Tripenem

Tripenem

meropenem

Manufacturer:

Dexa Medica
Full Prescribing Info
Contents
Meropenem.
Description
Each vial of Tripenem contains meropenem bulk equivalent to meropenem anhydrate 0.5 or 1 g.
Action
Pharmacology: 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.
A single set of meropenem susceptibility criteria are recommended based on pharmacokinetics and correlation of clinical and microbiological outcomes with zone diameter and minimum inhibitory concentrations (MIC) of the infecting organisms. (See table as follows).


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The in vitro antibacterial spectrum of meropenem includes the majority of clinically significant gram-positive and -negative, aerobic and anaerobic strains of bacteria as follow:
Gram-Positive Aerobes: Bacillus spp, Corynebacterium diphtheriae, Enterococcus faecalis, Enterococcus liquifaciens, Enterococcus avium, Listeria monocytogenes, Lactobacillus spp, Nocardia asteroides, Staphylococcus aureus (positive and negative penicillinase); coagulase-negative staphylococci which includes Staphylococcus epidermidis, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus cohnii, Staphylococcus xylosus, Staphylococcus warneri, Staphylococcus hominis, Staphylococcus simulans, Staphylococcus intermedius, Staphylococcus sciuri, Staphylococcus lugdunensis, Streptococcus pneumoniae (sensitive and resistant to penicillin), Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus equi, Streptococcus bovis, Streptococcus mitis, Streptococcus mitior, Streptococcus milleri, Streptococcus sanguis, Streptococcus viridans, Streptococcus salivarius, Streptococcus morbillorum, group-G streptococcus, group-F streptococcus, Rhodococcus equi. Gram-Negative Aerobes: Achromobacter xylosoxidans, Acinetobacter anitratus, Acinetobacter lwoffii, Acinetobacter baumannii, Aeromonas hydrophila, Aeromonas sorbria, Aeromonas caviae, Alcaligenes faecalis, Bordetella bronchiseptica, Brucella melitensis, Campylobacter coli, Campylobacter jejuni, Citrobacter freundii, Citrobacter diversus, Citrobacter koseri, Citrobacter amalonaticus, Enterobacter aerogenes, Enterobacter (Pantoea) agglomerans, Enterobacter cloacae, Enterobacter sakazakii, Escherichia coli, Escherichia hermannii, Gardnerella vaginalis, Haemophilus influenzae (including β-lactamase-positive and ampicillin-resistant strains), Haemophilus parainfluenzae, Haemophilus ducreyi, Helicobacter pylori, Neisseria meningitidis, Neisseria gonorrhoeae (including β-lactamase-positive, penicillin-resistant and spectinomycin-resistant strains), Hafnia alvei, Klebsiella pneumoniae, Klebsiella aerogenes, Klebsiella ozaenae, Klebsiella oxytoca, Moraxella (Branhamella) catarrhalis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Proteus penneri, Providencia rettgeri, Providencia stuartii, Providencia alcalifaciens, Pasteurella multocida, Plesiomonas shigelloides, Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas alcaligenes, Burkholderia (Pseudomonas) cepacia, Pseudomonas fluorescens, Pseudomonas stutzeri, Pseudomonas pseudomallei, Pseudomonas acidovorans, Salmonella spp, including Salmonella enteritidis/typhi, Serratia marcescens, Serratia liquefaciens, Serratia rubidaea, Shigella sonnei, Shigella flexneri, Shigella boydii, Shigella dysentriae, Vibrio cholerae, Vibrio parahaemolyticus, Vibrio vulnificus, Yersinia enterocolitica.
Anaerobe Bacteria: Actinomyces odontolyticus, Actinomyces meyeri, Bacteroides-Prevotella-Porphyromonas spp, Bacteroides fragilis, Bacteroides vulgatus, Bacteroides variabilis, Bacteroides pneumosintes, Bacteroides coagulans, Bacteroides uniformis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides eggerthii, Bacteroides capsillosis, Prevotella buccalis, Prevotella corporis, Bacteroides gracilis, Prevotella melaninogenica, Prevotella intermedia, Prevotella bivia, Prevotella splanchnicus, Prevotella oralis, Prevotella disiens, Prevotella rumenicola, Bacteroides ureolyticus, Prevotella oris, Prevotella buccae, Prevotella denticola, Bacteroides levii, Porphyromonas asaccharolytica, Bifidobacterium spp, Bilophila wadsworthia, Clostridium perfringens, Clostridium bifermentans, Clostridium ramosum, Clostridium sporogenes, Clostridium cadaveris, Clostridium sordellii, Clostridium butyricum, Clostridium clostridiiformis, Clostridium innocuum, Clostridium subterminale, Clostridium tertium, Eubacterium lentum, Eubacterium aerofaciens, Fusobacterium mortiferum, Fusobacterium necrophorum, Fusobacterium nucleatum, Fusobacterium varium, Mobiluncus curtisii, Mobiluncus mulieris, Peptostreptococcus anaerobius, Peptostreptococcus micros, Peptostreptococcus saccharolyticus, Peptococcus saccharolyticus, Peptostreptococcus asaccharolyticus, Peptostreptococcus magnus, Peptostreptococcus prevotii, Propionibacterium acnes, Propionibacterium avidum, Propionibacterium granulosum. Stenotrophomonas maltophilia, Enterococcus faecium and methicillin-resistant staphylococci have been found to be resistant to meropenem.
Pharmacokinetics: A 30-min IV infusion of a single dose of meropenem in healthy volunteers results in peak plasma levels of approximately 11 mcg/mL for the 250-mg dose, 23 mcg/mL for the 500-mg dose and 49 mcg/mL for the 1-g dose.
max and AUC. Furthermore, a reduction in plasma clearance from 287 to 205 mL/min for the range of dosage 250 mg to 2 g has been observed.
A 5-min IV bolus injection of meropenem in healthy volunteers results in peak plasma levels of approximately 52 mcg/mL for the 500-mg dose and 112 mcg/mL for the 1-g dose.
Intravenous infusions of 1 g over 2, 3 and 5 mins were compared in a three-way crossover trial. These durations of infusion resulted in peak plasma levels of 110, 91, and 94 mcg/mL, respectively.
After an IV dose of 500 mg, plasma levels of meropenem decline to values of ≤1 mcg/mL, 6 hrs after administration.
When multiple doses are administered at 8 hrly intervals to subjects with normal renal function, accumulation of meropenem does not occur.
In subjects with normal renal function, meropenem's elimination half-life(t½) is approximately 1 hr. Plasma protein binding of meropenem is approximately 2%.
Approximately 70% of the administered dose is recovered as unchanged meropenem in the urine over 12 hrs, after which little further urinary excretion is detectable. Urinary concentrations of meropenem in excess of 10 mcg/mL are maintained for up to 5 hrs 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 hrs or 1 g administered every 6 hrs in volunteers with normal renal function.
The only metabolite of meropenem is microbiologically inactive.
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 t½ for meropenem was approximately 1.5-2.3 hrs in children <2 years and the pharmacokinetics are linear over the dose range of 10-40 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.
Indications/Uses
Single-agent therapy for the treatment, in adults and children, of the following infections caused by single or multiple susceptible strains of the designated microorganisms sensitive to meropenem: Pneumonia and nosocomial pneumonia; urinary tract, intra-abdominal, gynecological infections eg, endometritis; skin and skin structure infections; meningitis; septicemia; bone and joint infections; endocarditis.
Empiric treatment, for presumed infections in adult patients with febrile neutropenia, used as monotherapy or in combination with antiviral or -fungal agents. Meropenem has proved efficacious alone or in combination with other antimicrobial agents in the treatment of polymicrobial infections.
Dosage/Direction for Use
The dosage and duration of therapy shall be established depending on type and severity of infection and the condition of the patients.
Adults: Pneumonia, UTI, Gynecological Infections (eg, endometritis), Skin and Skin Structure Infections: Recommended Daily Dose: 500 mg IV every 8 hrs.
Nosocomial Pneumonias, Peritonitis, Presumed Infections in Neutropenic Patients, Septicemia: Recommended Daily Dose: 1 g IV every 8 hrs.
Meningitis: Recommended Daily Dose: 2 g every 8 hrs.
As with other antibiotics, particular caution is recommended in using meropenem as monotherapy in critically ill patients with known or suspected Pseudomonas aeruginosa lower respiratory tract infection.
Regular sensitivity testing is recommended when treating Pseudomonas aeruginosa infection.
Renal Impairment: Dosage should be reduced in patients with creatinine clearance less than 51 mL/min, as scheduled below:
Creatinine Clearance: 26-50 mL/min: Recommended Dose: 500 mg or 1 g or 2 g every 12 hrs.
10-25 mL/min: Dose: 250 or 500 mg or 1 g (½ of recommended dose); Frequency: Every 12 hrs.
<10 mL/min: 250 mg or 500 mg or 1 g (½ of recommended dose); Frequency: Every 24 hrs.
When only serum creatinine is available, the following formula (Cockcroft and Gault equation) may be used to estimate creatinine clearance.


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Meropenem is cleared by hemodialysis; if continued treatment with meropenem is necessary, it is recommended that the unit (recommended) dose (based on the type and severity of infection) is administered at the completion of the hemodialysis procedure to restore therapeutically effective plasma concentrations.
There is no experience with the use of meropenem in patients under peritoneal dialysis.
Hepatic Insufficiency: No dosage adjustment is required in patients with hepatic insufficiency.
Elderly: No dosage adjustment is required for the elderly with normal renal function or creatinine clearance values >50 mL/min.
Children 3 Months to 12 Years: The recommended dose is 10-20 mg/kg every 8 hrs 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.
Meningitis: The recommended dose is 40 mg/kg every 8 hrs.
Administration: Adults: Tripenem IV can be given as an IV bolus injection over approximately 5 min or by IV infusion over approximately 15-30 min using the specific available presentations.
Tripenem IV to be used for IV bolus injection should be constituted with sterile water for injections (5 mL per meropenem 250 mg). This provides an approximate concentration of 50 mg/mL. Constituted solutions are clear and colourless or pale yellow.
Tripenem IV for IV infusion may be constituted with compatible infusion fluids (50-200 mL).
Overdosage
Accidental overdosage could occur during therapy, particularly in patients with renal impairment. Management of overdose is symptomatic. In the event of an overdose, Tripenem should be discontinued and general supportive treatment given until renal elimination takes place. In normal individuals, rapid renal elimination will occur; in subjects with renal impairment, haemodialysis will remove meropenem and its metabolite.
Contraindications
History of hypersensitivity to meropenem.
Special Precautions
There is some clinical and laboratory evidence of partial cross-allergenicity between other carbapenems and β-lactam antibiotics, penicillins and cephalosporins. As with all β-lactam antibiotics, rare hypersensitivity reactions have been reported. Before initiating therapy with meropenem, careful inquiry should be made concerning previous hypersensitivity reactions to β-lactam antibiotics. Meropenem should be used with caution in patients with such a history. If an allergic reaction to meropenem occurs, treatment should be discontinued and appropriate measures taken.
As with other antibiotics, overgrowth of nonsusceptible organisms may occur and, therefore, continuous monitoring of each patient is necessary.
Patients with Hepatic Impairment: Use of meropenem in patients with hepatic disease should be made with careful monitoring of transaminase and bilirubin levels.
Use in infections caused by methicillin-resistant staphylococci is not recommended.
Rarely, pseudomembranous colitis has been reported on meropenem as with practically all antibiotics and may vary in severity from slight to life-threatening. Therefore, antibiotics should be prescribed with care for individuals with a history of gastrointestinal complaints, particularly colitis. It is important to consider the diagnosis of pseudomembranous colitis in the case of patients who develop diarrhea in association with the use of meropenem. Although studies indicate that a toxin produced by Clostridium difficile is one of the main causes of antibiotic-associated colitis, other causes should be considered.
The co-administration of meropenem with potentially nephrotoxic drugs should be considered with caution.
Seizures and other central nervous system (CNS) adverse experiences have been reported during treatment with meropenem. These experiences have occurred most commonly in patients with CNS disorders (eg, brain lesions or history of seizures) or with bacterial meningitis and/or compromised renal function.
Effects on the Ability to Drive and Operate Machinery: No data are available, but it is not anticipated that meropenem will affect the ability to drive and use machines.
Use in pregnancy & lactation: Pregnancy Category B: The safety of meropenem in human pregnancy has not been evaluated. Animal studies have not shown any adverse effect on the developing fetus. The only adverse effect observed in animal reproductive studies was an increased incidence of abortions in monkeys at 13 times the expected exposure in man. Meropenem should not be used in pregnancy unless the potential benefit justifies the potential risk to the fetus. In every case, it should be used under the direct supervision of the physician.
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.
Use in children: Efficacy and tolerability in infants <3 months 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.
Adverse Reactions
Serious adverse events are rare. From clinical trials, the following adverse events were reported:
Local Reaction on Injection Site: Inflammation, thrombophlebitis, pain at injection site. Rarely, severe skin reactions eg, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis have been observed.
Systemic Allergic Reaction: Rarely, systemic allergic reactions (hypersensitivity) may occur following administration of meropenem. These reactions may include angioedema and anaphylactic manifestations eg, shock, hypotension and respiratory depression.
Gastrointestinal Tract Reactions: Abdominal pain, nausea, vomiting, diarrhea, pseudomembranous colitis.
Hematology Effect: Reversible thrombocythaemia, eosinophilia, thrombocytopenia, leucopenia and neutropenia. A positive direct or indirect Coomb's test may develop in some subjects; there have been reports of reduction in partial thromboplastin time.
Liver Function: Increases in serum concentrations of bilirubin, transaminases, alkaline phosphatase and lactic dehydrogenase alone or in combination have been reported.
Central Nervous System: Headache, paraesthesia. Infrequent convulsion have been reported although a causal link with meropenem has not been established.
Others: Oral and vaginal candidosis.
Drug Interactions
Probenecid: Competes with meropenem for active tubular secretion and thus inhibits renal excretion, with the effect of increasing the elimination t½ 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.
The potential effect of meropenem on the protein-binding of other drugs or metabolism has not been studied. The protein-binding of meropenem is low (approximately 2%), therefore, interaction with other compounds based on displacement of drug-binding from plasma protein is not expected.
Meropenem may reduce serum valproic acid levels. Subtherapeutic levels may be reached in some patients.
Storage
Store at a temperature below 30°C. Protect from the light.
MIMS Class
ATC Classification
J01DH02 - meropenem ; Belongs to the class of carbapenems. Used in the systemic treatment of infections.
Presentation/Packing
Inj (vial) 0.5 g x 1's. 1 g x 1's.
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