Meropenem

Generic name
Meropenem
Brand name
ATC Code
J01DH02
Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Pharmacokinetics in children

The following median pharmacokinetic parameters at steady state have been estimated from a population pharmacokinetic model (based on 753 samples from 188 preterm and term neonates (Smith et al. 2011):

Postmenstrual age <32 weeks <32 weeks ≥32 weeks ≥32 weeks
Postnatal age <14 days ≥14 days <14 days ≥14 days
n= 39 103 31 27
Dose (mg/kg/day) 40 in 2 doses 60 in 3 doses 90 in 3 doses 90 in 3 doses
Cmax (µg/ml) 44,3 46,5 44,9 61
t½ (hour) 3,82 2,68 2,33 1,58
Cl (l/hour/kg) 0,089 0,122 0,135 0,202
Vd (l/kg) 0,489 0,467 0,463 0,451

Other PK parameters (SmPC):

Age Cl t½
2 – 5 months 4,3 ml/min/kg 1,6 hour
6 – 23 months 5,3 ml/min/kg 1 hour
2 – 5 years 6,2 ml/min/kg 1 hour
6 – 12 years 5,8 ml/min/kg 1 hour

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Go to:

Severe bacterial infections
  • Intravenous
    • Preterm neonates Gestational age < 32 weeks
      [1] [6] [7] [8] [9] [10] [11]
        • Postnatal age < 2 weeks:
          • 40 mg/kg/dag in 2 doses
            Dose may be doubled in MIC >4 
        • Postnatal age > 2 weeks:
          • 60 mg/kg/dag in 3 doses
            Dose may be doubled in MIC >4 .
    • Preterm and full-term neonates Gestational age ≥ 32 weeks
      [1] [6] [7] [8] [9] [10] [11]
        • Postnatal age < 2 weeks:
          • 60 mg/kg/dag in 3 doses
            Dose may be doubled in MIC >4 .
        • Postnatal age > 2 weeks to 3 months:
          • 90 mg/kg/dag in 3 doses
            Dose may be increased to 120 mg/kg/day in 3 doses in MIC > 4
    • 3 months up to 18 years
      [2] [4] [5]
      • 60 mg/kg/day in 3 doses. Max: 6 g/day.

      • A lower dose is recommended for children older than 3 months compared to children younger than 3 months; this lower dose is the licensed dose (on-label), while meropenem is not licensed for children under 3 months of age (off-label). Available scientific literature has shown that children under 3 months require a higher dose. It is as yet unclear whether a higher dose is also necessary in older children in the treatment of bacterial infections other than meningitis or infections in CF.
Meningitis
  • Intravenous
    • Preterm neonates Gestational age < 32 weeks
      [9] [10]
        • Postnatal age < 2 weeks:
          • 80 mg/kg/dag in 2 doses
        • Postnatal age > 2 weeks:
          • 120 mg/kg/dag in 3 doses
    • Premature and full-term neonates Gestational age ≥ 32 weeks
      [9] [10]
      • Independent of postnatal age:  120 mg/kg/day in 3 doses.
    • 1 month up to 18 years
      [2] [4] [5]
      • 120 mg/kg/day in 3 doses. Max: 6 g/day.
Infections in cystic fibrosis
  • Intravenous
    • 1 month up to 18 years
      [1] [4]
      • 120 mg/kg/day in 3 doses. Max: 6 g/day.

      • Alternative: 100 mg/kg/day continuous infusion
General dosing information
  • Intravenous
    • 0 years up to 18 years
      [10]

      • Shabaan et al. (2017) showed that an infusion duration of 4 hours gave better results than an infusion duration of 30 minutes. Clinical improvement and microbial eradication occurred earlier. In addition, mortality, duration of respiratory support and occurrence of acute renal failure were lower.

Renal impaiment in children > 3 months

Adjustment in renal impairment as specified:

GFR 50-80 ml/min/1.73 m2
Adjustment not necessary
GFR 30-50 ml/min/1.73 m2
100 percentage of single dose and dosing interval : 12 uur
GFR 10-30 ml/min/1.73 m2
First dose: 100% of normal single dose. Consecutive doses: 50%. Dosing interval 12 hours
GFR < 10 ml/min/1.73 m2
First dose: 100% of normal single dose. Consecutive doses: 50%. Dosing interval: 24 hours
Clinical consequences

Side effects are inter alia gastrointestinal problem, headaches, paraesthesia, oral and vaginal candidiasis, reversible thrombocytosis, eosinophilia, thrombocytopenia and neutropenia, reversible increase of hepatic function values.

Patients on dialysis

Haemodialysis and peritoneal dialysis: 50% of the normal dose each time and the interval between two doses: 24 hours

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

The safetyprofile in children seems to be similar to the adult profile. [SmPC]

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Meropenem is a reserve antibiotic. In cases of cystic fibrosis: strictly when indicated, always combined with an aminoglycoside.

Concomittant use with valproic acide should be avoided. valproic acid levels are decreased and do no recover by increasing the dose of valproic acid. Select an alternativ antibiotic agent.

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

OTHER BETA-LACTAM ANTIBACTERIALS

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

First-generation cephalosporins
J01DB04
J01DB01
Second-generation cephalosporins
J01DC02
Third-generation cephalosporins
J01DD08
J01DD01
J01DD52
J01DD02
J01DD04

References

  1. Hartwig NC, et al, Vademecum pediatrische antimicrobiële therapie, 2005
  2. AstraZeneca BV, SPC Meronem (RVG 17864), www.cbg-meb.nl, Geraadpleegd 10 juni 2010, http://db.cbg-meb.nl/IB-teksten/h17864.pdf
  3. Hexal, SmPC Meropenem HEXAL® Pulver zur Herstellung einer Injektions- bzw. Infusionslösung (92099.00.00/92100.00.00), 05/2017
  4. Centrafarm BV, SmPC Meropenem (RVG 109673) 15-06-2018, www. geneesmiddeleninformatiebank.nl
  5. Dr. Friedrich Eberth, SmPC Meropenem Dr. F. Eberth 500 mg Plv. z. Herst. e. Inj.-/Inf.lsg. (1-31186), https://www.univadis.at/, 05/2018
  6. Pfizer, Inc. , Prescribing information Merrem IV (FDA label) rev. 04/2019, https://www.accessdata.fda.gov.
  7. Bradley, J. S., et al , Meropenem pharmacokinetics, pharmacodynamics, and Monte Carlo simulation in the neonate, Pediatr Infect Dis J, 2008, 27(9), 794-9
  8. Lutsar, I. et al, Meropenem vs standard of care for treatment of neonatal late onset sepsis (NeoMero1): A randomised controlled trial. , PLoS One, 2020, 15(3), e0229380
  9. Germovsek, E., et al , Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies, J Antimicrob Chemother, 2018, 73(7), 1908-1916
  10. Shabaan, A. E., , Conventional Versus Prolonged Infusion of Meropenem in Neonates With Gram-negative Late-onset Sepsis: A Randomized Controlled Trial., Pediatr Infect Dis J, 2017, 36(4), 358-363
  11. Smith, P.B. et al, Population pharmacokinetics of meropenem in plasma and cerebrospinal fluid of infants with suspected or complicated intra-abdominal infections. , Pediatr Infect Dis J , 2011, 30(10), 844-9
  12. Costenaro P, et al., Optimizing Antibiotic Treatment Strategies for Neonates and Children: Does Implementing Extended or Prolonged Infusion Provide any Advantage?, Antibiotics (Basel)., 2020, Jun 17;9(6), 329; PMID: 32560411

Changes

Therapeutic Drug Monitoring


Overdose