Meropenem

Introduction: Meropenem is an ultra-broad spectrum injectable antibiotic used to

treat a wide variety of infections, including meningitis and pneumonia.
Mechanism of action: Meropenem is bactericidal except against Listeria
monocytogenes where it is bacteriostatic. It inhibits bacterial wall synthesis like
other beta-lactam antibiotics. In contrast to other beta-lactams, it is highly
resistant to degradation by beta-lactamases or cephalosporinases. Resistance
generally arises due to mutations in penicillin binding proteins, production of
metallo-beta-lactamases, or resistance to diffusion across the bacterial outer
membrane. Unlike imipenem, it is stable to dehydropeptidase-1 and can
therefore be given without cilastatin.
Pharmacology:
Distribution: Vd: Adults: ~0.3 L/kg, Children: 0.4-0.5 L/kg; 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
Clcr 30-80 mL/minute: 1.9-3.3 hours
Clcr 2-30 mL/minute: 3.82-5.7 hours
Time to peak, tissue: 1 hour following infusion
Excretion: Urine (~25% as inactive metabolites)
Indications: To reduce the development of drug-resistant bacteria and maintain
the effectiveness of Meropenem and other antibacterial drugs, Meropenem
should only be used to treat or prevent infections that are proven or strongly
suspected to be caused by susceptible bacteria. Meropenem is indicated as
single agent therapy for the treatment of the following infections when caused by
susceptible isolates of the designated microorganisms:
Skin and Skin Structure Infections: Complicated skin and skin structure
infections due to Staphylococcus aureus (-lactamase and non--lactamase
producing, methicillin susceptible isolates only), Streptococcus pyogenes,
Streptococcus agalactiae, viridans group streptococci , Enterococcus faecalis
(excluding
vancomycin-resistant
isolates),
Pseudomonas
aeruginosa,
Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus
species.
Intra-abdominal Infections: Complicated appendicitis and peritonitis caused by
viridans group streptococci, Escherichia coli, Klebsiella pneumoniae,
Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and
Peptostreptococcus species.

Bacterial Meningitis (Pediatric patients > 3 months only): Bacterial

meningitis caused by Streptococcus pneumoniae , Haemophilus influenzae (lactamase and non--lactamase-producing isolates), and Neisseria meningitidis.
Dosage:
Adults: The recommended dose of Meropenem 500 mg given every 8 hours for
skin and skin structure infections and 1 g given every 8 hours for intra-abdominal
infections Meropenem should be administered by intravenous infusion over
approximately 15 to 30 minutes. Doses of 1 g may also be administered as an
intravenous bolus injection (5 to 20 mL) over approximately 3-5 minutes.
Use in Adults with Renal Impairment: Dosage should be reduced in patients
with creatinine clearance less than 51 mL/min. (see dosing table below).
Recommended Meropenem Dosage Schedule for
Renal Function
Creatinine
Dose
Clearance
(dependent on type of
(mL/min)
infection)
Recommended dose (500 mg
51
cSSSI
and
1g
Intraabdominal)

Adults with Impaired

Dosing
Interval
Every 8 hours

Every
12
hours
Every
12
10-25
One-half recommended dose
hours
Every
24
< 10
One-half recommended dose
hours
When only serum creatinine is available, the following formula (Cockcroft and
Gault equation)5 may be used to estimate creatinine clearance.
Males:
Creatinine
Clearance
Weight (kg) x (140 - age)
(mL/min)=
72 x serum creatinine
(mg/dL)
Females: 0.85 x above value
There is inadequate information regarding the use of Meropenem in patients on
hemodialysis.
Use in Elderly Patients: No dosage adjustment is required for elderly patients
with creatinine clearance values above 50 mL/min.
Use in Pediatric Patients: For pediatric patients from 3 months of age and
older, the Meropenem dose is 10, 20 or 40 mg/kg every 8 hours (maximum dose
is 2 g every 8 hours), depending on the type of infection (complicated skin and
skin structure, intra-abdominal or meningitis). (See dosing table below.) Pediatric
patients weighing over 50 kg should be administered Meropenem at a dose of
500 mg every 8 hours for complicated skin and skin structure infections, 1 g
every 8 hours for intra-abdominal infections and 2 g every 8 hours for meningitis.
Meropenem should be given as intravenous infusion over approximately 15 to 30
26-50

Recommended dose

minutes or as an intravenous bolus injection (5 to 20 mL) over approximately 3-5

minutes.
Recommended Meropenem Dosage Schedule for Pediatrics With Normal
Renal Function
Up
to
a
Type
of
Dosing
Dose (mg/kg) Maximum
Infection
Interval
Dose
Complicated 10
500 mg
Every 8 hours
skin and skin
structure
20
1g
Every 8 hours
Intraabdominal
Meningitis
40
2g
Every 8 hours
There is no experience in pediatric patients with renal impairment.
Side effects: Nausea, diarrhea, headache or pain/redness at the injection site
may occur. If these effects persist or worsen, notify your doctor promptly. Tell
your doctor immediately if you have any of these highly unlikely but very serious
side effects: stomach pain, black/bloody stools, white patches in the mouth,
fever, mental/mood changes, unusually fast/slow/irregular pulse, chest pain,
seizures, change in amount of urine, yellowing eyes or skin. An allergic reaction
to this drug is unlikely, but seeks immediate medical attention if it occurs.
Symptoms of an allergic reaction include: rash, itching, swelling, dizziness,
trouble breathing. If you notice other effects not listed above, contact your doctor
or pharmacist.
Precautions:
General: Prescribing Meropenem in the absence of a proven or strongly
suspected bacterial infection or a prophylactic indication is unlikely to provide
benefit to the patient and increases the risk of the development of drug-resistant
bacteria. Seizures and other adverse CNS experiences have been reported
during treatment with Meropenem These experiences have occurred most
commonly in patients with CNS disorders (e.g., brain lesions or history of
seizures) or with bacterial meningitis and/or compromised renal function.
Pregnancy Category B: There are, however, no adequate and well-controlled
studies in pregnant women. Because animal reproduction studies are not always
predictive of human response, this drug should be used during pregnancy only if
clearly needed.
Pediatric Use: The safety and effectiveness of Meropenem have been
established for pediatric patients 3 months of age. Use of Meropenem in
pediatric patients with bacterial meningitis is supported by evidence from
adequate and well-controlled studies in the pediatric population.
Nursing Mothers: It is not known whether this drug is excreted in human milk.
Because many drugs are excreted in human milk, caution should be exercised
when Meropenem is administered to a nursing woman.

Geriatric Use: Meropenem is known to be substantially excreted by the kidney,

and the risk of toxic reactions to this drug may be greater in patients with
impaired renal function. Because elderly patients are more likely to have
decreased renal function, care should be taken in dose selection, and it may be
useful to monitor renal function.
Contraindications: Meropenem is contraindicated in patients with known
hypersensitivity to any component of this product or to other drugs in the same
class or in patients who have demonstrated anaphylactic reactions to -lactams.
How supplied: Customized as per request.