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Meropenem

Drug Nomenclature

Synonyms: ICI-194660; Meropeneemi; Meropenem; Meropenemum; SM-7338
BAN: Meropenem
USAN: Meropenem
INN: Meropenem [rINN (en)]
INN: Meropenem [rINN (es)]
INN: Méropénem [rINN (fr)]
INN: Meropenemum [rINN (la)]
INN: Меропенем [rINN (ru)]
Chemical name: (4R,5S,6S)-3-[(3S,5S)-5-Dimethylcarbamoylpyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid trihydrate
Molecular formula: C17H25N3O5S,3H2O =437.5
CAS: 96036-03-2 (meropenem); 119478-56-7 (meropenem trihydrate)
ATC code: J01DH02
Read code: y087S

The United States Pharmacopeia

Colourless to white crystals. Sparingly soluble in water; very slightly soluble in alcohol; practically insoluble in acetone and in ether; soluble in dimethylformamide and in 5% monobasic potassium phosphate solution. pH of a 1 % solution in water is between 4.0 and 6.0. Store in airtight containers.

Meropenem

Adverse Effects and Precautions

As for Imipenem. Meropenem is more stable to renal dehydropeptidase I than imipenem and use with cilastatin, which inhibits this enzyme, is not required. Meropenem may have less potential to induce seizures than imipenem (see also below).

Effects on the nervous system

Animal studies have indicated that meropenem induces fewer seizures than imipenem-cilastatin and clinical data from the manufacturer have substantiated this. Comparison of data from 4872 patients with a variety of infections (including meningitis) treated with meropenem with that from 4752 patients who received other antibacterials, principally cephalosporin-based regimens or imipenem-cilastatin, showed that meropenem was not associated with any greater risk of seizures than the other antibacterials and was likely to have less neurotoxic potential than imipenem-cilastatin, making it a suitable drug to use in the treatment of meningitis.

Interactions

Probenecid inhibits the renal excretion of meropenem thereby increasing its plasma concentrations and prolonging its elimination half-life.

Antiepileptics

For reports of decreased plasma-valproate concentrations (sometimes with loss of seizure control) attributed to meropenem.

Antimicrobial Action

As for Imipenem. Meropenem is slightly more active than imipenem against Enterobacteriaceae and slightly less active against Gram-positive organisms.

Pharmacokinetics

After intravenous injection of meropenem 0.5 and 1 g over 5 minutes, peak plasma concentrations of about 50 and 112 micrograms/mL respectively are attained. The same doses infused over 30 minutes produce peak plasma concentrations of 23 and 49 micrograms/mL, respectively. Meropenem has a plasma elimination half-life of about 1 hour; this may be prolonged in patients with renal impairment and is also slightly prolonged in children. Meropenem is widely distributed into body tissues and fluids including the CSF and bile. It is about 2% bound to plasma proteins. It is more stable to renal dehydropeptidase I than imipenem and is mainly excreted in the urine by tubular secretion and glomerular filtration. About 70% of a dose is recovered unchanged in the urine over a 12-hour period and urinary concentrations above 10 micrograms/mL are maintained for up to 5 hours after a 500-mg dose. Meropenem is reported to have one metabolite (ICI-213689), which is inactive and is excreted in the urine. Meropenem is removed by haemodialysis.

Uses and Administration

Meropenem is a carbapenem beta-lactam antibacterial with actions and uses similar to those of imipenem. It is more stable to renal dehydropeptidase I than imipenem and need not be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of susceptible infections including intra-abdominal infections, gynaecological infections, meningitis, respiratory-tract infections (including in cystic fibrosis patients), septicaemia, skin and skin structure infections, urinary-tract infections, and infections in immunocom-promised patients. For details of these infections and their treatment, see under Choice of Antibacterial. Meropenem is given intravenously as the trihydrate, but doses are expressed in terms of the amount of anhydrous meropenem; 1.14 g of meropenem trihydrate is equivalent to about 1 g of anhydrous meropenem. It is given by slow injection over 3 to 5 minutes or by infusion over 15 to 30 minutes in a usual adult dose of 0.5 to 1 g every 8 hours. A dose of 2 g every 8 hours is given for meningitis; doses of up to 2 g every 8 hours have also been used in cystic fibrosis. For details of reduced doses in renal impairment, see below. For details of doses in infants and children, see below.

Administration in children

Use of meropenem is licensed in both the UK and US for infants and children over 3 months of age and weighing less than 50 kg. The usual dose is 10 to 20 mg/kg every 8 hours. A dose of 40 mg/kg is given every 8 hours for meningitis; doses of 25 to 40 mg/kg every 8 hours have been used in children aged 4 to 18 years with cystic fibrosis. In addition, the BNFC suggests the following doses for those under 3 months of age:

  • neonates under 7 days of age: 20 mg/kg every 12 hours (or 40 mg/kg every 12 hours in severe infections and in meningitis)
  • neonates 7 to 28 days of age: 20 mg/kg every 8 hours (or 40 mg/kg every 8 hours in severe infections and in meningitis)
  • infants 1 to 3 months of age: 10 mg/kg every 8 hours (or 20 mg/kg every 8 hours in severe infections; 40 mg/kg every 8 hours in meningitis)

Administration in renal impairment

Doses of meropenem should be reduced in patients with renal impairment. The following doses may be given to adults based on creatinine clearance (CC):

  • CC 26 to 50 mL/minute: the usual dose given every 12 hours
  • CC 10 to 25 mL/minute: one-half the usual dose every 12 hours
  • CC less than 10 mL/minute: one-half the usual dose every 24 hours
  • haemodialysis patients: the usual dose after the dialysis session

Preparations

The United States Pharmacopeia 31, 2008: Meropenem for Injection.

Proprietary Preparations

Argentina: Meroefectil; Merotenk; Merozen; Merpem; Zeropenem; Australia: Merrem; Austria; Optinem; Belgium: Meronem; Brazil: Meronem; Meroxil; Canada: Merrem; Chile: Meronem; Czech Republic: Meronem; Denmark: Meronem; Finland: Meronem; Germany; Meronem; Greece: Meronem; Hong Kong; Meronem; Hungary: Meronem; India: Meronem; Indonesia: Merofen; Meronem; Ronem; Tripenem; Ireland: Meronem; Israel: Meronem; Italy: Merrem; Japan: Meropen; Malaysia: Meronem; Mexico: Merrem; The Netherlands: Meronem; Norway: Meronem; New Zealand: Merrem; Philippines: Meronem; Poland: Meronem; Portugal: Meronem; Russia: Meronem; South Africa; Meronem; Singapore; Meronem; Spain: Meronem; Sweden: Meronem; Switzerland: Meronem; Thailand: Meronem; Turkey: Meronem; United Kingdom (UK): Meronem; United States of America (US or USA): Merrem; Venezuela: Meronem.

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