Porphyromonas asaccharolytica There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another β-lactam. [5] Meropenem is frequently given in the treatment of febrile neutropenia. Dosage adjustment is necessary in patients with creatinine clearance 50 mL/min or less [see Dosage and Administration (2.2), Warnings and Precautions (5.8), Clinical Pharmacology (12.3)]. The overall spectrum is similar to that of imipenem, although meropenem is more active against Enterobacteriaceae and less active against Gram-positive bacteria. Freshly prepared solutions of Meropenem for injection should be used. Approximate Average Concentration (mg/mL), Table 6: Meropenem Pharmacokinetic Parameters in Patients Less Than 3 Months of Age, GA less than 32 weeks PNA less than 2 weeks, GA less than 32 weeks PNA 2 weeks or older, GA 32 weeks or older PNA less than 2 weeks, GA 32 weeks or older PNA 2 weeks or older, Escherichia coli and Pseudomonas aeruginosa, Campylobacter jejuni Citrobacter freundii, Degree of Hearing Loss (in one or both ears), We comply with the HONcode standard for trustworthy health information -, Savior Lifetec Corporation Tainin Branch Injection Plant. Eggerthella lenta, Fusobacterium species 1 gram Injection Vial (NDC 6800-447-58) and packaged in cartons of 10 vials (NDC 68001-447-57). Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. Its structural formula is: Meropenem for injection is a white to pale yellow crystalline powder. Dosage adjustments are necessary in subjects with renal impairment (creatinine clearance 50 mL/min or less) [see Dosage and Administration (2.2), Use In Specific Populations (8.6)]. Dosage adjustment is recommended in patients with advanced age and/or adult patients with creatinine clearance of 50 mL/min or less [see Dosage and Administration (2.2)]. Meropenem is bactericidal except against Listeria monocytogenes, where it is bacteriostatic. Klebsiella pneumoniae Many patients in these trials were severely ill and had multiple background diseases, physiological impairments and were receiving multiple other drug therapies. Meropenem has a niche in its spectrum of coverage. In a peri-postnatal study in rats described in the published literature 2, intravenous Meropenem was administered to dams from Gestation Day 17 until Lactation Day 21 at doses of 240, 500, and 1000 mg/kg/day. Meropenem is the only carbapenem approved for meningitis, for which it can be used as alternative therapy. 3. The success rates in the clinically evaluable patients at the follow-up visit were 86% (225/261) in the Meropenem arm and 83% (238/287) in imipenem-cilastatin arm. There are insufficient human data to establish whether there is a drug-associated risk of major birth defects or miscarriages with Meropenem in pregnant women. In mice and rats, large intravenous doses of Meropenem (2200 mg/kg to 4000 mg/kg) have been associated with ataxia, dyspnea, convulsions, and mortalities. Over time, however, problems such as resistance development and selection of resistant organisms have become apparent. Urinary concentrations of Meropenem in excess of 10 mcg/mL are maintained for up to 5 hours after a 500 mg dose. It is active against Gram-positive and Gram-negative bacteria. Dosing must be adjusted for altered kidney function and for haemofiltration. The largest dose of Meropenem administered in clinical trials has been 2 grams given intravenously every 8 hours. Meropenem has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see Indications and Usage (1)]. The elimination half-life for Meropenem was approximately 1.5 hours in pediatric patients of age 3 months to 2 years. Mechanism of Action. When treating cSSSI caused by P. aeruginosa, a dose of 20 mg/kg (or 1 gram for pediatric patients weighing over 50 kg) every 8 hours is recommended. A pharmacokinetic study with Meropenem in elderly patients with renal impairment showed a reduction in plasma clearance of Meropenem that correlates with age-associated reduction in creatinine clearance. Severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme (EM) and acute generalized exanthematous pustulosis (AGEP) have been reported in patients receiving Meropenem [see Adverse Reactions (6.2) ]. No fetal toxicity or malformations were observed in pregnant rats and Cynomolgus monkeys administered intravenous Meropenem during organogenesis at doses up to 2.4 and 2.3 times the maximum recommended human dose (MRHD) based on body surface area comparison, respectively. Four hundred forty-six patients (397 pediatric patients 3 months to less than 17 years of age) were enrolled in 4 separate clinical trials and randomized to treatment with Meropenem (n=225) at a dose of 40 mg/kg every 8 hours or a comparator drug, i.e., cefotaxime (n=187) or ceftriaxone (n=34), at the approved dosing regimens. (See dosing Table below.). If superinfection does occur during therapy, appropriate measures should be taken. The most common adverse events occurring in greater than 5% of the patients were: headache (7.8%), nausea (7.8%), constipation (7.0%), diarrhea (7.0%), anemia (5.5%), and pain (5.1%). Prevotella intermedia Bactericidal concentrations (defined as a 3 log 10 reduction in cell counts within 12 hours to 24 hours) are typically 1to 2 times the bacteriostatic concentrations of Meropenem, with the exception of Listeria monocytogenes, against which lethal activity is not observed. Discard unused portion, For Intravenous Use Only Its empirical formula is C 17H 25N 3O 5S∙3H 2O with a molecular weight of 437.52. The concomitant use of Meropenem and valproic acid or divalproex sodium is generally not recommended. At this dosage, no adverse pharmacological effects or increased safety risks have been observed. Proteus vulgaris Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. In general, resistance arises due to mutations in penicillin-binding proteins, production of metallo-β-lactamases, or resistance to diffusion across the bacterial outer membrane. Gram-positive bacteria In 2017 the FDA granted approval for the combination of meropenem and vaborbactam to treat adults with complicated urinary tract infections. [1] It is more resistant to breakdown by β-lactamase producing bacteria. Imipenem and meropenem are useful in cases in which P. aeruginosa is a suspected pathogen. Meropenem for injection is indicated for the treatment of complicated skin and skin structure infections (cSSSI) due to Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species . Parabacteroides distasonis Inhibits cell-wall synthesis by binding to penicillin-binding proteins; resistant to most beta-lactamases. It inhibits cell wall synthesis by binding to several penicillin-binding proteins, resulting in defective cell walls & osmotically unstable organisms susceptible to cell lysis. Meropenem for injection should not be mixed with or physically added to solutions containing other drugs. It inhibits bacterial cell wall synthesis like other β-lactam antibiotics. Table 11: Hearing Loss at Post-Therapy in the Evaluable Population Treated with Meropenem. Single dose clear glass vials of Meropenem for injection containing 500 mg or 1 gram (as the trihydrate blended with anhydrous sodium carbonate for re-constitution) of sterile Meropenem powder. Meropenem binds to PBPs 2, 3 and 4 of Escherichia coli and Pseudomonas aeruginosa; and PBPs 1, 2 and 4 of Staphylococcus aureus. Meropenem for injection is indicated for the treatment of complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species . Meropenem for injection should be administered by intravenous infusion over approximately 15 minutes to 30 minutes. [10] Many of these adverse effects were observed in severely ill individuals already taking many medications including vancomycin. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. [2] It was approved for medical use in the United States in 1996. Escherichia coli Mechanism of Action. This is not a list of all drugs or health problems that interact with meropenem. At least 90% of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for Meropenem against isolates of similar genus or organism group. [10] Unlike imipenem, it is stable to dehydropeptidase-1, so can be given without cilastatin. Bacteroides ureolyticus Deaths in 5 patients were assessed as possibly related to Meropenem; 36 (1.2%) patients had Meropenem discontinued because of adverse events. Additional systemic adverse events that were reported with Meropenem and occurring in less than or equal to 1.0% but greater than 0.1% of the patients are listed below within each body system in order of decreasing frequency: Bleeding events were seen as follows: gastrointestinal hemorrhage (0.5%), melena (0.3%), epistaxis (0.2%), hemoperitoneum (0.2%). C. difficile produces toxins A and B which contribute to the development of CDAD. There was no evidence of mutagenic potential found in any of these tests. A comparable number of patients were found to be clinically evaluable (ranging from 61-68%) and with a similar distribution of pathogens isolated on initial CSF culture. Among these are included prior history of seizures or CNS abnormality and concomitant medications with seizure potential. Manufactured by: [1] It is on the World Health Organization's List of Essential Medicines. If an allergic reaction to Meropenem occurs, discontinue the drug immediately. The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. β-Lactams were among the first antimicrobial agents available for the therapy of infectious diseases. In rats administered intravenous Meropenem in late pregnancy and during the lactation period, there were no adverse effects on offspring at doses equivalent to approximately 3.2 times the MRHD based on body surface area comparison (see Data). For pediatric patients (with normal renal function) less than 3 months of age, with complicated intra-abdominal infections, the Meropenem for injection dose is based on gestational age (GA) and postnatal age (PNA). Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. Streptococcus pyogenes 4F., No. [1], Common side effects include nausea, diarrhea, constipation, headache, rash, and pain at the site of injection. [1] It is given by injection into a vein. Meropenem for injection has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis. Blood and Lymphatic System Disorders: agranulocytosis, neutropenia, and leukopenia; a positive direct or indirect Coombs test, and hemolytic anemia. Hafnia alvei, Klebsiella oxytoca Table 5: Meropenem Concentrations in Selected Tissues (Highest Concentrations Reported). Table 1: Recommended Meropenem for Injection Dosage Schedule for Adult Patients with Renal Impairment, Recommended dose (500 mg cSSSI and 1 gram Intra-abdominal). 1. Staphylococcus epidermidis (methicillin-susceptible isolates only), Aeromonas hydrophila Meropenem has been reported to be excreted in human milk. Hypertoxin producing isolates of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. Use of Meropenem in pediatric patients 3 months of age and older with intra-abdominal infections is supported by evidence from adequate and well-controlled studies in adults with additional data from pediatric pharmacokinetics studies and controlled clinical trials in pediatric patients. Meropenem readily penetrates the cell wall of most Gram-positive and Gram-negative bacteria to reach penicillin-binding-protein (PBP) targets. In individuals with normal renal function, rapid renal elimination takes place. Meropenem is a carbapenem antibiotic for parenteral use that exerts its action by interfering with bacterial wall synthesis. Consider symptomatic treatments. Moraxella catarrhalis Meropenem penetrates the cell wall of most gram-positive and gram-negative bacteria to bind penicillin-binding-protein (PBP) targets. Savior Lifetec Corporation Meropenem and its metabolite are readily dialyzable and effectively removed by hemodialysis; however, no information is available on the use of hemodialysis to treat overdosage. [1] Meropenem usually results in bacterial death through blocking their ability to make a cell wall. Currently there is no additional information available to further interpret this observation. See dosing Table 3 below. For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: http://www.fda.gov/STIC. Meropenem for injection (I.V.) A 2014 study looked at cross-reaction between carbapenems and … However, as their use increases and expands into new patient populations, the rate of seizures with these agents may increase. Limited postmarketing experience indicates that if adverse events occur following overdosage, they are consistent with the adverse event profile described in the Adverse Reactions section and are generally mild in severity and resolve on withdrawal or dose reduction. Ertapenem is a 1-beta methyl-carbapenem which is chemically similar to beta lactams. The walls are necessary to protect bacteria from their environment and to keep the contents of the bacterial cell together. Co-administration of probenecid with Meropenem is not recommended. Peptostreptococcus species. The study evaluated Meropenem at doses of 500 mg administered intravenously every 8 hours and imipenem-cilastatin at doses of 500 mg administered intravenously every 8 hours. Campylobacter jejuni Citrobacter freundii When only serum creatinine is available, the following formula (Cockcroft and Gault equation) 1 may be used to estimate creatinine clearance. Clostridium difficile A further 28% is recovered as the microbiologically inactive metabolite. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University.. Bacteroides uniformis Bacteroides thetaiotaomicron It penetrates the bacterial cell wall with its high levels of stability in all serine beta-lactamases and marked affinity for … In fertility studies, intravenous Meropenem was administered to male rats beginning 11 weeks before mating and throughout mating and to female rats from 2 weeks before mating through Gestation Day 7 at doses of 240, 500, and 1000 mg/kg/day. Imipenem was the first carbapenem antibiotic selected for development more than two dec… The study included 510 patients randomized to Meropenem and 527 patients randomized to imipenem-cilastatin. MEDLINE search from 1975 to 1997 and follow-up of references. If you are taking probenecid. Meropenem readily penetrates the cell wall of most gram-positive and gram-negative bacteria to bind penicillin-bindingprotein (PBP) targets. In 2016, a synthetic peptide-conjugated PMO (PPMO) was found to inhibit the expression of New Delhi metallo-beta-lactamase, an enzyme that many drug-resistant bacteria use to destroy carbapenems. Streptococcus agalactiae A similar trend was also seen in the cUTI trial. The clinical efficacy rates by pathogen are provided in Table 8. Propionibacterium acnes. A pharmacokinetic study with Meropenem in elderly patients has shown a reduction in the plasma clearance of Meropenem that correlates with age-associated reduction in creatinine clearance [see Clinical Pharmacology (12.3)]. There is inadequate information regarding the use of Meropenem for injection in patients on hemodialysis or peritoneal dialysis. Meropenem readily penetrates the cell wall of most gram-positive and gram-negative bacteria to bind penicillin-binding-protein (PBP) targets. Meropenem for injection is a sterile, pyrogen-free, synthetic, carbapenem antibacterial for intravenous administration. To compare and contrast imipenem and meropenem in terms of in vitro activity, pharmacokinetics, clinical efficacy and adverse effects. The proportion of patients who discontinued study treatment due to an adverse event was similar for both treatment groups (Meropenem, 2.5% and imipenem-cilastatin, 2.7%). The NOAEL value was considered to be 1000 mg/kg/day (approximately 3.2 times the MRHD based on body surface area comparisons). Table 3: Recommended Meropenem for Injection Dosage Schedule for Pediatric Patients Less than 3 Months of Age with Complicated Intra-abdominal Infections and Normal Renal Function, Infants less than 32 weeks GA and PNA less than 2 weeks, Infants less than 32 weeks GA and PNA 2 weeks and older, Infants 32 weeks and older GA and PNA less than 2 weeks, Infants 32 weeks and older GA and PNA 2 weeks and older. The types of systemic and local adverse events seen in these patients are similar to the adults, with the most common adverse reactions reported as possibly, probably, or definitely related to Meropenem and their rates of occurrence as follows: In the meningitis studies, the rates of seizure activity during therapy were comparable between patients with no CNS abnormalities who received Meropenem and those who received comparator agents (either cefotaxime or ceftriaxone). The solution varies from colorless to yellow depending on the concentration. The following in vitro data are available, but their clinical significance is unknown. The recommended dose of Meropenem for injection is 500 mg given every 8 hours for skin and skin structure infections and 1 gram given every 8 hours for intra-abdominal infections. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Meropenem and any potential adverse effects on the breast-fed child from Meropenem or from the underlying maternal conditions. Carbapenems Mechanism of Action-inhibitors of cell wall synthesis by binding to and inhibiting PBP-2 -Penetrates very well into cell wall -Time dependent Bactericidal. Use of Meropenem in pediatric patients 3 months of age and older with bacterial meningitis is supported by evidence from adequate and well-controlled studies in the pediatric population [see Indications and Usage (1.3), Dosage and Administration (2.3), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.3)]. ... Meropenem and doripenem are thought to be the more potent in vitro agents against gram negative organisms. Meropenem for injection is supplied in 20 mL and 30 mL injection vials containing sufficient Meropenem to deliver 500 mg or 1 gram for intravenous administration, respectively. If you are allergic to meropenem; any part of meropenem; or any other drugs, foods, or substances. One controlled clinical study of complicated intra-abdominal infection was performed in the United States where Meropenem was compared with clindamycin/tobramycin. 12 & 16, Chuangye Rd., Xinshi Dist., Tainan City 74144, Taiwan for In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Last updated on Sep 1, 2020. There are several mechanisms of resistance to carbapenems: 1) decreased permeability of the outer membrane of gram-negative bacteria (due to diminished production of porins) causing reduced bacterial uptake, 2) reduced affinity of the target PBPs, 3) increased expression of efflux pump components, and 4) production of antibacterial drug-destroying enzymes (carbapenemases, metallo-β-lactamases). Using strict evaluability criteria and microbiologic eradication and clinical cures at follow-up which occurred 7 or more days after completion of therapy, the presumptive microbiologic eradication/clinical cure rates and statistical findings are provided in Table 9: Table 9: Presumptive Microbiologic Eradication and Clinical Cure Rates at Test-of-Cure Visit in the Evaluable Population with Complicated Intra-Abdominal Infection. Shake to dissolve and let stand until clear. At the end of a 30-minute intravenous infusion of a single dose of Meropenem for injection in healthy volunteers, mean peak plasma concentrations of Meropenem are approximately 23 mcg/mL (range 14 to 26) for the 500 mg dose and 49 mcg/mL (range 39-58) for the 1 gram dose. No overall differences in safety or effectiveness were observed between these subjects and younger subjects; spontaneous reports and other reported clinical experience have not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. The most common adverse effects are diarrhea (4.8%), nausea and vomiting (3.6%), injection-site inflammation (2.4%), headache (2.3%), rash (1.9%) and thrombophlebitis (0.9%). Two hundred and sixty one (261) patients randomized to Meropenem and 287 patients randomized to imipenem-cilastatin were clinically evaluable. Its strongest affinities are toward PBPs 2, 3 and 4 of Escherichia coli a… Mechanism Of Action. Haemophilus influenzae Bacteroides fragilis The bactericidal action of meropenem results from the inhibition of cell wall synthesis. Review the mechanism of action of ZERBAXA® (ceftolozane and tazobactam), which demonstrated in vitro activity in the presence of certain mechanisms of resistance. Consider administration of antibacterial drugs other than carbapenems to treat infections in patients whose seizures are well controlled on valproic acid or divalproex sodium. Bacteroides vulgatus Case reports in the literature have shown that co-administration of carbapenems, including Meropenem, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. Worldwide post-marketing adverse reactions not otherwise listed in the Adverse Reactions from Clinical Trials section of this prescribing information and reported as possibly, probably, or definitely drug related are listed within each body system in order of decreasing severity. For patients with varying degrees of renal impairment, the incidence of heart failure, kidney failure, seizure and shock reported with Meropenem, increased in patients with moderately severe renal impairment (creatinine clearance 10 to 26 mL/min) [see Dosage and Administration (2.2), Warnings and Precautions (5.9), Use in Specific Populations (8.5), (8.6), Clinical Pharmacology (12.3)]. No information is available on the effects of Meropenem on the breast-fed child or on milk production. The bactericidal activity of meropenem results from the inhibition of cell wallsynthesis. However, the efficacy of Meropenem in treating clinical infections caused by these bacteria have not been established in adequate and well-controlled clinical trials. Close adherence to the recommended dosage regimens is urged, especially in patients with known factors that predispose to convulsive activity. Mechanism of Action: Meropenem is a structural analog of impipenem that is resistant to cleavage by renal dehydropeptidase I. The meropenem component of VABOMERE is a penem antibacterial drug. Pediatric Patients Less Than 3 Months of Age. The bactericidal activity of meropenem results from the inhibition of cell wall synthesis. If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Probenecid competes with Meropenem for active tubular secretion, resulting in increased plasma concentrations of Meropenem. The Meropenem group had a statistically higher number of patients with transient elevation of liver enzymes. Monitoring the renal function is vital because carbapenems should be dose adjusted. The study was open-label, uncontrolled, 98% of the infants received concomitant medications, and the majority of adverse events were reported in neonates less than 32 weeks gestational age and critically ill at baseline, making it difficult to assess the relationship of the adverse events to Meropenem. The dry powder should be stored at controlled room temperature 20º to 25ºC (68º to 77ºF) [see USP]. 12.4 Microbiology. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. 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: 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: insomnia, agitation, delirium, confusion, dizziness, seizure, nervousness, paresthesia, hallucinations, somnolence, anxiety, depression, asthenia [see Warnings and Precautions (5.3) and (5.9)], Respiratory: respiratory disorder, dyspnea, pleural effusion, asthma, cough increased, lung edema, Skin and Appendages: urticaria, sweating, skin ulcer, Urogenital System: dysuria, kidney failure, vaginal moniliasis, urinary incontinence. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with β-lactams. Enterobacter cloacae As with other broad-spectrum antibacterial drugs, prolonged use of Meropenem may result in overgrowth of nonsusceptible organisms. Pseudomonas aeruginosa, Anaerobic bacteria Chemistry and Mechanism of Action Meropenem. Pharmacokinetic studies with Meropenem in patients with renal impairment have shown that the plasma clearance of Meropenem correlates with creatinine clearance. Clostridium perfringens Mechanism of action of meropenem. Re-constitute injection vials (500 mg and 1 gram) with sterile Water for Injection (see Table 4 below). Contents are Sterile, amoxicillin, Keflex, doxycycline, triamcinolone, metronidazole, azithromycin, ciprofloxacin, clindamycin, Augmentin, Flagyl. Solutions prepared for infusion (Meropenem for injection concentrations ranging from 1 mg/mL to 20 mg/mL) re-constituted with Sodium Chloride Injection 0.9% may be stored for 1 hour at up to 25°C (77°F) or 15 hours at up to 5°C (41°F). Meropenem 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 (β)-lactams.
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