• Pneumonias and Nosocomial Pneumonias • Urinary Tract Infections • Intra-abdominal Infections • Gynaecological Infections, such as endometritis.• Skin and Skin Structure Infections • Meningitis • Septicaemia • Cystic fibrosis and chronic lower respiratory tract infections
Dosage and Administration
The dosage and duration of therapy shall be established depending on type and severity of infection and the condition of the patient. The recommended daily dosage is as follows:- 500 mg IV every 8 hours in the treatment of pneumonia, UTI, gynaecological infections such as endometritis, skin and skin structure infections. 1 g IV every 8 hours in the treatment of nosocomial pneumonias, peritonitis, presumed infections in neutropenic patients, septicaemia. In cystic fibrosis, doses up to 2 g every 8 hours have been used; most patients have been treated with 2 g every 8 hours.
No dosage adjustment is required for the elderly with normal renal function or creatinine clearance values above 50 ml/min.
For children over 3 months and up to 12 years of age the recommended dose is 10 to 20 mg/kg every 8 hours depending on type and severity of infection, susceptibility of the pathogen and the condition of the patient. In children over 50 kg weight, adult dosage should be used.
Method of Administrations:
Meropenem IV can be given as an intravenous bolus injection over approximately 5 minutes or by intravenous infusion over approximately 15 to 30 minutes using the specific available presentations. Meropenem IV to be used for bolus intravenous injection should be constituted with sterile Water for Injections (5 ml per 250 mg meropenem). This provides an approximate concentration of 50 mg/ml. Constituted solutions are clear, and colourless or pale yellow. Meropenem IV for intravenous infusion may be constituted with compatible infusion fluids (50 to 200 ml).
Hypersensitivity to any of the ingredients in this product or the cephalosporin class of antibiotics, penicillins or other betalactam antibiotics. / Meropenem is contraindicated in patients who have demonstrated hypersensitivity to this product.
WARNINGS & PRECAUTIONS:
There is some clinical and laboratory evidence of partial cross-allergenicity between other carbapenems and beta-lactam antibiotics, penicillins and cephalosporins. Before initiating therapy with meropenem, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactam antibiotics. Meropenem should be used with caution in patients with such a history. Use in infections caused by methicillin resistant staphylococci is not recommended. Antibiotics should be prescribed with care for individuals with a history of gastro-intestinal complaints, particularly colitis. It is important to consider the diagnosis of pseudomembranous colitis in the case of patients who develop diarrhoea in association with the use of Meropenem.
Efficacy and tolerability in infants under 3 months old have not been established; therefore, Meropenem is not recommended for use below this age. There is no experience in children with altered hepatic or renal function.
Probenecid competes with meropenem for active tubular secretion and thus inhibits the renal excretion, with the effect of increasing the elimination half-life and plasma concentration of meropenem. As the potency and duration of action of Meropenem dosed without probenecid are adequate, the co-administration of probenecid with Meropenem is not recommended. Meropenem may reduce serum valproic acid levels. Subtherapeutic levels may be reached in some patients. Meropenem has been administered concomitantly with other medications without adverse pharmacological interactions.
PREGNANCY AND LACTATION:
Meropenem should not be used in pregnancy unless the potential benefit justifies the potential risk to the foetus. Meropenem is detectable at very low concentrations in animal breast milk. Meropenem should not be used in breast-feeding women unless the potential benefit justifies the potential risk to the baby.
• Local intravenous injection site reactions: inflammation, thrombophlebitis, pain at the site of injection • Systemic allergic reactions: rarely, systemic allergic reactions (hypersensitivity • Skin reactions: rash, pruritus, urticaria. Rarely, severe skin reactions such as Stevens – Johnson syndrome • Gastro-intestinal: abdominal pain, nausea, vomiting, diarrhoea. • Blood: Reversible thrombocythaemia, eosinophilia, thrombocytopenia, leucopenia • Liver function: Increases in serum concentrations of bilirubin, transaminases • Central nervous system: headache, paraesthesiae. • Other: Oral and vaginal candidosis.
OVERDOSE AND TREATMENT:
A few cases of overdose (up to 5 g) have been reported, giving rise to hedache, nausea, epigastric pain and dizziness. The recommended treatment of overdosage consists of eliminating the drug, primarily by the administration of activated charcoal, and giving symptomatic supportive therapy if needed.
Meropenem is a carbapenem antibiotic for parenteral use, that is relatively stable to human dehydropeptidase-1 (DHP-1) and therefore does not require the addition of an inhibitor of DHP-1. Meropenem exerts its bactericidal action by interfering with vital bacterial cell wall synthesis. The ease with which it penetrates bacterial cell walls, its high level of stability to all serine beta-lactamases and its marked affinity for the Penicillin Binding Proteins (PBPs) explain the potent bactericidal action of meropenem against a broad spectrum of aerobic and anaerobic bacteria. Minimum bactericidal concentrations (MBC) are commonly the same as the minimum inhibitory concentrations (MIC). For 76% of the bacteria tested, the MBC:MIC ratios were 2 or less. Meropenem is stable in susceptibility tests and these tests can be performed using normal routine methods. In vitro tests show that meropenem acts synergistically with various antibiotics. It has been demonstrated both in vitro and in vivo that meropenem has a post-antibiotic effect.
The in vitro antibacterial spectrum of meropenem includes the majority of clinically significant Gram-positive and Gram-negative, aerobic and anaerobic strains of bacteria, as shown below:
A 30 minute intravenous infusion of a single dose of Meropenem in healthy volunteers results in peak plasma levels of approximately 11 microgram/ml for the 250 mg dose, 23 microgram/ml for the 500 mg dose and 49 microgram/ml for the 1g dose. A 5 minute intravenous bolus injection of Meropenem in healthy volunteers results in peak plasma levels of approximately 52 microgram/ml for the 500 mg dose and 112 microgram/ml for the 1g dose. Intravenous infusions of 1 g over 2 minutes, 3 minutes and 5 minutes were compared in a three-way crossover trial. After an IV dose of 500 mg, plasma levels of meropenem decline to values of 1 microgram/ml or less, 6 hours after administration. When multiple doses are administered at 8 hourly intervals to subjects with normal renal function, accumulation of meropenem does not occur.
Approximately 70% of the administered dose is recovered as unchanged meropenem in the urine over 12 hours, after which little further urinary excretion is detectable. Urinary concentrations of meropenem in excess of 10 microgram/ml are maintained for up to 5 hours after the administration of a 500 mg dose. No accumulation of meropenem in plasma or urine was observed with regimens using 500 mg administered every 8 hours or 1 g administered every 6 hours in volunteers with normal renal function.
Meropenem penetrates well into most body fluids and tissues including cerebrospinal fluid of patients with bacterial meningitis, achieving concentrations in excess of those required to inhibit most bacteria. Studies in children have shown that the pharmacokinetics of Meropenem in children are similar to those in adults. The elimination half-life for meropenem was approximately 1.5 to 2.3 hours in children under the age of 2 years and the pharmacokinetics are linear over the dose range of 10 to 40 mg/kg. Pharmacokinetic studies in patients with renal insufficiency have shown the plasma clearance of meropenem correlates with creatinine clearance. Dosage adjustments are necessary in subjects with renal impairment. Pharmacokinetic studies in the elderly have shown a reduction in plasma clearance of meropenem which correlated with age-associated reduction in creatinine clearance. Pharmacokinetic studies in patients with liver disease have shown no effects of liver disease on the pharmacokinetics of meropenem.
Store below 25°C , in a dry place. Protect from light.
NATURE AND CONTENTS OF CONTAINER:
A vial of 500 mg/1000 mg is packed in a printed Primary Carton along with the Pack Insert