Pharmacologic Category
Dosing: Adult
Note: Infusion method: Dosing is presented based on the traditional infusion method over 30 minutes, unless otherwise specified.
Usual dosage range:
Traditional intermittent infusion method (over 30 minutes): IV: 500 mg every 6 hours or 1 to 2 g every 8 hours; 500 mg every 6 hours achieves comparable pharmacokinetic and pharmacodynamic parameters to 1 g every 8 hours (Kuti 2003; Lodise 2006).
Extended infusion method (off-label): IV: 1 to 2 g every 8 hours over 3 hours. May give a loading dose of 1 to 2 g over 30 minutes, especially when rapid attainment of therapeutic drug concentrations is desired (eg, sepsis) (Crandon 2011; SCCM [Rhodes 2017]).
Continuous infusion method (off-label): IV: 2 g every 8 hours over 8 hours or 3 g every 12 hours over 12 hours (Venugopalan 2018). May give a loading dose of 1 to 2 g over 30 minutes, especially when rapid attainment of therapeutic drug concentrations is desired (eg, sepsis) (SCCM [Rhodes 2017]).
Note: Extended and continuous infusion methods are based largely on pharmacokinetic and pharmacodynamic modeling data (Crandon 2011; Dulhunty 2015; Yu 2018). A prolonged infusion strategy has a greater likelihood of attaining pharmacokinetic/pharmacodynamic targets and may offer clinical benefit in patients with severe infections or less susceptible pathogens (Yu 2018). Meropenem stability (admixed with NS at a concentration of 20 mg/mL) at room temperature for >1 hour or under refrigeration for >15 hours is not supported by the manufacturer. Data exist supporting stability for extended and continuous infusion when admixed with NS at a concentration of 14.3 mg/mL at room temperature for ≤7 hours (Fawaz 2019) and at a concentration of 20 mg/mL under refrigeration for ≤24 hours (Patel 1997). Pharmacokinetic data support the use of an admixture of 10 mg/mL in NS as stable at room temperature for an infusion duration ≤12 hours (Venugopalan 2018).
Indication-specific dosing:
Anthrax (off-label use): Note: Consult public health officials for event-specific recommendations.
Systemic (meningitis excluded), treatment (alternative agent): IV: 2 g every 8 hours as part of an appropriate combination regimen for 2 weeks or until clinically stable, whichever is longer (CDC [Hendricks 2014]).
Meningitis, treatment: IV: 2 g every 8 hours as part of an appropriate combination regimen for 2 to 3 weeks or until clinically stable, whichever is longer (CDC [Hendricks 2014]).
Note: Antitoxin should also be administered. Following the course of IV combination therapy for systemic anthrax infection (including meningitis), patients exposed to aerosolized spores require oral monotherapy to complete a total antimicrobial course of 60 days (CDC [Hendricks 2014]).
Bite wound infection, treatment, animal or human bite (alternative agent) (off-label use): IV: 1 g every 8 hours; duration of treatment for established infection (which may include oral step-down therapy) is typically 5 to 14 days (Baddour 2019a; Baddour 2019b; IDSA [Stevens 2014]).
Bloodstream infection (gram-negative bacteremia) (off-label use): For empiric therapy of known or suspected gram-negative organisms (including Pseudomonas aeruginosa) or pathogen-directed therapy for organisms resistant to other agents.
IV: 1 g every 8 hours (IDSA [Mermel 2009]); for empiric therapy in patients with neutropenia, severe burns, sepsis, or septic shock, give as part of an appropriate combination regimen (Kanj 2019a; Moehring 2019a; SCCM [Rhodes 2017]). Note: For critical illness or infection with an organism with an elevated minimum inhibitory concentration (MIC), some experts prefer the extended or continuous infusion method and/or increasing the dose to 2 g every 8 hours (Del Bono 2017; Moehring 2019a; SCCM [Rhodes 2017]).
Duration of therapy: Usual duration is 7 to 14 days depending on the source, pathogen, extent of infection, and clinical response; a 7-day duration is recommended for patients with uncomplicated Enterobacteriaceae infection who respond appropriately to antibiotic therapy (Moehring 2019a; Yahav 2018). Note: If neutropenic, extend treatment until afebrile for 2 days and neutrophil recovery (ANC ≥500 cells/mm3 and increasing) (IDSA [Freifeld 2011]). For P. aeruginosa bacteremia in neutropenic patients, some experts treat for a minimum of 14 days and until recovery of neutrophils (Kanj 2019b).
Cystic fibrosis, acute pulmonary exacerbation (off-label use): For empiric or targeted therapy for P. aeruginosa or other gram-negative bacilli.
IV: 2 g every 8 hours, most often given as part of an appropriate combination regimen (Chmiel 2014; Flume 2009). Note: Some experts prefer the extended or continuous infusion method to optimize exposure (Delfino 2018; Kuti 2004; Simon 2019).
Duration of therapy: Duration is usually 10 days to 3 weeks or longer based on clinical response (Flume 2009; Simon 2019).
Diabetic foot infection, moderate to severe (off-label use): As a component of empiric therapy in patients at risk for P. aeruginosa (eg, significant water exposure, macerated wound) or other resistant gram-negative bacteria.
IV: 1 g every 8 hours. Duration (which may include oral step-down therapy) is usually 2 to 4 weeks in the absence of osteomyelitis (IDSA [Lipsky 2012]; Weintrob 2019).
Intra-abdominal infection, health care-associated or high-risk community-acquired infection: Note: For community-acquired infection, reserve for severe infection or patients at high risk of adverse outcome and/or resistance (Barshak 2019; IDSA [Solomkin 2010]). As a component of empiric therapy in patients at risk for P. aeruginosa or other resistant gram-negative bacteria.
Cholecystitis, acute: IV: 1 g every 8 hours; continue for 1 day after gallbladder removal or until clinical resolution in patients managed nonoperatively (Gomi 2018; SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]; Vollmer 2019).
Other intra-abdominal infection (eg, cholangitis, perforated appendix, diverticulitis, intra-abdominal abscess): IV: 1 g every 8 hours. Total duration of therapy (which may include oral step-down therapy) is 4 to 7 days following adequate source control (Gomi 2018; SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]); for infections managed without surgical or percutaneous intervention, a longer duration may be necessary (Barshak 2019; Pemberton 2019). Note: For patients who are critically ill or at high risk for infection with drug-resistant pathogens, some experts favor the extended or continuous infusion method (Barshak 2019; WSES [Sartelli 2017]).
Intracranial abscess (brain abscess, intracranial epidural abscess) and spinal epidural abscess (off-label use): As a component of empiric or directed therapy in patients at risk for P. aeruginosa or other resistant gram-negative bacteria (eg, neurosurgical or immunocompromised patients).
IV: 2 g every 8 hours as part of an appropriate combination regimen; duration generally ranges from 4 to 8 weeks for brain abscess and spinal epidural abscess and 6 to 8 weeks for intracranial epidural abscess (Bodilsen 2018; Sexton 2019a; Sexton 2019b; Southwick 2019).
Melioidosis (Burkholderia pseudomallei infection) (off-label use): Initial intensive therapy: IV: 1 g every 8 hours for 10 to 14 days; a longer duration may be necessary depending on disease severity and site of infection (Cheng 2004; Inglis 2006; Lipsitz 2012). Some experts recommend 2 g every 8 hours for patients with neurological involvement and adding sulfamethoxazole and trimethoprim for patients with focal disease of the CNS, prostate, bone, joint, skin, or soft tissue (Currie 2019). Note: Following the course of parenteral therapy, eradication therapy with oral antibiotics for ≥12 weeks is recommended (Lipsitz 2012).
Meningitis, bacterial: As a component of empiric therapy for health care-associated infections or infections in immunocompromised patients, or as pathogen-specific therapy for gram-negative bacteria resistant to other antibiotics (eg, P. aeruginosa, Acinetobacter spp.).
IV: 2 g every 8 hours. Treatment duration is 7 to 21 days depending on causative pathogen(s) and clinical response; 10 to 14 days is the minimum duration for gram-negative bacilli, although some experts prefer ≥21 days (Hasbun 2019; IDSA [Tunkel 2004]; IDSA [Tunkel 2017]). Note: Consider use of an extended or continuous infusion for more resistant pathogens (Capitano 2004; IDSA [Tunkel 2017]).
Neutropenic enterocolitis (typhlitis) (alternative agent) (off-label use): Note: Reserve for patients colonized or infected with a resistant gram-negative bacillus, such as an extended-spectrum beta-lactamase (ESBL)-producing organism (Wong Kee Song 2019).
IV: 1 g every 8 hours; continue until neutropenia is resolved and clinically improved, then switch to oral antibiotics. The total duration of antibiotics is generally 14 days following recovery from neutropenia (IDSA [Freifeld 2011]; Wong Kee Song 2019).
Neutropenic fever, high-risk cancer patients (empiric therapy) (off-label use): Note: High-risk patients are those expected to have an ANC ≤100 cells/mm3 for >7 days or an ANC ≤100 cells/mm3 for any expected duration if there are ongoing comorbidities (eg, sepsis, mucositis, significant hepatic or renal dysfunction) (IDSA [Freifeld 2011]); some experts use an ANC cutoff of <500 cells/mm3 to define high-risk patients (Wingard 2019).
IV: 1 g every 8 hours until afebrile for ≥48 hours and resolution of neutropenia (ANC ≥500 cells/mm3 and increasing) or standard duration for the specific infection identified, if longer than the duration of neutropenia. Additional agent(s) may be needed depending on clinical status (IDSA [Freifeld 2011]; Ohata 2011; Wingard 2019). Some experts prefer the extended or continuous infusion method, particularly in those who are critically ill (Fehér 2014; Moehring 2019b; SCCM [Rhodes 2017]; Wingard 2019).
Osteomyelitis and/or discitis (off-label use): IV: 1 g every 8 hours for ≥6 weeks (IDSA [Berbari 2015]; Osmon 2019). For empiric therapy, use in combination with other appropriate agents (IDSA [Berbari 2015]).
Pneumonia (off-label use):
Community-acquired pneumonia: For empiric therapy of inpatients at risk of infection with a multidrug-resistant, gram-negative pathogen(s), including P. aeruginosa:
IV: 1 g every 8 hours as part of an appropriate combination regimen. Total duration (which may include oral step-down therapy) is a minimum of 5 days; a longer course may be required for P. aeruginosa infection. Patients should be clinically stable with normal vital signs prior to discontinuation (ATS/IDSA [Metlay 2019]).
Hospital-acquired or ventilator-associated pneumonia: For empiric therapy or pathogen-specific therapy for multidrug-resistant gram-negative pathogen(s) (eg, P. aeruginosa, Acinetobacter spp.):
IV: 1 g every 8 hours, as part of an appropriate combination regimen. Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (IDSA/ATS [Kalil 2016]), but a longer course may be required for severe or complicated infection or for P. aeruginosa infection (Kanj 2019c). Note: Some experts reserve meropenem for patients at risk of infection with a multidrug-resistant (MDR) gram-negative pathogen(s), including P. aeruginosa (Klompas 2019). Some experts prefer the extended or continuous infusion method, particularly in those who are critically ill (Klompas 2019; Moehring 2019b; SCCM [Rhodes 2017]).
Prosthetic joint infection (pathogen-directed therapy for multidrug-resistant gram-negative bacilli, including P. aeruginosa) (off-label use): IV: 1 g every 8 hours; duration varies, but is generally 4 to 6 weeks for patients who undergo resection arthroplasty (IDSA [Osmon 2013]).
Sepsis and septic shock (broad-spectrum empiric therapy, including P. aeruginosa) (off-label use): IV: 1 to 2 g every 8 hours in combination with other appropriate agent(s) (Jaruratanasirikul 2015; Moehring 2019a; Schmidt 2019; Sjövall 2018). Initiate therapy as soon as possible once there is recognition of sepsis or septic shock. Usual duration of treatment is dependent on underlying source but is typically 7 to 10 days or longer depending upon clinical response. Consider discontinuation if a noninfectious etiology is identified (SCCM [Rhodes 2017]; Schmidt 2019). Note: Some experts prefer the extended or continuous infusion method (Moehring 2019b; SCCM [Rhodes 2017]; Sjövall 2018).
Skin and soft tissue infection (moderate to severe infection, necrotizing infection, select surgical site infections [intestinal, GU tract]), broad-spectrum empiric coverage, including P. aeruginosa: IV: 1 g every 8 hours as part of an appropriate combination regimen. Usual duration is 10 to 14 days based on clinical response; for necrotizing infection, continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for ≥48 hours (Fish 2006; IDSA [Stevens 2014]; Kanj 2019d).
Urinary tract infection, complicated (including pyelonephritis) (off-label use): IV: 1 g every 8 hours; when used for empiric therapy, use alone or in combination with other appropriate agents. Switch to an appropriate oral regimen once patient has improvement in symptoms, if culture and susceptibility results allow. Duration of therapy depends on the antimicrobial chosen to complete the regimen and ranges from 5 to 14 days. Note: Reserve for critically ill patients or for patients with risk factor(s) for MDR pathogens, including ESBL-producing organisms and P. aeruginosa (Hooton 2019).
* See Dosage and Administration in AHFS Essentials for additional information.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Renal Impairment: Adult
Manufacturer’s labeling:
CrCl >50 mL/minute: No dosage adjustment necessary.
CrCl 26 to 50 mL/minute: Administer recommended dose based on indication every 12 hours
CrCl 10 to 25 mL/minute: Administer one-half recommended dose based on indication every 12 hours
CrCl <10 mL/minute: Administer one-half recommended dose based on indication every 24 hours
Alternative recommendations: Note: Renally adjusted dose recommendations are based on doses of 1 to 2 g every 8 hours.
GFR 10 to 50 mL/minute: Administer recommended dose based on indication every 12 hours (Aronoff 2007)
GFR <10 mL/minute: Administer recommended dose based on indication every 24 hours (Aronoff 2007)
Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): Meropenem and its metabolite are readily dialyzable: 500 mg every 24 hours (Heintz 2009). Note: Dosing dependent on the assumption of 3-times-weekly, complete IHD sessions.
Peritoneal dialysis (off-label dose): Administer recommended dose (based on indication) every 24 hours (Aronoff 2007).
Continuous renal replacement therapy (CRRT) (Heintz 2009; Kuti 2005; Trotman 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment:
CVVH: Consider loading dose of 1 g followed by either 500 mg every 8 hours or 1 g every 8 to 12 hours
CVVHD/CVVHDF: Consider loading dose of 1 g followed by either 500 mg every 6 to 8 hours or 1 g every 8 to 12 hours
Note: Consider giving patients receiving CVVHDF dosages of 750 mg every 8 hours or 1.5 g every 12 hours (Heintz 2009). Substantial variability exists in various published recommendations, ranging from 1 to 3 g daily in 2 to 3 divided doses. One gram every 12 hours achieves a target trough of ~4 mg/L.
Dosing: Hepatic Impairment: Adult
No dosage adjustment necessary.
Dosing: Pediatric
General dosing, susceptible infection (non-CNS): Infants, Children, and Adolescents: IV: 20 mg/kg/dose every 8 hours; maximum dose: 1,000 mg/dose (Bradley 2017)
Cystic fibrosis, pulmonary exacerbation: Limited data available: Infants, Children, and Adolescents: IV: 40 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose (Zobell 2012)
Febrile neutropenia, empiric treatment: Limited data available: Infants, Children, and Adolescents: IV: 20 mg/kg/dose every 8 hours; maximum dose: 1,000 mg/dose (Bradley 2017; Lehrnbecher 2017)
Intra-abdominal infection, complicated: Note: IDSA guidelines recommend treatment duration of 4 to 7 days (Solomkin 2010)
Infants 1 to <3 months:
GA <32 weeks: IV: 20 mg/kg/dose every 8 hours
GA ≥32 weeks: IV: 30 mg/kg/dose every 8 hours
Infants ≥3 months, Children, and Adolescents: IV: 20 mg/kg/dose every 8 hours; maximum dose: 1,000 mg/dose
Meningitis: Infants (Limited data available <3 months of age), Children, and Adolescents: IV: 40 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose (Bradley 2017); duration of therapy dependent upon pathogen: N. meningitidis, H. influenza: 7 days; S. pneumoniae: 10 to 14 days; aerobic gram-negative bacilli: 21 days (Tunkel 2004)
Skin and skin structure infection, complicated:
Manufacturer's labeling: Infants ≥3 months, Children, and Adolescents: IV: 10 mg/kg/dose every 8 hours; maximum dose: 500 mg/dose
Severe or necrotizing infections: Infants, Children, and Adolescents: IV: 20 mg/kg/dose every 8 hours; maximum dose: 1,000 mg/dose (IDSA [Stevens 2014])
Dosing: Renal Impairment: Pediatric
Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling. Some clinicians have used the following (Aronoff 2007): Note: Renally adjusted dose recommendations are based on doses of 20 to 40 mg/kg/dose every 8 hours:
GFR >50 mL/minute/1.73 m2: No adjustment required.
GFR 30 to 50 mL/minute/1.73 m2: Administer 20 to 40 mg/kg/dose every 12 hours
GFR 10 to 29 mL/minute/1.73 m2: Administer 10 to 20 mg/kg/dose every 12 hours
GFR <10 mL/minute/1.73 m2: Administer 10 to 20 mg/kg/dose every 24 hours
Intermittent hemodialysis (IHD): Meropenem and metabolite are readily dialyzable: 10 to 20 mg/kg/dose every 24 hours; on dialysis days give dose after hemodialysis
Peritoneal dialysis (PD): 10 to 20 mg/kg/dose every 24 hours
Continuous renal replacement therapy (CRRT): 20 to 40 mg/kg/dose every 12 hours
Dosing: Hepatic Impairment: Pediatric
No dosage adjustment necessary.
Calculations
Use: Labeled Indications
Intra-abdominal infections: Treatment of complicated appendicitis and peritonitis in adult and pediatric patients caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, Bacteroides thetaiotaomicron, and Peptostreptococcus species.
Meningitis, bacterial: Treatment of bacterial meningitis in pediatric patients 3 months and older caused by Haemophilus influenzae, Neisseria meningitidis, and penicillin-susceptible isolates of Streptococcus pneumoniae.
Skin and skin structure infection, complicated: Treatment of complicated skin and skin structure infections in adults and pediatric patients 3 months and older caused by Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), P. aeruginosa, E. coli, Proteus mirabilis, B. fragilis, and Peptostreptococcus species.
* See Uses in AHFS Essentials for additional information.
Use: Off-Label: Adult
AnthraxLevel of Evidence [G]
Based on the Centers for Disease Control and Prevention (CDC) expert panel meetings on prevention and treatment of anthrax, meropenem is an effective and recommended agent for the treatment of anthrax meningitis and an effective and recommended alternative agent for systemic anthrax.
Bite wound infection, treatment, animal or human biteLevel of Evidence [G]
Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTIs), meropenem is an effective and recommended alternative agent for treatment of animal or human bite wounds.
Bloodstream infection (gram-negative bacteremia)Level of Evidence [C, G]
Based on the IDSA guidelines for the diagnosis and management of intravascular catheter-related infection, meropenem is effective and recommended in the management of catheter-related bloodstream infection.
Clinical experience also suggests the utility of meropenem for the treatment of bloodstream infection caused by gram-negative pathogens, including Pseudomonas aeruginosa Ref.
Cystic fibrosis, acute pulmonary exacerbationLevel of Evidence [B]
Data from several randomized trials of patients with cystic fibrosis and infection with P. aeruginosa treated with meropenem (with and without the use of tobramycin) support the use of meropenem in the treatment of this condition Ref. Clinical experience also suggests the utility of meropenem for pulmonary exacerbation in patients with cystic fibrosis Ref.
Diabetic foot infection, moderate to severeLevel of Evidence [C]
Clinical experience suggests the utility of meropenem for the treatment of moderate to severe diabetic foot infection in patients at risk for P. aeruginosa Ref.
Intracranial abscess (brain abscess, intracranial epidural abscess) and spinal epidural abscessLevel of Evidence [C]
Data from a retrospective study suggest that meropenem may be beneficial for the treatment of brain abscess Ref. Clinical experience suggests the utility of meropenem for the treatment of brain abscess, intracranial epidural abscess, and spinal epidural abscess caused by gram-negative pathogens, including P. aeruginosa Ref.
Melioidosis (Burkholderia pseudomallei infection)Level of Evidence [C]
Melioidosis is a worldwide subtropical and tropical bacterial disease caused by contact with Burkholderia pseudomallei-contaminated water or soil Ref. Data from a limited number of patients treated with meropenem (case series of 63 patients in a single institution) suggest that meropenem may be beneficial for the treatment of this condition Ref.
A US Department of Health and Human Services workshop on treatment of and postexposure prophylaxis for B. pseudomallei and Burkholderia mallei infection also supports the use of meropenem as a second-line agent for initial treatment of melioidosis Ref.
Neutropenic enterocolitis (typhlitis)Level of Evidence [C, G]
Based on the IDSA clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update, meropenem is effective and recommended in the management of neutropenic enterocolitis.
Clinical experience also suggests the utility of meropenem as an alternative agent for the treatment of neutropenic enterocolitis Ref.
Neutropenic fever, high-risk cancer patientsLevel of Evidence [G]
Based on the IDSA clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update, meropenem is effective and recommended in the management of febrile neutropenia.
Osteomyelitis and/or discitisLevel of Evidence [C, G]
Clinical experience suggests that meropenem may be beneficial for the treatment of osteomyelitis Ref.
Based on the IDSA guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults, meropenem is an effective and recommended agent for the treatment of native vertebral osteomyelitis due to P. aeruginosa or Enterobacteriaceae.
PneumoniaLevel of Evidence [G]
Based on the American Thoracic Society and IDSA guidelines on the diagnosis and treatment of adults with community-acquired pneumonia, meropenem, as part of an appropriate combination regimen, is an effective and recommended treatment option for patients with community-acquired pneumonia at risk for P. aeruginosa infection.
Based on the IDSA and ATS guidelines on the management of adults with hospital-acquired and ventilator-associated pneumonia, meropenem alone or in combination with other antimicrobials (dependent on patient factors), is an effective and recommended option for empiric treatment of hospital-acquired or ventilator-associated pneumonia.
Prosthetic joint infection (pathogen-directed therapy for multidrug-resistant gram-negative bacilli, including P. aeruginosa)Level of Evidence [G]
Based on the IDSA guidelines on the diagnosis and management of prosthetic joint infection, meropenem is effective and recommended in the management of prosthetic joint infection.
Sepsis and septic shock (broad-spectrum empiric therapy, including P. aeruginosa)Level of Evidence [C]
Clinical experience suggests the utility of meropenem for the treatment of sepsis or septic shock caused by an infectious etiology Ref.
Urinary tract infection, complicated (including pyelonephritis)Level of Evidence [B]
Data from a multicenter, randomized, parallel-group study support the use of meropenem in the treatment of complicated urinary tract infections Ref. Clinical experience also suggests the utility of meropenem in the treatment of complicated urinary tract infections, although use should be reserved for critically ill patients or patients with risk factor(s) for multidrug-resistant pathogens, including extended-spectrum beta-lactamase-producing organisms Ref.
Level of Evidence Definitions
Level of Evidence Scale
Class and Related Monographs
Clinical Practice Guidelines
Catheter-related Blood Stream Infections:
IDSA, “Diagnosis and Management of Intravascular Catheter-Related Infection,” July 2009
Cystic Fibrosis:
Cystic Fibrosis Foundation, “Cystic Fibrosis Pulmonary Guidelines: Treatment of Pulmonary Exacerbations,” 2009
Diabetic Foot Infection:
Infectious Diseases Society of America (IDSA), “The Diagnosis and Treatment of Diabetic Foot Infections,” 2012
Infective Endocarditis:
British Society for Antimicrobial Chemotherapy (BSAC), "Guidelines for the Diagnosis and Antibiotic Treatment of Endocarditis in Adults," 2012
Intra-abdominal Infection:
Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada), “Canadian Practice Guidelines for Surgical Intra-Abdominal Infections,” Spring 2010
Infectious Diseases Society of America (IDSA), “Diagnosis and Management of Complicated Intra-Abdominal Infections in Adults and Children,” January 2010
Meningitis, Bacterial:
IDSA, “Practice Guidelines for the Management of Bacterial Meningitis,” November 2004
Meningitis and Ventriculitis, Health Care Associated:
IDSA, "Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis," February 2017.
Neutropenic Fever:
ASCO/IDSA, "Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy," February 2018
International Pediatric Fever and Neutropenia Guideline Panel (Lehrnbecher et al), “Guideline for the Management of Fever and Neutropenia in Children With Cancer and/or Undergoing Hematopoietic Stem-Cell Transplantation,” December, 2012
Opportunistic Infections:
DHHS, Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, October 2014 [Note: Information contained within this monograph is pending revision based on these more recent guidelines]
Osteomyelitis, Native Vertebral:
IDSA, "Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults," 2015
Pneumonia, Community Acquired:
ATS/IDSA, "Diagnosis and Treatment of Adults With Community-Acquired Pneumonia," October 2019
Pneumonia, Hospital Acquired and Ventilator Associated:
IDSA/ATS, "Management of Adults with Hospital-Acquired and Ventilator-Associated Pneumonia," July 2016.
Prosthetic Joint Infection:
IDSA, “Diagnosis and Management of Prosthetic Joint Infection: Clinical Practice Guideline,” January 2013
Skin and Soft-tissue Infection:
IDSA, “Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections,” June 2014.
Urinary Tract Infection:
IDSA, “International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases,” March 2011
Administration: IV
Administer IV infusion over 15 to 30 minutes; IV bolus injection (5 to 20 mL) over 3 to 5 minutes
Extended infusion administration (off-label method): Administer over 3 hours (Crandon 2011; Dandekar 2003). Note: Must consider meropenem's limited room temperature stability if using extended infusions.
Continuous infusion method (off-label method): IV: Administer every 8 hours over 8 hours or every 12 hours over 12 hours (Venugopalan 2018). Note: Must consider meropenem's limited room temperature stability if using extended infusions.
Administration: Injectable Detail
pH: 7.3 to 8.3
Administration: Pediatric
Parenteral:
IV push: Infants ≥3 months, Children, and Adolescents: Administer reconstituted solution (up to 1 g) over 3 to 5 minutes; safety data is limited with 40 mg/kg doses up to a maximum of 2 g
Intermittent IV infusion: Further dilute reconstituted solution prior to administration
Infants <3 months: Administer as an IV infusion over 30 minutes
Infants ≥3 months, Children, and Adolescents: Administer IV infusion over 15 to 30 minutes
Note: Some studies have demonstrated enhanced pharmacodynamic effects when extending intermittent infusions to 4 hours (van den Anker 2009)
Dietary Considerations
Some products may contain sodium.
Storage/Stability
Freshly prepared solutions should be used. However, constituted solutions maintain satisfactory potency under the conditions described below. Solutions should not be frozen.
Store intact vials and unactivated Duplex containers at 20°C to 25°C (68°F to 77°F). Unactivated duplex units with foil strip removed from the drug chamber must be protected from light and used within 7 days at room temperature. Once activated, must be used within 1 hour if stored at room temperature or within 15 hours if stored under refrigeration. Do not freeze.
Dry powder should be stored at controlled room temperature 20°C to 25°C (68°F to 77°F).
Injection reconstitution: Stability in vial when constituted (up to 50 mg/mL) with:
SWFI: Stable for up to 3 hours at up to 25°C (77°F) or for up to 13 hours at up to 5°C (41°F).
Infusion admixture (1 to 20 mg/mL): Solution is stable when diluted in NS for 1 hour at up to 25°C (77°F) or 15 hours at up to 5°C (41°F). Solutions constituted with dextrose injection 5% should be used immediately. Note: Meropenem stability (admixed with NS at a concentration of 20 mg/mL) at room temperature for >1 hour or under refrigeration for >15 hours is not supported by the manufacturer. Data exist supporting stability for extended and continuous infusion when admixed with NS at a concentration of 14.3 mg/mL at room temperature for ≤7 hours (Fawaz 2019) and at a concentration of 20 mg/mL under refrigeration for ≤24 hours (Patel 1997). Pharmacokinetic data support the use of an admixture of 10 mg/mL in NS as stable at room temperature for an infusion duration ≤12 hours (Venugopalan 2018).
Duplex container: Following reconstitution/activation, use within 1 hour if stored at room temperature or 15 hours refrigerated
Preparation for Administration: Adult
Meropenem infusion vials may be reconstituted with SWFI. The 500 mg vials should be reconstituted with 10 mL, and 1 g vials with 20 mL. May be further diluted to a final concentration ranging from 1 to 20 mg/mL with a compatible solution for infusion. Consult detailed reference/product labeling for compatibility.
Duplex: Unlatch side tab, unfold, remove foil strip from drug chamber. Point set port in downward direction, fold container just below the diluent meniscus, and squeeze the diluent chamber until the seal between the diluent and drug powder opens. Agitate until dissolved.
Preparation for Administration: Pediatric
Parenteral: Reconstitute meropenem 500 mg and 1 g vials with 10 mL and 20 mL SWFI respectively to yield a concentration of 50 mg/mL. For IV infusion, may further dilute with D5W or NS to a final concentration ranging from 1 to 20 mg/mL.
Compatibility
See Trissel’s IV Compatibility Database
Open Trissel's IV Compatibility
Medication Patient Education with HCAHPS Considerations
What is this drug used for?
• It is used to treat bacterial infections.
Frequently reported side effects of this drug
• Headache
• Nausea
• Vomiting
• Diarrhea
• Constipation
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
• Seizures
• Stiff muscles
• Tremors
• Abnormal movements
• Burning or numbness feeling
• Severe loss of strength and energy
• Confusion
• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.
• Clostridium difficile (C. diff)-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools.
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
Medication Safety Issues
Sound-alike/look-alike issues:
Contraindications
Hypersensitivity to meropenem, other drugs in the same class, or any component of the formulation; patients who have experienced anaphylactic reactions to beta-lactams
Warnings/Precautions
Concerns related to adverse effects:
• Anaphylaxis/hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylaxis, have been reported (some without a history of previous allergic reactions to beta-lactams).
• CNS effects: Carbapenems have been associated with CNS adverse effects, including confusional states and seizures (myoclonic); use caution with CNS disorders (eg, brain lesions and history of seizures) and adjust dose in renal impairment to avoid drug accumulation, which may increase seizure risk. Outpatient use may result in paresthesias, seizures, delirium and/or headaches that can impair neuromotor function and alertness; patients should not operate machinery or drive until it is established that meropenem is well tolerated.
• Dermatological effects: Severe cutaneous adverse reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, erythema multiforme, and acute generalized exanthematous pustulosis have occurred; discontinue immediately for severe reactions.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required in patients with creatinine clearance ≤50 mL/minute. Increased seizure risk and thrombocytopenia have been reported in patients with renal impairment.
Concurrent drug therapy issues:
• Drug-drug interactions. Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
• Elderly: Lower doses (based upon renal function) are often required in the elderly.
* See Cautions in AHFS Essentials for additional information.
Geriatric Considerations
Adjust dose based on renal function.
Pregnancy Considerations
Incomplete transplacental transfer of meropenem was found using an ex vivo human perfusion model (Hnat 2005).
Information related to the use of meropenem in pregnancy is limited (Yoshida 2013).
Breast-Feeding Considerations
Meropenem is present in breast milk (Sauberan 2012).
Information related to the use of meropenem in breastfeeding women is limited. Based on information from one case report, the relative infant dose (RID) of meropenem is 0.18% compared to a weight-adjusted maternal dose of 3 g/day (Sauberan 2012).
In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).
The RID of meropenem was calculated by the authors of the case report using a milk concentration of 0.48 mcg/mL and the mothers actual weight, providing an estimated daily infant dose via breast milk of 0.097 mg/kg/day. This milk concentration was obtained following maternal administration meropenem 1 g IV every 8 hours beginning postpartum day 6. Adverse events were not observed in the breastfed infant (Sauberan 2012).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. In general, antibiotics that are present in breast milk may cause nondose-related modification of bowel flora. Monitor infants for GI disturbances, such as thrush or diarrhea (WHO 2002).
Lexicomp Pregnancy & Lactation, In-Depth
Briggs' Drugs in Pregnancy & Lactation
Adverse Reactions
1% to 10%:
Cardiovascular: Peripheral vascular disease (>1%), shock (1%), bradycardia (≤1%), cardiac arrest (≤1%), cardiac failure (≤1%), chest pain (≤1%), hypertension (≤1%), hypotension (≤1%), myocardial infarction (≤1%), peripheral edema (≤1%), pulmonary embolism (≤1%), syncope (≤1%), tachycardia (≤1%)
Central nervous system: Headache (2% to 8%), pain (≤5%), agitation (≤1%), anxiety (≤1%), chills (≤1%), confusion (≤1%), delirium (≤1%), depression (≤1%), dizziness (≤1%), drowsiness (≤1%), hallucination (≤1%), insomnia (≤1%), nervousness (≤1%), paresthesia (≤1%), seizure (≤1%)
Dermatologic: Skin rash (2% to 3%, includes diaper-area moniliasis in infants), pruritus (1%), dermal ulcer (≤1%), diaphoresis (≤1%), urticaria (≤1%)
Endocrine & metabolic: Hypoglycemia (>1%), hypervolemia (≤1%)
Gastrointestinal: Nausea (≤8%), diarrhea (4% to 7%), constipation (1% to 7%), vomiting (≤4%), oral candidiasis (≤2%), gastrointestinal disease (>1%), glossitis (1%), abdominal pain (≤1%), anorexia (≤1%), dyspepsia (≤1%), enlargement of abdomen (≤1%), flatulence (≤1%), intestinal obstruction (≤1%)
Genitourinary: Dysuria (≤1%), pelvic pain (≤1%), urinary incontinence (≤1%), vulvovaginal candidiasis (≤1%)
Hematologic & oncologic: Anemia (≤6%), hypochromic anemia (≤1%)
Hepatic: Cholestatic jaundice (≤1%), hepatic failure (≤1%), jaundice (≤1%)
Infection: Sepsis (2%)
Local: Inflammation at injection site (2%)
Neuromuscular & skeletal: Asthenia (≤1%), back pain (≤1%)
Renal: Renal failure (≤1%)
Respiratory: Pharyngitis (>1%), pneumonia (>1%), apnea (1%), asthma (≤1%), cough (≤1%), dyspnea (≤1%), hypoxia (≤1%), pleural effusion (≤1%), pulmonary edema (≤1%), respiratory tract disease (≤1%)
Miscellaneous: Accidental injury (>1%), fever (≤1%)
Frequency not defined:
Endocrine & metabolic: Hypokalemia, increased lactate dehydrogenase
Genitourinary: Hematuria
Hematologic & oncologic: Decreased hematocrit, decreased hemoglobin, decreased partial thromboplastin time, decreased prothrombin time, decreased white blood cell count, eosinophilia, leukocytosis, quantitative disorders of platelets
Hepatic: Increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, increased serum bilirubin
Renal: Increased blood urea nitrogen, increased serum creatinine
<1%, postmarketing, and/or case reports: Acute generalized exanthematous pustulosis, agranulocytosis, angioedema, Clostridioides (formerly Clostridium) difficile-associated diarrhea, DRESS syndrome, edema at insertion site, epistaxis, erythema multiforme, gastrointestinal hemorrhage, hemolytic anemia, hemoperitoneum, injection site reaction, leukopenia, localized phlebitis, local thrombophlebitis, melena, neutropenia, pain at injection site, positive direct Coombs test, positive indirect Coombs test, Stevens-Johnson syndrome, toxic epidermal necrolysis
* See Cautions in AHFS Essentials for additional information.
Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects
None known.
Drug Interactions Open Interactions
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Meropenem. Risk X: Avoid combination
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Risk D: Consider therapy modification
Valproate Products: Carbapenems may decrease the serum concentration of Valproate Products. Management: Concurrent use of carbapenem antibiotics with valproic acid is generally not recommended. Alternative antimicrobial agents should be considered, but if a concurrent carbapenem is necessary, consider additional anti-seizure medication. Risk D: Consider therapy modification
Test Interactions
Positive Coombs' [direct]
Monitoring Parameters
Perform culture and sensitivity testing prior to initiating therapy. Monitor for signs of anaphylaxis during first dose. During prolonged therapy, monitor renal function, liver function, CBC.
Advanced Practitioners Physical Assessment/Monitoring
Obtain renal function tests (dosage adjustment may be needed), liver function tests, and CBC with prolonged use. Assess results of culture and sensitivity tests and patient's allergy history prior to beginning treatment. Assess for signs of anaphylaxis with first dose. Assess for effectiveness of treatment. Test for C. difficile if patient develops diarrhea.
Nursing Physical Assessment/Monitoring
Check ordered labs and report any abnormalities. Monitor anaphylaxis with first dose. Educate patient on importance of adequate hydration. Monitor for severe or bloody diarrhea and send a specimen to the lab for C. difficile. Monitor for improvement with infection.
Dosage Forms: US
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Intravenous:
Merrem: 500 mg (1 ea [DSC]); 1 g (1 ea [DSC])
Generic: 500 mg (1 ea [DSC]); 1 g (1 ea [DSC])
Solution Reconstituted, Intravenous [preservative free]:
Merrem: 500 mg (1 ea); 1 g (1 ea) [pyrogen free]
Generic: 500 mg (1 ea); 1 g (1 ea); 1 g/50 mL in NaCl 0.9% (1 ea); 500 mg/50 mL in NaCl 0.9% (1 ea)
Dosage Forms: Canada
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Intravenous:
Merrem: 500 mg ([DSC]); 1 g ([DSC])
Generic: 500 mg (1 ea); 1 g (1 ea)
Anatomic Therapeutic Chemical (ATC) Classification
Generic Available (US)
Yes
Pricing: US
Solution (reconstituted) (Meropenem Intravenous)
1 g (per each): $13.20 - $52.00
500 mg (per each): $7.20 - $26.00
Solution (reconstituted) (Meropenem-Sodium Chloride Intravenous)
1 gm/50 mL (per each): $26.93
500 mg/50 mL (per each): $20.02
Solution (reconstituted) (Merrem Intravenous)
1 g (per each): $34.97
500 mg (per each): $17.40
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Mechanism of Action
Inhibits bacterial cell wall synthesis by binding to several of the penicillin-binding proteins, which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis; bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested
Pharmacodynamics/Kinetics
Distribution: Penetrates into most tissues and body fluids including urinary tract, peritoneal fluid, bone, bile, lung, bronchial mucosa, muscle tissue, heart valves (Craig 1997), and CSF (CSF penetration: Neonates and Infants ≤3 months: 70%)
Vd:
Neonates and Infants ≤3 months: Median: ~0.47 L/kg (Smith 2011)
Children: 0.3 to 0.4 L/kg (Blumer 1995)
Adults: 15 to 20 L
Protein binding: ~2%
Metabolism: Hepatic; hydrolysis of beta-lactam bond to open beta-lactam form (inactive) (Craig 1997)
Half-life elimination:
Neonates and Infants ≤3 months: Median: 2.7 hours; range: 1.6 to 3.8 hours (Smith 2011)
Infants and Children 3 months to 2 years: 1.5 hours
Children 2 to 12 years and Adults: 1 hour
Time to peak: Tissue: ~1 hour following infusion except in bile, lung, and muscle; CSF: 2 to 3 hours with inflamed meninges
Excretion: Urine (~70% as unchanged drug; ~28% inactive metabolite); feces (2%)
Clearance:
Neonates and Infants ≤3 months: 0.12 L/hour/kg (Smith 2011)
Infants and Children: 0.26 to 0.37 L/hour/kg (Blumer 1995)
Pharmacodynamics/Kinetics: Additional Considerations
Renal function impairment: Clearance correlates with creatinine clearance (CrCl) in patients with renal impairment.
Geriatric: Reduction in plasma clearance correlates with age-associated reduction in CrCl (Craig 1997)
Local Anesthetic/Vasoconstrictor Precautions
No information available to require special precautions
Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Infrequent occurrence of oral Candida infection and glossitis.
Effects on Bleeding
Hematologic disorder including decreased prothrombin time, decreased hematocrit, and platelet disorder.
Related Information
FDA Approval Date
June 21, 1996
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Brand Names: International
Accurem (TH); Archifar (HR, MT, SG); Aris (UA); Bestinem (ZW); Bironem (VN); Elpenem (LK); Enem (TH); Grambiot (PY); Haizheng Meite (CN); Lanmer (ID); Mabapenem (KR); Madiba (EC); Mapenem (TH); Mecapem (KR); Meflupin (TW); Melopen (TW); Menem IV (PH); Mepem (CN, TW); Mepenam (UA); Mero (TH); Merobac I.V. (CO); Merofen (ID); Merogram (TZ); Meromax (PH); Meronem (AE, BD, BE, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CL, CO, CR, CU, CY, CZ, DE, DK, DO, EE, EG, ES, ET, FI, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, HU, IE, IL, IN, IS, JM, JO, KE, LB, LR, LT, LU, MA, ML, MR, MT, MU, MW, MY, NE, NG, NI, NL, NO, PA, PE, PH, PK, PL, PR, PT, QA, RO, RU, SA, SC, SD, SE, SG, SI, SK, SL, SN, SR, SV, TH, TN, TR, TT, TZ, UG, UY, VE, VN, ZA, ZM, ZW); Meronia (TZ); Merop (PH); Meropemed (PE); Meropen (JP, KR, LK, PH); Meropevex (PH); Meroponia (IE); Merosan (ID); Merostarkyl (EG); Merovex (PH); Meroxi (ID); Merozan (PH); Merozen (PY); Merrem (BB, IT, MX, NZ); Mirage (EG); Monan (ZW); Monem (LK, MY, TH); Myron (TW); Newropenem (KR); Opimer (ID); Optinem (AT); Penem (ID); Penembact (NZ); Penomer (LK); Pisapem (EC); Pospenem (KR); Propenem (ID); Romenem (TH); Ronem (ID, UA, ZW); Ropen (PH); Tripenem (ID, MY); Zaxter (TH); Zeropenem (AR)
Last Updated 2/26/20