Each vial contains Meropenem (as trihydrate) 1.38 g equivalent to Meropenem 1 gram.
Properties: Meropenem (MEROPEVEX) is 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.
Pharmacology: Pharmacodynamics: 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.
Pharmacokinetics: Following 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 approximately 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.
Microbiology: Antimicrobial Actions: Meropenem is slightly more active than imipenem against Enterobacteriaceae and slightly less active against Gram-positive organisms. Like Imipenem, it is bactericidal and acts similarly to the penicillins by inhibiting synthesis of the bacterial cell wall. It has a very broad spectrum of activity in vitro, including activity against Gram-positive and Gram-negative aerobic and anaerobic organisms, and is stable to hydrolysis by beta-lactamases produced by most bacterial species. Cilastatin, the enzyme inhibitor given in association with imipenem, appears to have no antibacterial activity.
Most Gram-positive cocci are sensitive including most streptococci, and both penicillinase- and non-penicillinase-producing staphylococci, although its activity against methicillin-resistant Staphylococcus aureus is variable. Imipenem has good to moderate activity against Enterococcus faecalis, but most E. faecium are resistant. Nocardia, Rhodococcus, and Listeria spp. are also sensitive.
Among Gram-negative bacteria, imipenem is active against many of the Enterobacteriaceae including Citrobacter and Enterobacter spp., Escherichia coli, Klebsiella, Proteus, Providencia, Salmonella, Serratia, Shigella, and Yersinia spp. Its activity against Pseudomonas aeruginosa is similar to that of ceftazidime. Imipenem is also active against Acinetobacter spp. and Campylobacter jejuni, and also against Haemophilus influenzae and Neisseria spp., including beta-lactamase-producing strains.
It is used in the treatment of susceptible infections including intra-abdominal infections, meningitis, respiratory-tract infections (including in cystic fibrosis patients), septicaemia, skin and skin structure infections, urinary-tract infections, and infections in immuno-compromised patients.
Meropenem (MEROPEVEX) 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, increased to 2 g every 8 hours for meningitis; doses of up to 2 g every 8 hours have also been used in cystic fibrosis.
Children over 3 months of age and weighing less than 50 kg may be given 10 to 20 mg/kg every 8 hours, increased to 40 mg/kg every 8 hours for meningitis. Doses of 25 to 40 mg/kg every 8 hours have been used in children with cystic fibrosis.
Dosage adjustment for patients with Renal Impairment: Meropenem (MEROPEVEX) should be reduced in patients with renal impairment. The following doses may be given 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.
Direction for Reconstitution: For intravenous bolus injection, MEROPEVEX should be dissolved in sterile water for injection (5 mL per 250 mg of Meropenem). This produces a concentration of approximately 50 mg/mL. Solutions that are ready to use are clear, and colorless or pale yellow.
Meropenem is contraindicated in patients with known allergy to Carbapenem group of antibiotics.
Meropenem is more stable to renal dehydropeptidase I than imipenem and administration with cilastatin, which inhibits this enzyme, is not required. Meropenem may have less potential to induce seizures than imipenem. Hypersensitivity reactions such as skin rashes, urticaria, eosinophilia, fever, and, rarely, anaphylaxis may occur. Gastrointestinal effects include nausea, vomiting, diarrhoea, tooth or tongue discoloration, and altered taste. Superinfection with non-susceptible organisms such as Enterococcus faecium
, strains of Pseudomonas aeruginosa
with acquired resistance, and Candida
may also occur. Pseudomembranous colitis may develop. Erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely. Increases in liver enzymes and abnormalities in haematological parameters, including a positive Coombs' test, have been noted in Imipenem.
Probenecid inhibits the renal excretion of meropenem thereby increasing its plasma concentrations and prolonging its elimination half-life.
Antiepileptics: Decreases in plasma concentrations of valproic acid to subtherapeutic levels have been noted in 2 patients during therapy with meropenem and amikacin. Meropenem was regarded as the likely cause of the interaction with valproic acid. Marked reductions in valproate concentrations have also been reported in 3 children given panipenem (with betamipron).
Store at temperatures not exceeding 30°C. Protect from light.
J01DH02 - meropenem ; Belongs to the class of carbapenems. Used in the systemic treatment of infections.
Powd for inj (vial) 1 g x 10's.