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Meropenem: Drug information

Meropenem: Drug information
(For additional information see "Meropenem: Patient drug information" and see "Meropenem: Pediatric drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)
Brand Names: US
  • Merrem [DSC]
Brand Names: Canada
  • Merrem [DSC];
  • TARO-Meropenem
Pharmacologic Category
  • Antibiotic, Carbapenem
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]).

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 gram-negative bacteria resistant to other agents (IDSA [Lipsky 2012]).

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 2020).

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 2021; SIS/IDSA [Solomkin 2010]).

Cholecystitis, acute uncomplicated: 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 2021).

Other intra-abdominal infection (eg, cholangitis, complicated cholecystitis, perforated appendix, diverticulitis, intra-abdominal abscess): IV: 1 g every 8 hours. Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Gomi 2018; Sawyer 2015; SIS [Mazuski 2017]); for diverticulitis or uncomplicated appendicitis managed without intervention, duration is 7 to 10 days (Barshak 2021; Pemberton 2021). 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 2021; 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 2021; 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 2020).

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 2020).

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 2020).

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 2020). Some experts prefer the extended or continuous infusion method, particularly in those who are critically ill (Fehér 2014; Moehring 2019b; SCCM [Rhodes 2017]; Wingard 2020).

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 patients with an immunocompromising condition, severe or complicated infection, or for P. aeruginosa infection. Patients should be clinically stable with normal vital signs prior to discontinuation (ATS/IDSA [Metlay 2019]; Ramirez 2020).

Hospital-acquired or ventilator-associated pneumonia: For empiric therapy (often as part of an appropriate combination regimen) or pathogen-specific therapy for multidrug-resistant gram-negative pathogen(s) (eg, P. aeruginosa, Acinetobacter spp.):

IV: 1 g every 8 hours. Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (IDSA/ATS [Kalil 2016]). Note: Some experts prefer extended or continuous infusion for critical illness or when treating a susceptible organism with an elevated minimum inhibitory concentration (Klompas 2021; 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 2021).

Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms) (off-label use):

Note: Reserve for critically ill patients or for patients with risk factor(s) for MDR pathogens, including ESBL-producing organisms and P. aeruginosa (Hooton 2021; IDSA [Tamma 2020]).

IV: 1 g every 8 hours. Switch to an appropriate oral regimen once symptoms improve, if culture and susceptibility results allow. Total duration of therapy ranges from 5 to 14 days and depends on clinical response and the antimicrobial chosen to complete the regimen (Hooton 2021; IDSA [Tamma 2020]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: IV:

Meropenem Dose Adjustments in Kidney Impairmenta,b

CrCl (mL/minute)

If the usual recommended dose is 1 g every 8 hoursc

If the usual recommended dose is 2 g every 8 hoursc

aChoose usual recommended dose based on indication and disease severity (see "Dosing: Adult"), then choose the adjusted dose from that column based on the patient's estimated CrCl.

bExpert opinion derived from manufacturer's labeling, Burger 2018, and Golightly 2013.

cDose may be administered using the traditional intermittent infusion method (over 30 minutes) or extended infusion method (over 3 hours). Extending the infusion time to 3 hours increases the likelihood of pharmacodynamic target attainment, especially in severe infections or those caused by pathogens with an elevated minimum inhibitory concentration. May give the first dose over 30 minutes when rapid achievement of pharmacodynamic targets is desired (Ahmed 2018; Yu 2018).

dDialyzable (38% over a 4-hour session [Rubino 2018]). When scheduled dose falls on a dialysis day, administer after dialysis (Heintz 2009).

>50 to <130

No dosage adjustment necessary

No dosage adjustment necessary

>25 to ≤50

1 g every 12 hours

2 g every 12 hours

10 to ≤25

500 mg every 12 hours

1 g every 12 hours

<10

500 mg every 24 hours

1 g every 24 hours

Hemodialysis, intermittent (thrice weekly)d

500 mg every 24 hours

1 g every 24 hours

Peritoneal dialysis

500 mg every 24 hours

1 g every 24 hours

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically-ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Bilbao-Meseguer 2018; Udy 2010). Therapeutic drug monitoring is recommended when available; doses >6 g/day have been required in some cases to achieve therapeutic (pharmacodynamic) targets (Tröger 2012).

IV:

Extended infusion method: 2 g loading dose (infused over 30 minutes) followed by 2 g infused over 3 hours every 8 hours (Tamatsukuri 2018).

Continuous infusion method: 1 g loading dose (infused over 30 minutes) followed by 6 g/day infused over 24 hours (administered either as 2 g every 8 hours over 8 hours, or 3 g every 12 hours over 12 hours) (Ehmann 2019; Venugopalan 2018).

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations assume high-flux dialyzers and flow rates of ~1,500 to 3,000 mL/hour, unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.

CVVH/CVVHD/CVVHDF: IV:

Traditional intermittent infusion method (over 30 minutes): 1 g loading dose followed by 500 mg to 1 g every 8 hours (Beumier 2014; Burger 2018; Economou 2017; Seyler 2011; Tegeder 1999; Thalhammer 1998; Ulldemolins 2015).

Continuous infusion method: 1 g loading dose (infused over 30 minutes) followed by 1 g infused over 12 hours every 12 hours (Burger 2018; Jamal 2015; Langgartner 2008).

PIRRT (eg, slow-low efficiency hemodiafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.

Note: Dosing recommendations based on 8- to 10-hour daily PIRRT sessions with effluent rates of 4 to 5 L/hour (Lewis 2016) and 6 to 12 L/hour (Deshpande 2010).

IV: Traditional intermittent infusion method (over 30 minutes): 1 g every 12 hours (Deshpande 2010; Lewis 2016). In patients with residual diuresis (urine output ≥300 mL/day ) up to 2 g every 8 hours has been recommended (Braune 2018).

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Pediatric

(For additional information see "Meropenem: Pediatric drug information")

General dosing, susceptible infection (non-CNS): Infants, Children, and Adolescents: IV: 20 mg/kg/dose every 8 hours; maximum dose: 1,000 mg/dose; extended infusions may be needed for infections due to isolates with elevated MICs (Bradley 2019; Red Book [AAP 2018]).

Anthrax (AAP [Bradley 2014]): Infants, Children, and Adolescents: Note: Consult public health officials for event-specific recommendations; after completion of therapy, initiate antimicrobial prophylaxis to complete an antimicrobial course of 60 days from onset of illness.

Systemic, excluding meningitis: IV: 20 mg/kg/dose every 8 hours as part of an appropriate combination regimen; may switch to oral follow-up therapy when signs and symptoms of active infection are resolved; complete 14 days of therapy or until clinical improvement, whichever is longer; maximum dose: 2,000 mg/dose.

Meningitis or disseminated infection in which meningitis cannot be ruled out: IV: 40 mg/kg/dose every 8 hours as part of an appropriate combination regimen for 2 to 3 weeks or until patient is clinically stable, whichever is longer; maximum dose: 2,000 mg/dose.

Cystic fibrosis, pulmonary exacerbation: Limited data available:

Traditional intermittent infusion method: Infants, Children, and Adolescents: IV: 40 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose (Zobell 2012).

Extended infusion method: Children ≥8 years and Adolescents: IV: 40 mg/kg/dose every 8 hours infused over 3 hours; maximum dose: 2,000 mg/dose; dosing based on a pharmacokinetic and pharmacodynamic study in pediatric patients with cystic fibrosis (n=30, 8 to 17 years of age); extended infusions were more likely to obtain targets as compared to traditional infusions for minimum inhibitory concentrations ≥1 mg/L (Pettit 2016).

Note: Use of the continuous infusion method to optimize exposure has also been reported in adults and a single adolescent patient with cystic fibrosis (Kuti 2004; Zobell 2014).

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 2019; 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 in infants <3 months of age), Children, and Adolescents: IV: 40 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose (Bradley 2019; Red Book [AAP 2018]); duration should be individualized based on patient characteristics and response; treatment duration for gram-negative bacilli is a minimum of 10 to 14 days; although some experts recommend ≥21 days and at least 14 days after first negative cerebrospinal fluid culture (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).

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]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

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.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Obesity: Adult

The recommendations for dosing in obese patients are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.

Principles of body weight dosing:

Note: There are limited data on the effect of obesity on dosing requirements for meropenem. Data are available from hospitalized patients (eg, critically ill) predominantly at steady state. There appears to be minimal difference in trough concentrations or other pharmacokinetic parameters (eg, clearance, Vd) between patients who are not obese and patients with varying levels of obesity (Alobaid 2016a; Alobaid 2016b; Chung 2017). For patients with a BMI ≥25 kg/m2, one large pharmacokinetic study evaluated meropenem continuous infusions and recommended calculation of drug clearance using Cockcroft-Gault estimated CrCl (CG CrCl) with adjusted body weight (AdjBW) (Pai 2015). The effect of obesity on first-dose pharmacokinetics remains unknown.

BMI ≥ 30 kg/m2: Note: Use of traditional (intermittent) dosing in patients who are obese is generally appropriate (Alobaid 2016a; Meng 2017; expert opinion). Renal function should be calculated using CG CrCl with AdjBW metric (Pai 2015).

Traditional intermittent infusion method: IV: 2 g every 8 hours infused over 30 minutes (Alobaid 2016a; Meng 2017).

Extended infusion method: Note: Preferred for patients with life-threatening infections, infections caused by resistant pathogens with MICs approaching 2 mg/mL, or CrCl >150 mL/minute to increase likelihood of achieving therapeutic concentrations (Meng 2017; Pai 2015; expert opinion).

IV: 2 g every 8 hours infused over 3 hours (Meng 2017; Pai 2015, expert opinion). Note: May give a loading dose of 2 g over 30 minutes when rapid attainment of therapeutic drug concentrations is necessary (eg, sepsis) (Crandon 2011; SCCM [Rhodes 2017]).

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 [DSC]); 1 g (1 ea [DSC]) [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)

Generic Equivalent Available: US

Yes

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)

Administration: Adult

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: Pediatric

Parenteral:

IV push: Infants ≥3 months, Children, and Adolescents: Administer reconstituted solution (up to 1,000 mg) over 3 to 5 minutes; safety data is limited with 40 mg/kg doses up to a maximum of 2,000 mg.

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.

Extended IV infusion:

Neonates: Administer over 4 hours (Padari 2012; Shabaan 2017; van den Anker 2009).

Children and Adolescents: Administer over 3 to 4 hours (Courter 2009; Nichols 2015; Pettit 2016).

Use: Labeled Indications

Intra-abdominal infection, health care-associated or high-risk community-acquired infection: 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.

Use: Off-Label: Adult

Anthrax; Bloodstream infection (gram-negative bacteremia); Cystic fibrosis, acute pulmonary exacerbation; Diabetic foot infection, moderate to severe; Intracranial abscess (brain abscess, intracranial epidural abscess) and spinal epidural abscess; Melioidosis (Burkholderia pseudomallei infection); Neutropenic enterocolitis (typhlitis); Neutropenic fever, high-risk cancer patients; Osteomyelitis and/or discitis; Pneumonia; Prosthetic joint infection (pathogen-directed therapy for multidrug-resistant gram-negative bacilli, including P. aeruginosa); Sepsis and septic shock (broad-spectrum empiric therapy, including P. aeruginosa); Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms)

Medication Safety Issues
Sound-alike/look-alike issues:

Meropenem may be confused with ertapenem, imipenem, metroNIDAZOLE

Adverse Reactions (Significant): Considerations
CNS effects

Carbapenems, including meropenem, may cause CNS toxicity. Meropenem is associated with a lower seizure risk than imipenem/cilastatin and therefore may be preferred for certain indications (Ref). Other noteworthy CNS effects caused by meropenem include delirium, continuous epileptiform discharges, and myoclonic jerking (Ref).

Mechanism: Postulated to be due to the antagonism of the GABAA receptor binding site. C2 side chain basicity may affect seizure risk of individual antimicrobials. N-acetylation or N-methylation of the C2 cyclopentene ring can alter the basicity substitution of this ring; meropenem is less basic than imipenem-cilastatin (Ref).

Risk factors:

• Preexisting neurologic conditions (eg, seizures, stroke, brain injury) (Ref)

• Drug accumulation in kidney impairment

Clostridioides difficile infection

Clostridioides difficile infection, including Clostridioides difficile associated diarrhea, has been reported with meropenem.

Onset: Varied; may start on the first day of antibiotic therapy or up to 3 months postantibiotic (Ref).

Risk factors:

• Antibiotic exposure (highest risk factor) (Ref)

• Type of antibiotic (carbapenems among highest risk) (Ref)

• Long durations in a hospital or other health care setting (recent or current) (Ref)

• Older adults (Ref)

• Immunocompromised conditions (Ref)

• A serious underlying condition (Ref)

• GI surgery/manipulation (Ref)

• Antiulcer medications (eg, proton pump inhibitors and H2 blockers) (Ref)

• Chemotherapy (Ref)

Hypersensitivity reactions (immediate and delayed)

Immediate (including anaphylaxis, angioedema, and urticaria) (Ref) and delayed hypersensitivity reactions have been reported. Delayed hypersensitivity reactions range from skin rash to rare severe cutaneous adverse reactions (SCARs), including acute generalized exanthematous pustulosis (AGEP) (Ref), drug reaction with eosinophilia and systemic symptoms (Ref), Stevens-Johnson syndrome (Ref), and toxic epidermal necrolysis (Ref).

Mechanism: Non-dose-related; immunologic. Immediate hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria) are IgE-mediated (Ref). Delayed hypersensitivity reactions, including maculopapular rash and SCARs, are mediated by T-cells (Ref).

Onset: Immediate hypersensitivity reactions: Rapid; IgE-mediated reactions (anaphylaxis, angioedema, urticaria) generally occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). Delayed hypersensitivity reactions: Varied; maculopapular reactions typically occur 6 to 10 days after initiation. Other delayed hypersensitivity reactions, including SCARs, generally manifest after 1 to 8 weeks after initiation (although the onset of these reactions may be delayed up to 3 months) (Ref). AGEP has been reported to occur within 24 hours after initiation of meropenem (Ref).

Risk Factors:

• Previous hypersensitivity to penicillin/cephalosporins and carbapenems: Cross-reactivity between penicillins/cephalosporins and carbapenems is considered to be 1% or less (Ref); although cross-reactivity rates of 4.6% have been reported (Ref). Despite similar core structures, cross-reactions between carbapenems have not been well described (Ref). Some patients may tolerate alternative carbapenems following a hypersensitivity reaction to meropenem (Ref).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Cardiovascular: Acute myocardial infarction (≤1%), bradycardia (≤1%), cardiac failure (≤1%), chest pain (≤1%), hypertension (≤1%), hypotension (≤1%), peripheral edema (≤1%), peripheral vascular disease (>1%), pulmonary embolism (≤1%), shock (1%), syncope (≤1%), tachycardia (≤1%)

Dermatologic: Dermal ulcer (≤1%), diaphoresis (≤1%), pruritus (1%), skin rash (2% to 3%, includes diaper-area moniliasis in infants), urticaria (≤1%)

Endocrine & metabolic: Hypervolemia (≤1%), hypoglycemia (>1%)

Gastrointestinal: Abdominal pain (≤1%), anorexia (≤1%), constipation (1% to 7%), diarrhea (4% to 7%), dyspepsia (≤1%), enlargement of abdomen (≤1%), flatulence (≤1%), gastrointestinal disease (>1%), glossitis (1%), intestinal obstruction (≤1%), nausea (≤8%), oral candidiasis (≤2%), vomiting (≤4%)

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%)

Nervous system: Agitation (≤1%), anxiety (≤1%), chills (≤1%), confusion (≤1%), delirium (≤1%), depression (≤1%), dizziness (≤1%), drowsiness (≤1%), hallucination (≤1%), headache (2% to 8%), insomnia (≤1%), nervousness (≤1%), pain (≤5%), paresthesia (≤1%), seizure (≤1%)

Neuromuscular & skeletal: Asthenia (≤1%), back pain (≤1%)

Renal: Renal failure syndrome (≤1%)

Respiratory: Apnea (1%), asthma (≤1%), cough (≤1%), dyspnea (≤1%), hypoxia (≤1%), pharyngitis (>1%), pleural effusion (≤1%), pneumonia (>1%), pulmonary edema (≤1%), respiratory system disorder (≤1%)

Miscellaneous: Accidental injury (>1%), fever (≤1%)

<1%:

Cardiovascular: Local thrombophlebitis, localized phlebitis

Endocrine & metabolic: Edema at insertion site

Gastrointestinal: Gastrointestinal hemorrhage, melena

Hematologic & oncologic: Hemoperitoneum

Local: Injection site reaction, pain at injection site

Respiratory: Epistaxis

Frequency not defined:

Endocrine & metabolic: Hypokalemia, increased lactate dehydrogenase

Genitourinary: Hematuria

Hematologic & oncologic: Decreased partial thromboplastin time, decreased prothrombin time, eosinophilia, quantitative disorders of platelets

Postmarketing:

Dermatologic: Acute generalized exanthematous pustulosis (Ghoshal 2015), erythema multiforme, Stevens-Johnson syndrome (Sameed 2019), toxic epidermal necrolysis (Paquet 2002)

Gastrointestinal: Clostridioides difficile associated diarrhea (Xie 2018)

Hematologic & oncologic: Agranulocytosis, hemolytic anemia (Oka 2015), leukopenia, neutropenia (Van Tuyl 2016), positive direct Coombs test, positive indirect Coombs test, thrombocytopenia (Huang 2017; Khan 2014)

Hypersensitivity: Anaphylaxis (Gil-Serrano 2019), angioedema

Immunologic: Drug reaction with eosinophilia and systemic symptoms (Prados-Castano 2015)

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:

• Superinfection: Prolonged use may result in fungal or bacterial superinfection.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required in patients with CrCl ≤50 mL/minute. Thrombocytopenia has been reported in patients with renal impairment.

Special populations:

• Elderly: Lower doses (based upon renal function) are often required in the elderly.

Metabolism/Transport Effects

None known.

Drug 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: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. 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

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).

Dietary Considerations

Some products may contain sodium.

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. During outpatient use, monitor for neuromotor impairment and mental alertness.

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 and Pharmacokinetics

Distribution: Penetrates into most tissues and body fluids including urinary tract, peritoneal fluid, bone, bile, lung, bronchial mucosa, muscle tissue, heart valves (Craig 1997; Nicolau 2008), and CSF (CSF penetration: Neonates and infants ≤3 months of age: 70%).

Vd:

Neonates and infants ≤3 months of age: 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 of age: Median: 2.7 hours; range: 1.6 to 3.8 hours (Smith 2011).

Infants and children 3 months to 2 years of age: 1.5 hours.

Children 2 to 12 years of age 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 of age: 0.12 L/hour/kg (Smith 2011).

Infants and children: 0.26 to 0.37 L/hour/kg (Blumer 1995).

Pharmacodynamics and Pharmacokinetics: Additional Considerations

Renal function impairment: Clearance correlates with CrCl in patients with renal impairment.

Geriatric: Reduction in plasma clearance correlates with age-associated reduction in CrCl (Craig 1997).

Anti-infective considerations:

Parameters associated with efficacy: Time dependent, associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC).

Organism specific:

Gram-negative organisms (eg, E. coli, P. aeruginosa): Goal: ≥40% fT > MIC (bactericidal) (Drusano 2003; Mattoes 2004; Nicolau 2008; Ong 2007).

Population specific:

Critically ill patients in the ICU: Minimum goal: ≥50% fT > MIC; preferred goal: ≥100% fT > MIC (Abdul-Aziz 2020; Al-Shaer 2020; Roberts 2014); some experts favor ≥100% fT >4 times the MIC (Guilhaumou 2019).

Patients with cystic fibrosis: Goal: >65% fT > MIC (Kuti 2018).

Expected drug exposure in patients with normal renal function:

Infants and Children 2 months to 12 years of age: Cmax (peak): IV:

30-minute infusion, single-dose, hospitalized patients:

20 mg/kg (maximum dose: 1 g): 56.9 mg/L (Blumer 1995).

40 mg/kg (maximum dose: 1 g): 92.1 mg/L (Blumer 1995).

Adults: Cmax (peak): IV:

30-minute infusion, healthy volunteers:

500 mg, single dose: ~23 mg/L (range: 14 to 26 mg/L).

1 g, single dose: ~49 mg/L (range: 39 to 58 mg/L).

3-hour infusion, critically ill patients:

1 g, post first dose: 15.36 ± 1.11 mg/L (Kothekar 2020).

1 g, steady state: 14.14 ± 2.02 mg/L (Kothekar 2020).

Postantibiotic effect: Minimal postantibiotic effect; varies based on the organism:

P. aeruginosa, S. aureus, and Enterobacteriaceae: <2 hours (Bowker 1996; Nadler 1989).

Parameters associated with toxicity: In a retrospective study, trough concentrations (Cmin) of >64.2 mg/L and >44.5 mg/L were associated with neurotoxicity or nephrotoxicity, respectively (Imani 2017).

Pricing: US

Solution (reconstituted) (Meropenem Intravenous)

1 g (per each): $8.53 - $52.00

500 mg (per each): $4.54 - $26.00

Solution (reconstituted) (Meropenem-Sodium Chloride Intravenous)

1 gm/50 mL (per each): $29.79

500 mg/50 mL (per each): $21.28

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.

Brand Names: International
  • Accurem (TH);
  • Acus (CL);
  • Archifar (HR, MT, SG);
  • Aris (UA);
  • Bestinem (ZW);
  • Biopenem (AR);
  • 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);
  • Mepenox (BR);
  • Merant (AR);
  • Mercide (ZA);
  • Mero (TH);
  • Merofen (ID);
  • Merogram (TZ);
  • Meroject (ZA);
  • Meromax (PH);
  • Meronem (AE, BD, BE, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CL, CR, CU, CY, CZ, DE, DO, EE, EG, ES, ET, FI, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, IE, IL, IN, IS, JM, JO, KE, LB, LR, LT, LU, MA, ML, MR, MT, MU, MW, MY, NE, NG, NI, NL, PA, 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);
  • Meropen (JP, KR, LK, PH);
  • Meropevex (PH);
  • Meroponia (IE);
  • Merosan (ID);
  • Merospira (DK);
  • Merostarkyl (EG);
  • Merovex (PH);
  • Meroxi (ID);
  • Merozan (PH);
  • Merozen (PY);
  • Merpem (AR);
  • Merrem (BB, IT, MX);
  • Mirage (EG);
  • Monan (ZW);
  • Monem (LK, MY, TH);
  • Myron (TW);
  • Newropenem (KR);
  • Opimer (ID);
  • Penem (ID);
  • Penembact (NZ);
  • Penomer (LK);
  • Pisapem (EC);
  • Pospenem (KR);
  • Pronem (VE);
  • Propenem (ID);
  • Romenem (TH);
  • Ronem (ID, UA, ZW);
  • Ropen (PH);
  • Ropenn (AU);
  • Tripenem (ID, MY);
  • Zaxter (TH, VE)


For country abbreviations used in Lexicomp (show table)

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