassium, decreased WBC, increased eosinophils, increased serum glucose, increased total serum bilirubin (2%); increased WBC, urine protein present (more than 1%); decreased platelet count, increased PT, increased serum creatinine, increased serum potassium (1%).

Local

Infused vein complication, pain (7%); erythema (4%); extravasation, phlebitis, phlebitis/thrombophlebitis, swelling (2%); induration, warmth (1%).

Respiratory

Cough (4%); atelectasis, dyspnea (3%); pneumonia, upper respiratory tract infection (2%); rales/rhonchi, respiratory distress, wheezing (1%).

Miscellaneous

Wound infections (7%); anemia (6%); fever (5%); edema/swelling, wound complication (3%); anastomotic leak, hypothermia, postoperative infection, wound secretion (2%); herpes simplex, leg pain, seroma, wound dehiscence (1%); anaphylaxis/anaphylactoid reactions, drug rash with eosinophilia and systemic symptoms (postmarketing).

Precautions

Monitor Periodic assessment of organ system function, including renal, hepatic, and hematopoietic, is advised during prolonged therapy. Monitor patient's response to therapy.

Pregnancy

Category B . Passage to the fetus should be expected. There is no evidence that any beta-lactam antibiotic causes developmental toxicity in humans at therapeutic doses.

Lactation

Excreted in breast milk. The effects on a breast-feeding infant are unknown, but are of doubtful clinical significance.

Children

Safety and efficacy not established in children younger than 3 mo.

Elderly

Because elderly patients are more likely to have decreased renal function, select dose with caution.

Hypersensitivity

Serious and occasionally fatal hypersensitivity reactions have been reported with beta-lactam therapy.

Renal Function

Adjust dose accordingly.

Superinfection

May result in bacterial or fungal overgrowth of nonsusceptible organisms.

CNS

Seizures and other CNS adverse reactions may occur.

C. difficile –associated diarrhea

Consider possibility in patients with diarrhea.

Overdosage

Symptoms

Diarrhea, dizziness, nausea.

Patient Information

• Advise patient to notify health care provider if infection does not improve or appears to worsen.
• Instruct patient to report the following symptoms to health care provider: black, furry tongue; diarrhea; difficulty breathing; hives; itching; loose, foul-smelling, watery, or bloody stools; rash; vaginal itching or discharge.
• Warn patient, family, or caregiver that if diarrhea containing blood or pus develops after discharge, this may be a sign of a serious disorder. Instruct patient to seek medical care if noted and not to treat at home.
• Advise patient to inform health care provider if they are taking valproic acid or divalproex sodium for seizures. Therapy modifications may be needed.

Copyright © 2009 Wolters Kluwer Health.