Dosing

Dosing: Adult

Meningitis	I.V.: 2 g every 8 hours
intra-abdominal infections, complicated	I.V.: 1 g every 8 hours
Pneumonia (nosocomial)	I.V.: 1 g every 8 hours
Septicemia	I.V.: 1 g every 8 hours
Febrile neutropenia	I.V.: 1 g every 8 hours
diabetic foot	I.V.: 1 g every 8 hours
Pneumonia (community-acquired)	I.V.: 500 mg every 8 hours
Skin and skin structure infections	I.V.: 500 mg every 8 hours
Urinary tract infections (complicated)	I.V.: 500 mg every 8 hours

Dosing: Pediatric
Usual dosage range: Children ≥3 months: I.V.: 30-120 mg/kg/day divided every 8 hours (maximum dose: 6 g/day)

Meningitis	40 mg/kg every 8 hours (maximum dose: 2 g every 8 hours)
intra-abdominal infections, complicated	20 mg/kg every 8 hours (maximum dose: 1 g every 8 hours)
Febrile neutropenia	20 mg/kg every 8 hours (maximum dose: 1 g every 8 hours)
Pneumonia (community-acquired)	10-20 mg/kg every 8 hours (maximum dose: 1 g every 8 hours)
Skin and skin structure infections	10-20 mg/kg every 8 hours (maximum dose: 1 g every 8 hours)
Urinary tract infections (complicated)	10 mg/kg every 8 hours (maximum dose: 500 mg every 8 hours)

Dosing: Renal Impairment
Clcr 26-50 mL/minute: Administer recommended dose based on indication every 12 hours
Clcr 10-25 mL/minute: Administer one-half recommended dose based on indication every 12 hours
Clcr <10 mL/minute: Administer one-half recommended dose based on indication every 24 hours

Administration
1- Administer I.V. infusion over 15-30 minutes;
2- I.V. bolus injection (5-20 mL) over 3-5 minutes
3- Extended infusion administration (unlabeled dosing): Administer over 3 hours (Crandon 2011; Dandekar, 2003).

Use

Treatment of intra-abdominal infections (complicated appendicitis and peritonitis); treatment of bacterial meningitis in pediatric patients ≥3 months of age caused by S. pneumoniae, H. influenzae, and N. meningitidis; treatment of complicated skin and skin structure infections caused by susceptible organisms
Canadian labeling: Additional indications (not in U.S. labeling): Treatment of lower respiratory tract infections (community-acquired and nosocomial pneumonias), complicated urinary tract infections, gynecologic infections (excluding chlamydia), and septicemia; treatment of bacterial meningitis in adults caused by S. pneumoniae, H. influenzae, and N. meningitidis (use in adult meningitis based on pediatric data)

Adverse Reactions

•    Safety profile of meropenem: a review of nearly 5,000 patients treated with meropenem.
meropenem-related adverse reactions most frequently reported were
•    Rash (1.4%).
•    Diarrhea  (2.3%). 
•    Nausea/vomiting (1.4%).
•    Seizure (0.08%).
•    The most commonly reported meropenem-related laboratory adverse events were
•    thrombocytosis (1.6 %)
•    increased hepatic enzymes (1.5-4.3 %).

Contraindications

Hypersensitivity to meropenem, any component of the formulation, or other carbapenems (eg, doripenem, ertapenem, imipenem); patients who have experienced anaphylactic reactions to other beta-lactams

Warnings / Precautions Drug

Concerns related to adverse effects:
• Anaphylaxis/hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylaxis, have been reported (some without a history of previous allergic reactions to beta-lactams).
• CNS effects: Carbapenems have been associated with CNS adverse effects, including confusional states and seizures (myoclonic); use caution with CNS disorders (eg, brain lesions and history of seizures) and adjust dose in renal impairment to avoid drug accumulation, which may increase seizure risk.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required in patients with moderate-to-severe renal dysfunction. Increased seizure risk and thrombocytopenia have been reported in patients with renal dysfunction.
Concurrent drug therapy issues:
• Valproic acid and derivatives: Carbapenems, including meropenem, may decrease the serum concentration of divalproex sodium/valproic acid increasing the risk of breakthrough seizures. Concurrent use of carbapenem antibiotics with divalproex sodium/valproic acid is generally not recommended. Alternative antimicrobial agents should be considered, but if a concurrent carbapenem is necessary, consider additional antiseizure medication.
Special populations:
• Elderly: Lower doses (based upon renal function) are often required in the elderly.

Interactions

BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Divalproex: Carbapenems may decrease the serum concentration of Divalproex. Management: Concurrent use of carbapenem antibiotics with divalproex is generally not recommended. Alternative antimicrobial agents should be considered, but if a concurrent carbapenem is necessary, consider additional anti-seizure medication. Risk D: Consider therapy modification
Probenecid: May increase the serum concentration of Meropenem. Risk X: Avoid combination
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Valproic Acid: Carbapenems may decrease the serum concentration of Valproic Acid. Management: Concurrent use of carbapenem antibiotics with valproic acid is generally not recommended. Alternative antimicrobial agents should be considered, but if a concurrent carbapenem is necessary, consider additional anti-seizure medication. Risk D: Consider therapy modification

Pregnancy

B

Lactation

 Excretion in breast milk unknown/use caution

Mechanism of Action

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

Pharmacodynamics / Kinetics

Distribution: penetrates well into most body fluids and tissues; CSF concentrations approximate those of the plasma
Protein binding: ~2%
Metabolism: Hepatic; metabolized to open beta-lactam form (inactive)
Half-life elimination:  Normal renal function: 1-1.5 hours
Time to peak, tissue: 1 hour following infusion
Excretion: Urine (~70% as unchanged drug)