Meningitis: What It Is and How to Avoid It Watch Video

Generic Name: Meropenem
Class: Carbapenems
Chemical Name: [4R-[3(3S*,5S*),4α,5β,6β(R)]]-3-[[5- [(Dimethylamino)carbonyl] - 3 - pyrrolidinyl]thio] - 6 - (1 - hydroxyethyl) - 4 - methyl - 7 - oxo - 1 - azabicyclo[3.2.0]hept - 2 - ene - 2 - carboxylic acid trihydrate
Molecular Formula: C17H25N3O5S•3H2OC17H25N3O5S
CAS Number: 119478-56-7

Introduction

Antibacterial; carbapenem β-lactam antibiotic.1 2 3

Uses for Merrem

Intra-abdominal Tract Infections

Treatment of intra-abdominal infections (complicated appendicitis, peritonitis) caused by susceptible viridans streptococci, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, or Peptostreptococcus.1 2 3 4 6 7 9 10 12 24 28 43

Has a broad spectrum of antibacterial activity against both aerobes and anaerobes; may be used empirically to treat intra-abdominal infections before identification of the causative organism.1 2 6 7 10

For immunosuppressed patients or those with severe intra-abdominal infections, IDSA recommends an initial empiric regimen with broad spectrum of activity such as meropenem or imipenem; a third or fourth generation cephalosporin (cefepime, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone) in conjunction with metronidazole; ciprofloxacin in conjunction with metronidazole; piperacillin-tazobactam; or aztreonam in conjunction with metronidazole.28 For mild to moderate community-acquired intra-abdominal infections, IDSA recommends an initial empiric regimen with narrower spectrum of activity such as ampicillin-sulbactam; cefazolin or cefuroxime in conjunction with metronidazole; ticarcillin-clavulanate; ertapenem; or a fluoroquinolone (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin) in conjunction with metronidazole.28

For postoperative (nosocomial) intra-abdominal infections, IDSA recommends the empiric regimen be selected based on local nosocomial susceptibility patterns; these infections usually require treatment with multiple-drug regimens and often involve resistant organisms.28

Meningitis

Treatment of bacterial meningitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae (including β-lactamase-producing strains), or Neisseria meningitidis in children ≥3 months of age.1 2 8 10 Also has been used for treatment of meningitis in adults.29 46

Efficacy for treatment of meningitis caused by highly penicillin- or cephalosporin-resistant S. pneumoniae has not been established.1 29 44 45

Can be used as monotherapy for meningitis caused by susceptible bacteria.1 Although not usually considered initial drug of choice,24 25 29 30 recommended as an alternative in children and adults for treatment of meningitis caused by S. pneumoniae or H. influenzae.24 25 29 30 Also may be useful for meningitis caused by susceptible gram-negative bacteria (e.g., Enterobacter, Citrobacter, Serratia marcescens) resistant to usually recommended regimens.29

Slideshow: Flashback: FDA Drug Approvals 2013

Respiratory Tract Infections

Treatment of respiratory tract infections, including community-acquired pneumonia (CAP) and nosocomial pneumonia.19 20 21 22 23 24 26 27

ATS, IDSA, and others consider meropenem an alternative, not a drug of first choice, for empiric treatment of CAP caused by S. pneumoniae.19 20 23 26 ATS and IDSA suggest the drug be reserved for when CAP may be caused by Ps. aeruginosa,20 23 Klebsiella,23 or other gram-negative bacteria.23 Also may be considered when anaerobes are known or suspected to be involved.19

A drug of choice for empiric treatment of nosocomial pneumonia.24 26 ATS, IDSA, and others recommend an antipseudomonal cephalosporin (cefepime, ceftazidime), antipseudomonal penicillin (piperacillin-tazobactam, ticarcillin-clavulanate), or antipseudomonal carbapenem (imipenem or meropenem) for initial therapy of hospital-acquired pneumonia, ventilator-associated pneumonia, or health-care associated pneumonia because these drugs have broad spectrum of activity against gram-positive, gram-negative, and anaerobic bacteria.24 26 27 In severely ill patients or in those with late-onset disease or risk factors for multidrug-resistant bacteria, initial regimen should also include an aminoglycoside (amikacin, gentamicin, tobramycin) or antipseudomonal fluoroquinolone (ciprofloxacin or levofloxacin) to improve coverage against Pseudomonas.24 26 In hospitals where oxacillin-resistant (methicillin-resistant) Staphylococcus are common or if there are risk factors for these strains, the initial regimen also should include vancomycin or linezolid.24 26 27 In hospitals where multidrug-resistant Ps. aeruginosa are frequent causes of nosocomial pneumonia, an initial regimen of cefepime or a carbapenem (imipenem or meropenem) in conjunction with an aminoglycoside is recommended.26 54

Septicemia

Treatment of septicemia caused by susceptible bacteria.24

Skin and Skin Structure Infections

Treatment of complicated skin and skin structure infections caused by susceptible S. aureus (including β-lactamase-producing strains, but not oxacillin-resistant [methicillin-resistant] strains), S. pyogenes (group A β-hemolytic streptococci), S. agalactiae (group B streptococci), viridans streptococci, Enterococcus faecalis (not vancomycin-resistant strains), Ps. aeruginosa, E. coli, Proteus mirabilis, B. fragilis, or Peptostreptococcus.1

Urinary Tract Infections

Treatment of complicated urinary tract infections caused by susceptible bacteria.38

Acinetobacter Infections

Treatment of infections caused by Acinetobacter;24 a drug of choice used with or without an aminoglycoside.24

Anthrax

Recommended as one of several anti-infectives that can be included in multiple-drug regimens used for the treatment of anthrax, including inhalational anthrax and anthrax meningitis.31 39

Has in vitro activity against Bacillus anthracis; data not available regarding in vivo activity.40

Bacillus Infections

Treatment of infections caused by Bacillus cereus.24 Vancomycin considered drug of choice; carbapenems (imipenem or meropenem) or clindamycin are alternatives.24

Burkholderia Infections

Treatment of melioidosis caused by Burkholderia pseudomallei.24 31 32 33 34 Severe illness requires an initial parenteral regimen of ceftazidime, imipenem, or meropenem (with or without concomitant co-trimoxazole or doxycycline), followed by a prolonged oral maintenance regimen of co-trimoxazole in conjunction with doxycycline or amoxicillin-clavulanate.31 34

Treatment of glanders caused by B. mallei.31 34 Experience is limited regarding treatment of human cases; optimum regimens not identified.31 34 Some clinicians suggest streptomycin used in conjunction with tetracycline or chloramphenicol or imipenem monotherapy.24 Others suggest that, pending results of in vitro susceptibility tests, regimens used for treatment of melioidosis can be used for initial empiric treatment of glanders.34

The US Army Medical Research Institute of Infectious Diseases (USAMRIID) and European Commission’s Task Force on Biological and Chemical Agent Threats (BICHAT) state that the same treatment regimens recommended for naturally occurring melioidosis or glanders should be used if these Burkholderia infections occur in the context of biologic warfare or bioterrorism.31 34 These experts suggest that postexposure prophylaxis with doxycycline or co-trimoxazole for ≥10 days can be attempted in such situations, but is of unproven benefit.31 34

Campylobacter Infections

Treatment of systemic infections caused by Campylobacter fetus;24 a drug of choice.24

Capnocytophaga Infections

Treatment of infections caused by Capnocytophaga canimorsus.24

Optimum regimens for treatment of Capnocytophaga infections not identified; some clinicians recommend use of penicillin G or, alternatively, a third generation cephalosporin (cefotaxime, ceftizoxime, ceftriaxone), a carbapenem (imipenem or meropenem), vancomycin, a fluoroquinolone, or clindamycin.24

Clostridium Infections

Treatment of infections caused by Clostridium perfringens; alternative to penicillin G for those with penicillin hypersensitivity or for polymicrobial infections.24 25

Nocardia Infections

Treatment of infections caused by Nocardia.24 25 Co-trimoxazole usually drug of first choice;24 alternatives include sulfisoxazole, a tetracycline (e.g., doxycycline, minocycline), a carbapenem (imipenem or meropenem), amikacin, ceftriaxone, amoxicillin-clavulanate, cycloserine, or linezolid.24 25

Rhodococcus Infections

Treatment of infections caused by Rhodococcus equi.24 Optimum regimens not identified; combination regimens usually recommended, including vancomycin given with a fluoroquinolone, rifampin, a carbapenem (imipenem or meropenem), or amikacin.24

Empiric Therapy in Febrile Neutropenic Patients

Empiric anti-infective therapy of presumed bacterial infections in febrile neutropenic patients.14 24 Used alone or in conjunction with other anti-infectives.14 24

Consult published protocols for the treatment of infections in febrile neutropenic patients for specific recommendations regarding selection of the initial empiric regimen, when to change the initial regimen, possible subsequent regimens, and duration of therapy in these patients.14 Consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients also is advised.14

Merrem Dosage and Administration

Administration

Administer by IV injection or infusion.1

For solution and drug compatibility information, see Compatibility under Stability.

IV Injection

Reconstitution

Reconstitute single-use vials containing 500 mg or 1 g with 10 or 20 mL, respectively, of sterile water for injection to provide a solution containing approximately 50 mg/mL.1 The vial should be shaken until dissolution occurs and then allowed to stand until the solution is clear.1

Rate of Administration

The appropriate dose of reconstituted solution should be injected over a period of 3–5 minutes.1

IV Infusion

Reconstitution and Dilution

Reconstitute infusion vials containing 500 mg or 1 g with a compatible IV solution (e.g., 0.9% sodium chloride, 5% dextrose) to provide solutions containing approximately 2.5–50 mg/mL.1 Alternatively, reconstitute vials containing 500 mg or 1 g with 10 or 20 mL, respectively, of sterile water for injection and then further dilute in a compatible IV.1

Rate of Administration

Infuse IV over 15–30 minutes.1

Dosage

Available as the trihydrate; dosage expressed in terms of anhydrous meropenem.13

To minimize risk of seizures, closely adhere to dosage recommendations, especially in patients with factors known to predispose to seizure activity; dosage adjustment recommended for patients with advanced age and/or renal impairment.1

Anticonvulsant therapy should be continued in patients with existing seizure disorders.1 (See CNS Effects under Cautions.)

Pediatric Patients

Intra-abdominal Infections
IV

Children ≥3 months of age weighing ≤50 kg: 20 mg/kg (up to 1 g) every 8 hours.1 2

Children ≥3 months weighing >50 kg: 1 g every 8 hours.1

Meningitis
IV

Children ≥3 months of age weighing ≤50 kg: 40 mg/kg (up to 2 g) every 8 hours.1 2

Children ≥3 months weighing >50 kg: 2 g every 8 hours.1

Skin and Skin Structure Infections
IV

Children ≥3 months of age weighing ≤50 kg: 10 mg/kg (up to 500 mg) every 8 hours.1

Children ≥3 months weighing >50 kg: 500 mg every 8 hours.1

Burkholderia Infections
Initial Treatment of Severe Disease
IV

Children ≥3 months of age weighing ≤40 kg: 10–20 mg/kg every 8 hours.34

Children ≥3 months weighing >40 kg: use adult dosage.34

Initial IV regimen continued for ≥14 days and until clinical improvement occurs.31 34 When appropriate, switch to a prolonged oral maintenance regimen (e.g., co-trimoxazole with doxycycline, amoxicillin-clavulanate).31 34 Lifelong follow-up recommended for all patients to identify relapse.31

Adults

Intra-abdominal Infections
IV

1 g every 8 hours.1

Meningitis
IV

6 g daily.29 Dosage of 40 mg/kg every 8 hours (up to 6 g daily) has been used in conjunction with ceftriaxone or cefotaxime.46

Respiratory Tract Infections
Nosocomial Pneumonia
IV

1 g every 8 hours.27

Skin and Skin Structure Infections
IV

500 mg every 8 hours.1

Burkholderia Infections
Initial Treatment of Severe Disease
IV

25 mg/kg IV every 8 hours (up to 6 g daily) recommended by USAMRIID and others; concomitant co-trimoxazole (8 mg/kg of trimethoprim daily given IV in 4 divided doses) also may be indicated.31 32 33 Other clinicians recommend 0.5–1 g every 8 hours with or without co-trimoxazole.34

Initial IV regimen continued for ≥14 days and until clinical improvement occurs.31 34 When appropriate, switch to a prolonged oral maintenance regimen (e.g., co-trimoxazole with doxycycline, amoxicillin-clavulanate).31 34 Lifelong follow-up recommended for all patients to identify relapse.31

Prescribing Limits

Pediatric Patients

IV

2 g every 8 hours.1

Special Populations

Hepatic Impairment

Dosage adjustments not required.1

Renal Impairment

Dosage adjustments recommended in adults with Clcr ≤50 mL/minute.1 Data insufficient to make dosage recommendations for pediatric patients with renal impairment.1

Dosage for Adults with Renal Impairment1

Clcr (mL/min)

Daily Dosage

26–50

usual dose every 12 hours

10–25

50% of usual dose every 12 hours

<10

50% of usual dose once every 24 hours

Manufacturer states data insufficient to make dosage recommendations in patients undergoing hemodialysis or peritoneal dialysis.1 Meropenem removed by hemodialysis; some clinicians suggest that supplemental doses be given after each hemodialysis session.47 48 Also removed by various forms of continuous renal replacement therapy, including continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous hemofiltration (CVVHF), and continuous ambulatory peritoneal dialysis (CAPD).49 50 51 52 53 To avoid inadequate concentrations in anuric patients undergoing these procedures, some clinicians suggest dosage adjustments are necessary and should be based on characteristics of the specific procedure (e.g., filter or membrane type, amount of filtrate produced, dialysate flow rate).49 50 51 52 53

Geriatric Patients

No dosage adjustments except those related to renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Cautions for Merrem

Contraindications

  • Known hypersensitivity to meropenem, other carbapenems, or any ingredient in the formulation.1

  • History of anaphylactic reaction to β-lactams.1

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible organism.1 Careful observation of the patient is essential.1 Institute appropriate therapy if superinfection occurs.1

Treatment with anti-infectives may permit overgrowth of clostridia.1 Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.1

Some mild cases of C. difficile-associated diarrhea and colitis may respond to discontinuance alone.1 56 57 58 59 Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.1 56 57 58 59

CNS Effects

Seizures and other CNS effects reported, especially in those with CNS disorders (e.g., brain lesions, history of seizures) or with bacterial meningitis and/or renal impairment.1

Do not exceed recommended dosage, especially in those with known factors that predispose to seizures.1 Anticonvulsant therapy should be continued in those with known seizure disorders.1

If focal tremors, myoclonus, or seizures occur, evaluate the patient neurologically, initiate anticonvulsant therapy if necessary, and determine whether meropenem dosage should be decreased or the drug discontinued.1

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions (e.g., anaphylaxis) reported with β-lactams.1

If hypersensitivity occurs, discontinue meropenem and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen).1

Cross-hypersensitivity

Partial cross-allergenicity among β-lactam antibiotics, including penicillins, cephalosporins, and other β-lactams.1

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to meropenem, cephalosporins, penicillins, or other drugs.1

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of meropenem and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1

Laboratory Monitoring

Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.1

Sodium Content

Each g of meropenem contains 3.92 mEq (90.2 mg) of sodium as sodium carbonate.1

Specific Populations

Pregnancy

Category B.1

Lactation

Not known whether distributed into milk.1 Use with caution.1

Pediatric Use

Safety and efficacy not established in children <3 months of age.1

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1

Substantially eliminated by kidneys; risk of toxicity may be greater in patients with impaired renal function.1 Select dosage with caution and assess renal function periodically since geriatric patients are more likely to have renal impairment.1

No dosage adjustments except those related to renal function.1 (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Pharmacokinetics not affected by hepatic impairment; dosage adjustments not required.1

Renal Impairment

Decreased clearance.1 Dosage adjustments recommended in patients with Clcr ≤50 mL/minute.1 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (diarrhea, nausea, vomiting, constipation), local reactions (pain and inflammation at injection site, phlebitis/thrombophlebitis), headache, anemia, rash, pruritus, sepsis, apnea, shock, glossitis, oral candidiasis.1

Interactions for Merrem

Specific Drugs

Drug

Interaction

Comments

Aminoglycosides

In vitro evidence of synergistic antibacterial effects against Ps. aeruginosa1

Probenecid

Decreased renal tubular secretion of meropenem; increased meropenem concentrations and AUC and prolonged half-life1

Concomitant use not recommended1

Valproic acid

Valproic serum concentrations may be decreased to subtherapeutic concentrations; possible increased risk of seizures1 35 36 37

Use concomitantly with caution36 55

Merrem Pharmacokinetics

Distribution

Extent

Well distributed into body tissues and fluids, including bronchial mucosa, lung, bile, gynecologic tissue (endometrium, myometrium, ovary, cervix, fallopian tube), muscle, heart valves, skin, and interstitial and peritoneal fluid.1

Distributed into CSF.1

Plasma Protein Binding

Approximately 2%.1

Elimination

Metabolism

Partially metabolized; at least 1 metabolite is microbiologically active.1

Elimination Route

Eliminated in urine as unchanged drug.1 70% of an IV dose eliminated in urine as unchanged drug.1

Half-life

Adults with normal renal function: approximately 1 hour.1

Children 3 months to 2 years of age: approximately 1.5 hours.1

Special Populations

Pharmacokinetics not affected by hepatic impairment.1

Decreased clearance in patients with renal impairment.1

Stability

Storage

Parenteral

Powder for Injection

20–25°C.1 Do not freeze reconstituted or diluted solutions.1

Solutions for IV injection containing approximately 50 mg/mL prepared using water for injection are stable for 2 hours at 15–25°C or 12 hours at 4°C.1

Solutions for IV infusion containing 2.5–50 mg/mL prepared using 0.9% sodium chloride are stable for up to 2 hours at 15–25°C or 18 hours at 4°C; those prepared using 5% dextrose are stable for up to 1 hour at 15–25°C or 8 hours at 4°C.1 1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Incompatible (by conventional definition, but recommended for dilution with use in shorter periods of time)

Dextrose 5% with potassium chloride 0.15%

Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% with sodium bicarbonate 0.02%

Dextrose 2.5% in sodium chloride 0.45%

Dextrose 5% in sodium chloride 0.2 or 0.9%

Dextrose 5 or 10% in water

Mannitol 2.5 or 10%

Normosol M with dextrose 5%

Ringer’s injection

Ringer’s injection, lactated

Sodium bicarbonate 5%

Sodium chloride 0.45%

Sodium lactate (1/6) M

Variable

Sodium chloride 0.9%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Aminophylline

Atropine sulfate

Dexamethasone sodium phosphate

Dobutamine HCl

Dopamine HCl

Enalaprilat

Fluconazole

Furosemide

Gentamicin sulfate

Heparin sodium

Insulin, regular

Magnesium sulfate

Metoclopramide HCl

Morphine sulfate

Norepinephrine bitartrate

Phenobarbital sodium

Ranitidine HCl

Vancomycin HCl

Incompatible

Amphotericin B

Multivitamins

Variable

Acyclovir sodium

Doxycycline hyclate

Ondansetron HCl

Zidovudine

Y-Site CompatibilityHID

Compatible

Aminophylline

Anidulafungin

Atropine sulfate

Caspofungin acetate

Cyclosporine

Dexamethasone sodium phosphate

Digoxin

Diphenhydramine HCl

Docetaxel

Enalaprilat

Fluconazole

Furosemide

Gentamicin sulfate

Heparin sodium

Insulin, regular

Linezolid

Metoclopramide HCl

Milrinone lactate

Morphine sulfate

Norepinephrine bitartrate

Phenobarbital sodium

Potassium chloride

Telavancin HCl

Vancomycin HCl

Vasopressin

Incompatible

Amphotericin B

Diazepam

Variable

Acyclovir sodium

Calcium gluconate

Doxycycline hyclate

Ondansetron HCl

Zidovudine

Actions and Spectrum

  • Synthetic carbapenem β-lactam antibiotic; structurally and pharmacologically related to imipenem and ertapenem.1 2 3

  • Usually bactericidal in action.1

  • Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.1

  • Spectrum of activity includes many gram-positive and -negative aerobic bacteria and some gram-positive and -negative anaerobic bacteria.1 Stable in the presence of a variety of β-lactamases (including penicillinases, cephalosporinases, and extended-spectrum β-lactamases).1

  • Gram-positive aerobes: Active in vitro and in clinical infections against Streptococcus pneumoniae (penicillin-susceptible strains only) and viridans streptococci.1 Also active in vitro against Staphylococcus aureus and S. epidermidis.1 Oxacillin-resistant (methicillin-resistant) staphylococci are resistant.1

  • Gram-negative aerobes: Active in vitro and in clinical infections against Escherichia coli, Haemophilus influenzae (including β-lactamase-producing strains), Klebsiella pneumoniae, Neisseria meningitidis and Pseudomonas aeruginosa.1 Also active in vitro against Acinetobacter, Aeromonas hydrophila, Campylobacter jejuni, Citrobacter, Enterobacter, H. influenzae (ampicillin-resistant, non-β-lactamase-producing strains; BLNAR), Havnia alvei, K. oxytoca, Moraxella catarrhalis, Morganella morganii, Pasteurella multocida, Proteus mirabilis, P. vulgaris, Salmonella, Shigella, Serratia marcescens, and Yersinia enterocolitica.1

  • Anaerobes: Active in vitro and in clinical infections against Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus.1 Also active in vitro against B. distasonis, B. ovatus, B. uniformis, B. ureolyticus, B. vulgatus, Clostridium difficile, C. perfringens, Eubacterium lentum, Fusobacterium, Prevotella bivia, P. intermedia, P. melaninogenica, Porphyromonas asaccharolytica, and Propionibacterium acnes.1

Advice to Patients

  • Advise patients that antibacterials (including meropenem) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1

  • Importance of completing full course of therapy, even if feeling better after a few days.1

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with meropenem or other antibacterials in the future.1

  • Importance of informing clinicians of other medical conditions, including history of seizures.1

  • Importance of discontinuing therapy and informing clinician if an allergic or hypersensitivity reaction occurs.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Meropenem (Trihydrate)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use only

500 mg (of anhydrous meropenem)

Merrem I.V.

AstraZeneca

1 g (of anhydrous meropenem)

Merrem I.V.

AstraZeneca

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Meropenem 500MG Solution (SANDOZ): 1/$29.99 or 3/$79.97

Merrem 1GM Solution (ASTRAZENECA): 1/$79.56 or 5/$386.17

Merrem 500MG Solution (ASTRAZENECA): 1/$39.99 or 10/$365.99

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 10, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. AstraZeneca Pharmaceuticals. Merrem IV (meropenem) for injection for intravenous use only prescribing information. Wilmington, DE; 2005 May.

2. Wiseman LR, Wagstaff AJ, Brogden RN et al. Meropenem: a review of its antibacterial activity, pharmacokinetic properties and clinical efficacy. Drugs. 1995; 50:73-101. [PubMed 7588092]

3. Pryka RD, Haig GM. Meropenem: a new carbapenem antimicrobial. Ann Pharmacother. 1994; 28:1045-54. [IDIS 335809] [PubMed 7803882]

4. Condon RE, Walker AP, Sirinek KR et al. Meropenem versus tobramycin plus clindamycin for treatment of intraabdominal infections: results of a prospective, randomized, double-blind clinical trial. Clin Infect Dis. 1995; 21:544-50. [IDIS 354815] [PubMed 8527541]

5. Brismar B, Malmborg AS, Tunevall G et al. Meropenem versus imipenem/cilastatin in the treatment of intra-abdominal infections. J Antimicrob Chemother. 1995; 35:139-48. [IDIS 343753] [PubMed 7768761]

6. Geroulanos SJ and the Meropenem Study Group. Meropenem versus imipenem/cilastatin in intra-abdominal infections requiring surgery. J Antimicrob Chemother. 1995; 36(Suppl A):191-205. [IDIS 353291] [PubMed 8543495]

7. Huizinga WKJ, Warren BL, Baker LW et al. Antibiotic monotherapy with meropenem in the surgical management of intra-abdominal infections. J Antimicrob Chemother. 1995; 36(Suppl A):179-89. [IDIS 353290] [PubMed 8543493]

8. Klugman KP, Dagan R, and the Meropenem Meningitis Study Group. Randomized comparison of meropenem with cefotaxime for treatment of bacterial meningitis. Antimicrob Agents Chemother. 1995; 39:1140-6. [IDIS 346314] [PubMed 7625802]

9. Anonymous. Meropenem—an advatageous antibiotic? Drug and Therapeutics Bulletin. 1996; 34:53-5.

10. Bradley JS, Faulkner KL, Klugman KP. Efficacy, safety and tolerability of meropenem as empiric antibiotic therapy in hospitalized pediatric patients. Pediatr Infect Dis J. 1996; 15:749-57. [IDIS 372345] [PubMed 8858694]

11. Fukasawa M, Sumita Y, Harabe ET et al. Stability of meropenem and effect of 1β- methyl substitution on its stability in the presence of renal dehydropeptidase I. Antimicrob Agents Chemother. 1992; 36:1577-9. [PubMed 1510457]

12. Briceland LL, Tobin EH. Focus on meropenem: a broad-spectrum parenteral carbapenem antimicrobial agent. Formulary. 1996; 31:759-74.

13. Zeneca Pharmaceuticals, Wilmington, DE: Personal communication.

14. Hughes WT, Armstrong D, Bodey GP et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002; 34:730-51. [IDIS 479956] [PubMed 11850858]

15. Pizzo PA. Management of fever in patients with cancer and treatment-induced neutropenia. N Engl J Med. 1993; 328:1323-32. [IDIS 313154] [PubMed 8469254]

16. Ramphal R, Gucalp R, Rotstein C et al. Clinical experience with single agent and combination regimens in the management of infection in the febrile neutropenic patient. Am J Med. 1996; 100(Suppl 6A):83S-89S. [IDIS 370422] [PubMed 8678102]

17. Viscoli C. The evolution of the empirical management of fever and neutropenia in cancer patients. J Antimicrob Chemother. 1998; 41(Suppl D):65-80. [IDIS 409104] [PubMed 9688453]

18. Rolston KV. Expanding the options for risk-based therapy in febrile neutropenia. Diagn Microbiol Infect Dis. 1998; 31:411-6. [PubMed 9635917]

19. Bartlett JG, Dowell SF, et al. Practice guidelines for the management of community-acquired pneumonia in adults. Clin Infect Dis. 2000; 31:347-82. [IDIS 454042] [PubMed 10987697]

20. American Thoracic Society. Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med. 2001; 163:1730-54. [IDIS 466552] [PubMed 11401897]

21. Bartoloni A, Strohmeyer M, Corti G et al. Multicenter randomized trial comparing meropenem (1.5 g daily) and imipenem/cilastatin (2 g daily) in the hospital treatment of community-acquired pneumonia. Drugs Exp Clin Res. 1999; 25:243-52. [PubMed 10713862]

22. Alvarez Lerma F and the Serious Infection Study Group. Efficacy of meropenem as monotherapy in the treatment of ventilator-associated pneumonia. J Chemother. 2001; 13:70-81. [PubMed 11233804]

23. Mandell LA, Bartlett JG, Dowell SF et al. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis. 2003; 37:1405-33. [IDIS 516151] [PubMed 14614663]

24. Anon. Choice of antibacterial drugs. Med Lett Treat Guid. 2004; 2:18-26.

25. Committee on Infectious Diseases, American Academy of Pediatrics. Red book: 2003 report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003.

26. Anon. Drugs for pneumonia. Med Lett Treat Guid. 2003; 1:83-8.

27. American Thoracic Society and the Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005; 171:388-416. [PubMed 15699079]

28. Solomkin JS, Mazuski JE, Baron EJ et al. Guidelines for the selection of anti-infective agents for complicated intra-abdominal infections. Clin Infect Dis. 2003; 37:997-1005. [IDIS 511206] [PubMed 14523762]

29. Tunkel AR, Hartman BJ, Kaplan SL et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004; 39:1267-84. [IDIS 537717] [PubMed 15494903]

30. Yogev R, Guzman-Cottrill J. Bacterial meningitis in children. Critical review of current concepts. Drugs. 2005; 65:1097-112. [PubMed 15907145]

31. US Army Medical Research Institute of Infectious Disease. USAMRIID’s medical management of biologic casualties handbook. 5th ed. USAMRIID: Fort Detrick, MD; 2004 Aug:32-8,D2.

32. Cheng AC, Fisher DA, Anstey NM et al. Outcomes of patients with melioidosis treated with meropenem. Antimicrob Agents Chemother. 2004; 48:1763-5. [IDIS 514926] [PubMed 15105132]

33. Currie BJ. Melioidosis: an important cause of pneumonia in residents of and travelers returned from endemic regions. Eur Respir J. 2003; 22:542-50. [PubMed 14516149]

34. Bossi P, Tegnell A, Baka A et al. BICHAT guidelines for the clinical management of glanders and melioidosis and bioterrorism-related glanders and melioidosis. Euro Surveill. 2004; 9:1-6.

35. Nacarkucuk E, Saglam H, Okan M. Meropenem decreases serum level of valproic acid. Pediatr Neurol. 2004; 31:232-4. [PubMed 15351028]

36. Santucci M, Parmeggiani A, Riva R. Seizure worsening caused by decreased serum valproate during meropenem therapy. J Child Neurol. 2005; 20:456-7. [PubMed 15968935]

37. Coves-Orts FJ, Borras-Blasco J, Navarro-Ruiz A et al. Acute seizures due to a probable interaction between valproic acid and meropenem. Ann Pharmacother. 2005; 39:533-7. [PubMed 15701769]

38. Cox CE, Holloway WJ, Geckler RW. A multicenter comparative study of meropenem and imipenem/cilastatin in the treatment of complicated urinary tract infections in hospitalized patients. Clin Infect Dis. 1995; 21:86-92. [IDIS 351435] [PubMed 7578765]

39. Sejvar JJ, Tenover FC, Stephens DS. Management of anthrax meningitis. Lancet Infect Dis. 2005; 5:287-95. [PubMed 15854884]

40. Drago L, De Vecchi E, Lombardi A et al. Bactericidal activity of levofloxacin, gatifloxacin, penicillin, meropenem and rokitamycin against Bacillus anthracis clinical isolates. J Antimicrob Chemother. 2002; 50:1059-63. [PubMed 12461034]

41. Inglesby TV, O’Toole T, Henderson DA et al for the Working Group on Civilian Biodefense. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA. 2002; 287:2236-52. [IDIS 480001] [PubMed 11980524]

42. Centers for Disease Control and Prevention. Update: investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001. MMWR Morb Mortal Wkly Rep. 2001; 50:909-19. [IDIS 471910] [PubMed 11699843]

43. Zanetti G, Harbarth SJ, Trampuz A et al. Meropenem (1.5 g/day) is as effective as imipenem/cilastatin (2 g/day) for the treatment of moderately severe intra-abdominal infections. Int J Antimicrob Agents. 1999; 11:107-13. [PubMed 10221413]

44. Odio CM, Puig JR, Feris JM et al. Prospective, randomized, investigator-blinded study of the efficacy and safety of meropenem vs cefotaxime therapy in bacterial meningitis in children. Pediatr Infect Dis J. 1999; 18:581-90. [IDIS 431327] [PubMed 10440432]

45. Vandecasteele SJ, Verhaegen J, Colaert J et al. Failure of cefotaxime and meropenem to eradicate meningitis caused by an intermediately susceptible Streptococcus pneumoniae strain. Eur J Clin Microbiol Infect Dis. 2001; 20:751-2. [PubMed 11757981]

46. Schmutzhard E, Williams KJ, Vukmirovits G et al. A randomised comparison of meropenem with cefotaxime or ceftriaxone for the treatment of bacterial meningitis in adults. J Antimicrob Chemother. 1995; 36(suppl A):85-97. [IDIS 353282] [PubMed 8543502]

47. Chimata M, Nagase M, Suzuki Y et al. Pharmacokinetics of meropenem in patients with various degrees of renal function, including patients with end-stage renal disease. Antimicrob Agents Chemother. 1993; 37:229-33. [IDIS 309214] [PubMed 8452352]

48. Christensson BA, Nilsson-Ehle I, Hutchison M et al. Pharmacokinetics of meropenem in subjects with various degrees of renal impairment. Antimicrob Agents Chemother. 1992; 36:1532-7. [IDIS 298969] [PubMed 1510451]

49. Krueger WA, Schroeder TH, Hutchison M et al. Pharmacokinetics of meropenem in critically ill patients with acute renal failure treated by continuous hemodiafiltration. Antimicrob Agents Chemother. 1998; 42:2421-4. [IDIS 412436] [PubMed 9736574]

50. Thalhammer F, Horl WH. Pharmacokinetics of meropenem in patients with renal failure and patients receiving renal replacement therapy. Clin Pharmacokinet. 2000; 39:271-9. [PubMed 11069213]

51. Giles LJ, Jennings AC, Thomson AH et al. Pharmacokinetics of meropenem in intensive care unit patients receiving continuous veno-venous hemofiltration or hemodiafiltration. Crit Care Med. 2000; 28:632-7. [IDIS 443198] [PubMed 10752806]

52. Robatel C, Decosterd LA, Biollaz J. Pharmacokinetics and dosage adaptation of meropenem during continuous venovenous hemodiafiltration in critically ill patients. J Clin Pharmacol. 2003; 43:1329-40. [IDIS 508566] [PubMed 14615469]

53. Valtonen M, Tiula E, Backman JT et al. Elimination of meropenem during continuous veno-venous haemofiltration and haemodiafiltration in patients with acute renal failure. J Antimicrob Chemother. 2000; 45:701-4. [IDIS 447292] [PubMed 10797097]

54. Reviewers’ comments (personal observations).

55. Ziemba. Wilmington, DE: Personal communication.

56. Johnson S, Gerding DN. Clostridium difficile-associated diarrhea. Clin Infect Dis. 1998; 26:1027-36. [IDIS 407733] [PubMed 9597221]

57. Gerding DN, Johnson S, Peterson LR et al for the Society for Healthcare Epidemiology of America. Position paper on Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol. 1995; 16:459-77. [PubMed 7594392]

58. Fekety R for the American College of Gastroenterology Practice Parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. Am J Gastroenterol. 1997; 92:739-50. [IDIS 386628] [PubMed 9149180]

59. American Society of Health-System Pharmacists Commission on Therapeutics. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease. Am J Health-Syst Pharm. 1998; 55:1407-11. [IDIS 407213] [PubMed 9659970]

60. Goldstein SL, Murry DJ, Aleksic SM et al. Meropenem pharmacokinetics in children and adolescents receiving hemodialysis. Pediatr Nephrol. 2001; 16:1015-8. [PubMed 11793091]

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:743-9.

c. Anon. The choice of antibacterial drugs. Med Lett Drugs Ther. 2001; 43:69-78. [PubMed 11518876]

d. Committee on Infectious Diseases, American Academy of Pediatrics. 2000 Red book: report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2000:161-2,182-3,196-8,364-5,411-2.

Hide
(web4)