(Information for users)
on application of medicinal agent
Trade name: Meropenem
International nonproprietary name: Meropenem
Appearance: a white to pale yellow crystalline powder
Composition: each vial contains
Active substance: Meropenem 500 mg.
Excipients: sodium carbonate.
Dosage form: powder for infusion
Pharmacotherapeutic group: Beta-lactam antibiotic. Carbapenems.
ATX code: J01DH02
It is antibiotic for parenteral administration of carbopenem group, shows antibacterial activity (inhibition of bacterial cell wall synthesis), readilypenetrates through bacterial cell wall, tolerant to most beta-lactamases.
The antibacterial spectrum of Meropenem includes the majority of clinically significant gram-positive and gram-negative aerobic and anaerobic strains of bacteria: Aerobic and facultative Gram-positive microorganisms: Enterococcus faecalis (excluding vancomycin-resistant isolates), Staphylococcus aureus ((beta)-lactamase and non-(beta)-lactamase producing, methicillin-susceptible isolates only), Streptococcus agalactiae, Streptococcus pneumoniae (penicillin-susceptible isolates only), Streptococcus pyogenes, Viridans group streptococci; Aerobic and facultative Gram-negative microorganisms: Escherichia coli, Haemophilus influenzae ((beta)-lactamase and non-(beta)-lactamase-producing), Klebsiella pneumonia, Neisseria meningitides, Pseudomonas aeruginosa, Proteus mirabilis; Anaerobic microorganisms: Bacteroides fragilis, Bacteroides thetaiotaomicron, Peptostreptococcus species.
At least 90% of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoints for meropenem. However, the safety and effectiveness of meropenem in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials: Aerobic and facultative Gram-positive microorganisms:Staphylococcus epidermidis ((beta)-lactamase and non-(beta)-lactamase-producing), methicillin-susceptible isolates only); Aerobic and facultative Gram-negative microorganisms: Acinetobacter species, Aeromonas hydrophila, Campylobacter jejuni, Citrobacter diversus, Citrobacter freundii, Enterobacter cloacae, Haemophilus influenzae (ampicillin-resistant, non-(beta)-lactamase producing isolates [BLNAR isolates]), Hafnia alvei, Klebsiella oxytoca, Moraxella catarrhalis ((beta)-lactamase and non-(beta)-lactamase-producing isolates), Morganella morganii, Pasteurella multocida, Proteus vulgaris, Salmonella species, Serratia marcescens, Shigella species, Yersinia enterocolitica; Anaerobic microorganisms: Bacteroides distasonis, Bacteroides ovatus, Bacteroides uniformis, Bacteroides ureolyticus, Bacteroides vulgates, Clostridium difficile, Clostridium perfringens, Eubacterium lentum, Fusobacterium species, Prevotella bivia, Prevotella intermedia,Prevotella melaninogenica, Porphyromonas asaccharolytica, Propionibacterium acnes.
Meropenem is indicated for the treatment of the following infections in adults and children over 3 months of age:
• Pneumonia, including community acquired pneumonia and nosocomial pneumonia.
• Broncho-pulmonary infections in cystic fibrosis
• Complicated urinary tract infections
• Complicated intra-abdominal infections
• Intra- and post-partum infections
• Complicated skin and soft tissue infections
• Acute bacterial meningitis
Meropenem may be used in the management of neutropenic patients with fever that is suspected to be due to a bacterial infection.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Dosage and administration
Adults: The recommended dose of Meropenem I.V. is 500 mg given every 8 hours for skin and skin structure infections and 1 g given every 8 hours for intra-abdominal infections. Meropenem I.V. should be administered by intravenous infusion over approximately 15 to 30 minutes. Doses of 1 g may also be administered as an intravenous bolus injection (5 to 20 mL) over approximately 3-5 minutes.
Use in Adults with Renal Impairment: Dosage should be reduced in patients with creatinine clearance less than 51 mL/min. creatinine clearance 25-60 ml/min – 0.5-1 g bid; 10-25 ml/min – 250-500 mg bid; less than 10 ml/min – 500 mg every 24 hours.
Use in Pediatric Patients:For pediatric patients from 3 months of age and older, the Meropenem I.V. dose is 10, 20 or 40 mg/kg every 8 hours (maximum dose is 2 g every 8 hours), depending on the type of infection (complicated skin and skin structure, intra-abdominal or meningitis). (See dosing table below.) Pediatric patients weighing over 50 kg should be administered Meropenem I.V. at a dose of 500 mg every 8 hours for complicated skin and skin structure infections, 1 g every 8 hours for intra-abdominal infections and 2 g every 8 hours for meningitis. Meropenem I.V. should be given as intravenous infusion over approximately 15 to 30 minutes or as an intravenous bolus injection (5 to 20 mL) over approximately 3-5 minutes.
There is no experience in pediatric patients with renal impairment.
Body as a Whole: pain, abdominal pain, chest pain, fever, back pain, abdominal enlargement, chills, pelvic pain
Cardiovascular: heart failure, heart arrest, tachycardia, hypertension, myocardial infarction, pulmonary embolus, bradycardia, hypotension, syncope
Digestive System: diarrhea, nausea, vomiting, constipation, oral moniliasis, anorexia, cholestatic jaundice/jaundice, flatulence, ileus, hepatic failure, dyspepsia, intestinal obstruction
Hemic/Lymphatic: anemia, hypochromic anemia, hypervolemia
Metabolic/Nutritional: peripheral edema, hypoxia
Nervous System: headache, insomnia, agitation/delirium, confusion, dizziness, seizure, nervousness, paresthesia, hallucinations, somnolence, anxiety, depression, asthenia
Respiratory: apnea, respiratory disorder, dyspnea, pleural effusion, asthma, cough increased, lung edema
Skin and Appendages: rash, pruiritis, urticaria, sweating, skin ulcer
Urogenital System:dysuria, kidney failure, vaginal moniliasis, urinary incontinence
Adverse Laboratory Changes
Adverse laboratory changes that were reported irrespective of relationship to Meropenem I.V. and occurring in greater than 0.2% of the patients were as follows:
Hepatic:< increased SGPT (ALT), SGOT (AST), alkaline phosphatase, LDH, and bilirubin
Hematologic: increased platelets, increased eosinophils, decreased platelets, decreased hemoglobin, decreased hematocrit, decreased WBC, shortened prothrombin time and shortened partial thromboplastin time, leucocytosis, hypokalemia
Renal: increased creatinine and increased BUN
Urinalysis: presence of red blood cells
Meropenem I.V. is contraindicated in patients with known hypersensitivity to any component of this product or to other drugs in the same class or in patients who have demonstrated anaphylactic reactions to (beta)-lactams, pregnancy, lactation, infants age less than 3 month.
Intentional overdosing of Meropenem I.V. is unlikely, although accidental overdosing might occur if large doses are given to patients with reduced renal function. The largest dose of meropenem administered in clinical trials has been 2 g given intravenously every 8 hours. At this dosage, no adverse pharmacological effects or increased safety risks have been observed.
No specific information is available for the treatment of Meropenem I.V. overdose. In the event of an overdose, Meropenem I.V. should be discontinued and general supportive treatment given until renal elimination takes place. Meropenem and its metabolite are readily dialyzable and effectively removed by hemodialysis; however, no information is available on the use of hemodialysis to treat overdose.
No specific medicinal product interaction studies other than probenecid were conducted.
Probenecid competes with meropenem for active tubular secretion and thus inhibits the renal excretion of meropenem with the effect of increasing the elimination half-life and plasma concentration of meropenem. Caution is required if probenecid is co-administered with meropenem.
The potential effect of meropenem on the protein binding of other medicinal products or metabolism has not been studied. However, the protein binding is so low that no interactions with other compounds would be expected on the basis of this mechanism.
Decreases in blood levels of valproic acid have been reported when it is co-administered with carbapenem agents resulting in a 60-100 % decrease in valproic acid levels in about two days. Due to the rapid onset and the extent of the decrease, co-administration of valproic acid with carbapenem agents is not considered to be manageable and therefore should be avoided
The selection of meropenem to treat an individual patient should take into account the appropriateness of using a carbapenem antibacterial agent based on factors such as severity of the infection, the prevalence of resistance to other suitable antibacterial agents and the risk of selecting for carbapenem-resistant bacteria.
As with all beta-lactam antibiotics, serious and occasionally fatal hypersensitivity reactions have been reported.
Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta-lactam antibiotics may also be hypersensitive to meropenem. Before initiating therapy with meropenem, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactam antibiotics.
If a severe allergic reaction occurs, the medicinal product should be discontinued and appropriate measures taken.
Antibiotic-associated colitis and pseudomembranous colitis have been reported with nearly all anti-bacterial agents, including meropenem, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea during or subsequent to the administration of meropenem. Discontinuation of therapy with meropenem and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given.
Seizures have infrequently been reported during treatment with carbapenems, including meropenem.
Hepatic function should be closely monitored during treatment with meropenem due to the risk of hepatic toxicity (hepatic dysfunction with cholestasis and cytolysis).
Use in patients with liver disease: patients with pre-existing liver disorders should have liver function monitored during treatment with meropenem. There is no dose adjustment necessary.
A positive direct or indirect Coombs test may develop during treatment with meropenem.
The concomitant use of meropenem and valproic acid/sodium valproate is not recommended.
Pregnancy Category B: Reproductive studies have been performed with meropenem in rats at doses of up to 1000 mg/kg/day, and cynomolgus monkeys at doses of up to 360 mg/kg/day (on the basis of AUC comparisons, approximately 1.8 times and 3.7 times, respectively, to the human exposure at the usual dose of 1 g every 8 hours). These studies revealed no evidence of impaired fertility or harm to the fetus due to meropenem, although there were slight changes in fetal body weight at doses of 250 mg/kg/day (on the basis of AUC comparisons, 0.4 times the human exposure at a dose of 1 g every 8 hours) and above in rats. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Freshly prepared solutions of Meropenem I.V. should be used whenever possible. However, constituted solutions of Meropenem I.V. maintain satisfactory potency at controlled room temperature 15-25°C or under refrigeration at 4°C as described in table. Solutions of intravenous Meropenem I.V. should not be frozen.
Water for injection
Sodium Chloride Injection 0.9%
Dextrose Injection 5.0%
Dextrose and Sodium Chloride Injection 5.0%/0.9%
Dextrose and Sodium Chloride Injection 5.0%/0.2%
Potassium Chloride in Dextrose Injection 0.15%/5.0%
Mannitol Injection 2.5%
Dextrose Injection 10.0%
Sodium Bicarbonate Injection 5.0%
Availability of dosage forms
Meropenem is available vials of 500 mg.
Store in protected from light place at temperature not above 25 °C.
Keep away from children.
Do not use after expiration date indicated on the pack.
Pharmacy purchasing terms
Apply on doctor’s prescription.