No

Antibiotic, Carbapenem

Intra-abdominal infections (complicated appendicitis and peritonitis) caused by viridans group streptococci, E. coli, K. pneumoniae, P. aeruginosa, B. fragilis, B. thetaiotaomicron, and Peptostreptococcus sp; also indicated for bacterial meningitis in pediatric patients >3 months of age caused by S. pneumoniae, H. influenzae, and N. meningitidis; meropenem has also been used to treat soft tissue infections, febrile neutropenia, and urinary tract infections

B

Although no teratogenic or infant harm has been found in studies, excretion in breast milk is not known and this drug should be used during pregnancy and lactation only if clearly indicated

Patients with known hypersensitivity to meropenem, any component, or other carbapenems (eg, imipenem); patients who have experienced anaphylactic reactions to other beta-lactams

Pseudomembranous colitis and hypersensitivity reactions have occurred and often require immediate drug discontinuation; thrombocytopenia has been reported in patients with significant renal dysfunction; seizures have occurred in patients with underlying neurologic disorders (less frequent than with Primaxin®); safety and efficacy have not been established for children <3 months of age; superinfection possible with long courses of therapy

1% to 10%:

Central nervous system: Headache (2.8%)

Dermatologic: Rash, pruritus (1% to 2%)

Gastrointestinal: Diarrhea (5%), nausea/vomiting (4%), constipation (1.2%)

Local: Pain at injection site (3%), phlebitis, thrombophlebitis (1%)

Respiratory: Apnea (1.2%)

<1%: Hypotension, heart failure (MI and arrhythmias), tachycardia, hypertension, edema, seizures, insomnia, agitation, confusion, hallucinations, depression, seizures, fever, urticaria, anorexia, flatulence, ileus, oral moniliasis, glossitis, dysuria, RBCs in urine, cholestatic jaundice, hepatic failure, increase LFTs, anemia, hypo- and hypercytosis, bleeding events (epistaxis, melena, etc), paresthesia, whole body pain, renal failure, increased creatinine/BUN

No cases of acute overdosage are reported which have resulted in symptoms

Supportive therapy recommended; meropenem and metabolite are removable by dialysis

Increased effect: Probenecid competes with meropenem for active tubular secretion and inhibits the renal excretion of meropenem (half-life increased by 38%)

Store at room temperature; when vials are reconstituted with NaCl/D₅W, they are stable for 2 hours/1 hour at room temperature or for 18 hours/8 hours when refrigerated; when diluted in minibags, they are stable for up to 24 hours refrigerated in NaCl and 6 hours in D₅W

Inhibits bacterial cell wall synthesis by binding to several of the penicillin-binding proteins, which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis; bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested

Distribution: V_d: ~0.3 L/kg in adults (0.4-0.5 L/kg in children); penetrates well into most body fluids and tissues; CSF concentrations approximate those of the plasma

Protein binding: 2%

Metabolism: Hepatic; metabolizes to open beta-lactam form (inactive); not metabolized by same enzyme as imipenem which results in toxic metabolite

Half-life:

Normal renal function: 1-1.5 hours

Cl_cr 30-80 mL/minute: 1.9-3.3 hours

Cl_cr 2-30 mL/minute: 3.82-5.7 hours

Time to peak tissue concentration: 1 hour following infusion

Elimination: Renal, ~25% as the inactive metabolite

I.V.:

Preterm: 20 mg/kg/dose every 12 hours (may be increased to 40 mg/kg/dose if treating a highly resistant organism such as Pseudomonas aeruginosa)

Full-term (<3 months of age): 20 mg/kg/dose every 8 hours (may be increased to 40 mg/kg/dose if treating a highly resistant organism such as Pseudomonas aeruginosa)

Children >3 months (<50 kg):

Intra-abdominal infections: 20 mg/kg every 8 hours (maximum dose: 1 g every 8 hours)

Meningitis: 40 mg/kg every 8 hours (maximum dose: 2 g every 8 hours)

Children >50 kg:

Intra-abdominal infections: 1 g every 8 hours

Meningitis: 2 g every 8 hours

Adults: 1 g every 8 hours

Dosing adjustment in renal impairment: Adults:

Cl_cr 26-50 mL/minute: Administer 1 g every 12 hours

Cl_cr 10-25 mL/minute: Administer 500 mg every 12 hours

Cl_cr <10 mL/minute: Administer 500 mg every 24 hours

Dialysis: Meropenem and its metabolites are readily dialyzable

Continuous arteriovenous or venovenous hemodiafiltration (CAVH) effects: Dose as Cl_cr 10-50 mL/minute

Monitor for signs of anaphylaxis during first dose

May rarely cause agitation, confusion, insomnia, hallucinations, or depression

None reported

No information available to require special precautions

1% to 10% of patients will experience oral moniliasis and glossitis

Report pain at infusion/injection site, rash, or respiratory difficulty. You may experience gastric distress, diarrhea, mouth sores, respiratory difficulty, or headache (consult prescriber for appropriate medication). Breast-feeding precautions: Consult prescriber if breast-feeding.

Infusion: 500 mg (100 mL); 1 g (100 mL)

Infusion, ADD-vantage®: 500 mg (15 mL); 1 g (15 mL)

Injection: 25 mg/mL (20 mL); 33.3 mg/mL (30 mL)

Blummer JL, Reed MD, Kearns GL, et al, "Sequential, Single-Dose Pharmacokinetic Evaluation of Meropenem in Hospitalized Infants and Children," Antimicrob Agents Chemother, 1995, 39(8):1721-5.

Bradley, JS, "Meropenem: A New, Extremely Broad Spectrum Beta-lactam Antibiotic for Serious Infections in Pediatrics," Pediatr Infect Dis J, 1997, 16:263-8.

Craig WA, "The Pharmacology of Meropenem, a New Carbapenem Antibiotic," Clin Inf Dis, 1997, 24(Suppl 2):S266-75.

Fish DN and Singletary TJ, "Meropenem, A New Carbapenem Antibiotic," Pharmacotherapy, 1997, 17(4):644-69.

Hellinger WC and Brewer NS, "Carbapenems and Monobactams: Imipenem, Meropenem, and Aztreonam," Mayo Clin Proc, 1999, 74(4):420-34.

Krueger WA, Schroeder TH, Hutchison M, et al, "Pharmacokinetics of Meropenem in Critically Ill Patients With Acute Renal Failure Treated by Continuous Hemodiafiltration," Antimicrob Agents Chemother, 1998, 42(9):2421-4.

Ljungberg B and Nilsson-Ehle I, "Pharmacokinetics of Meropenem an Its Metabolites in Young and Elderly Healthy Men," Antimicrob Agents Chemother, 1992, 36(7):1437-40.

Wiseman LR, Wagstaff AJ, Brogden RN, et al, "Meropenem. A Review of its Antibacterial Activity, Pharmacokinetic Properties and Clinical Efficacy," Drugs, 1995, 50(1):73-101.