Pediatric Formulary

Dosages

Side effects in children

Warnings & precautions in children

Contra-indications in children

Interactions

Renal impairment

References

Meropenem

Generic name

Meropenem

Brand name

ATC Code

J01DH02

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

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

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Available formulations

No information is present at this moment.

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Dosages

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.

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.

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.

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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

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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]

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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.

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Interactions

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

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First-generation cephalosporins
	Cefazolin Related Medicines Menu">	J01DB04
	Cephalexin Related Medicines Menu">	J01DB01

Second-generation cephalosporins
	Cefuroxime (as the sodium salt), cefuroxime (as cefuroxime axetil) Related Medicines Menu">	J01DC02

Third-generation cephalosporins
	Cefixim Related Medicines Menu">	J01DD08
	Cefotaxime (as the sodium salt) Related Medicines Menu">	J01DD01
	Ceftazidim + Avibactam Related Medicines Menu">	J01DD52
	Ceftazidime Related Medicines Menu">	J01DD02
	Ceftriaxone Related Medicines Menu">	J01DD04

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References

Hartwig NC, et al, Vademecum pediatrische antimicrobiële therapie, 2005
AstraZeneca BV, SPC Meronem (RVG 17864), www.cbg-meb.nl, Geraadpleegd 10 juni 2010, http://db.cbg-meb.nl/IB-teksten/h17864.pdf
Hexal, SmPC Meropenem HEXAL® Pulver zur Herstellung einer Injektions- bzw. Infusionslösung (92099.00.00/92100.00.00), 05/2017
Centrafarm BV, SmPC Meropenem (RVG 109673) 15-06-2018, www. geneesmiddeleninformatiebank.nl
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
Pfizer, Inc. , Prescribing information Merrem IV (FDA label) rev. 04/2019, https://www.accessdata.fda.gov.
Bradley, J. S., et al , Meropenem pharmacokinetics, pharmacodynamics, and Monte Carlo simulation in the neonate, Pediatr Infect Dis J, 2008, 27(9), 794-9
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
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
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
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
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

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Meropenem

Meropenem

Pharmacokinetics in children

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

Available formulations

Dosages

Renal impaiment in children > 3 months

GFR 50-80 ml/min/1.73 m2

GFR 30-50 ml/min/1.73 m2

GFR 10-30 ml/min/1.73 m2

GFR < 10 ml/min/1.73 m2

Clinical consequences

Patients on dialysis

Side effects in children

Contra-indications

Warnings & precautions in children

Interactions

References

Changes

Changes