Meropenem
J01D - Other beta-lactam antibacterials
ATC J01DH02
Small molecule
approved 1996
Parenteral
Natural product
🧬 Cross-allergy: Carbapenems
JFDA label: Merolab 500mg I.V Powder for Solution
Mechanism of Action
Inhibitor of Bacterial penicillin-binding protein — Bacterial penicillin-binding protein inhibitor
| Target | Action | Gene / class |
|---|---|---|
| Bacterial penicillin-binding protein efficacy | INHIBITOR |
Indications
Approved
- Bacterial meningitis
- Intra-abdominal infections
- Skin and skin structure infections, complicated
Off-label
- Bacterital meningitis
- Catheter-related blood stream infections
- Cystic fibrosis, pulmonary exacerbation
- Febrile neutropenia
- Gynecologic and pelvis infection
- Melioidosis (Burkholderia pseudomallei)
- Pneumonia, hospital-acquired or ventilator-associated
- Prosthetic joint infection
- Skin and soft tissue necrotizing infections
- Surgical site Infection
- Urinary tract infection
Antimicrobial Spectrum
Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: EUCAST v16 · curated · openfda-label.
Bacteria
| Organism | Activity | MIC |
|---|---|---|
| Acinetobacter baumannii | Susceptible | 2.0 mg/L |
| Acinetobacter spp. | Susceptible | 2.0 mg/L |
| Anaerobes | Susceptible | 1.0 mg/L |
| Bacillus spp. | Susceptible | 0.25 mg/L |
| Bacteroides fragilis | Active | — |
| Bacteroides ovatus | Active | — |
| Bacteroides thetaiotaomicron | Active | — |
| Bacteroides uniformis | Active | — |
| Bacteroides ureolyticus | Active | — |
| Bacteroides vulgatus | Active | — |
| Burkholderia cepacia complex | Susceptible | 8.0 mg/L |
| Campylobacter jejuni | Active | — |
| Citrobacter freundii | Active | — |
| Citrobacter koseri | Active | — |
| Clostridium difficile | Active | — |
| Clostridium perfringens | Active | — |
| Enterobacter cloacae | Susceptible | 2.0 mg/L |
| Enterobacterales | Susceptible | 2.0 mg/L |
| Enterococcus faecalis | Active | — |
| Escherichia coli | Susceptible | 2.0 mg/L |
| Haemophilus influenzae | Susceptible | 2.0 mg/L |
| Klebsiella oxytoca | Active | — |
| Klebsiella pneumoniae | Susceptible | 2.0 mg/L |
| Listeria monocytogenes | Susceptible | 0.25 mg/L |
| Moraxella catarrhalis | Susceptible | 2.0 mg/L |
| Morganella morganii | Active | — |
| Neisseria meningitidis | Susceptible | 0.25 mg/L |
| Pasteurella multocida | Active | — |
| Prevotella bivia | Active | — |
| Prevotella intermedia | Active | — |
| Prevotella melaninogenica | Active | — |
| Proteus mirabilis | Active | — |
| Proteus vulgaris | Active | — |
| Pseudomonas aeruginosa | Susceptible | 2.0 mg/L |
| Pseudomonas aeruginosa | Susceptible | 82.0 mg/L |
| Serratia marcescens | Active | — |
| Staphylococcus aureus | Active | — |
| Staphylococcus epidermidis | Active | — |
| Streptococcus agalactiae | Active | — |
| Streptococcus pneumoniae | Susceptible | 2.0 mg/L |
| Streptococcus pyogenes | Active | — |
| Vibrio spp. | Susceptible | 0.5 mg/L |
| Viridans group streptococci | Susceptible | 2.0 mg/L |
| Acinetobacter baumannii | Resistant | 8.0 mg/L |
| Escherichia coli | Resistant | 8.0 mg/L |
| Klebsiella pneumoniae | Resistant | 8.0 mg/L |
| Pseudomonas aeruginosa | Resistant | 8.0 mg/L |
Class profile
| gramStatus | Both |
|---|---|
| spectrumBreadth | Extended |
| atypicalCoverage | No |
| isBactericidal | 1 |
| moaCategory | Cell wall synthesis inhibitor (beta-lactam, carbapenem) |
| pdIndex | Time-dependent |
| postAntibioticEffect | Short |
| mrsaCoverage | 0 |
| resistanceMechanisms | Carbapenemase (KPC,NDM,OXA-48),OprD porin loss,Efflux pumps |
Contraindications
Source: Lexicomp
- Hypersensitivity to meropenem, other drugs in the same class, or any component of the formulation Absolute
- patients who have experienced anaphylactic reactions to beta-lactams Absolute
Adverse Reactions
Very Common >10%Common 1–10%Uncommon 0.1–1%
Rare 0.01–0.1%Very Rare <0.01%Not Known
Cardiac disorders (13)
Common bradycardia · cardiac arrest · cardiac failure · chest pain · hypertension · hypotension · myocardial infarction · peripheral edema · Peripheral vascular disease · pulmonary embolism · shock · syncope · tachycardia
Nervous system disorders (2)
Common convulsions, pruritus, dermal ulcer, diaphoresis, urticaria · Headache
Hepatobiliary disorders (1)
Common Hyperbilirubinemia
Renal and urinary disorders (5)
Common Dysuria · pelvic pain · Renal failure · urinary incontinence · vulvovaginal candidiasis
Blood and lymphatic system disorders (2)
Common Anemia · hypochromic anemia
Metabolism and nutrition disorders (2)
Common hypervolemia · Hypoglycemia
Gastrointestinal disorders (13)
Common abdominal pain · anorexia · constipation · diarrhea · dyspepsia · enlargement of abdomen · flatulence · gastrointestinal disease · glossitis · intestinal obstruction · Nausea · oral candidiasis · vomiting
Musculoskeletal and connective tissue disorders (2)
Common Back pain · weakness
General disorders and administration site conditions (3)
Common Accidental injury · fever · Inflammation at injection site
Respiratory, thoracic and mediastinal disorders (10)
Common apnea · asthma · cough · dyspnea · hypoxia · Pharyngitis · pleural effusion · pneumonia · pulmonary edema · respiratory tract disease
Dosing
Source: Lexicomp
Usual dosage range: IV: 1.5 to 6 g daily divided every 8 hours Extended infusion method (off-label dosing): IV: 0.5 to 2 g over 3 hours every 8 hours (Crandon 2011; Dandekar 2003). Note: Dosing used at some centers and is based on pharmacokinetic/pharmacodynamic modeling and not clinical efficacy data. 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 (admixed with NS at a concentration of 20 mg/mL) at room temperature for ≤4 hours and under refrigeration ≤24 hours (Patel 1997). Indication-specific dosing: Bacterial meningitis (off-label use): IV: 2 g every 8 hours; duration of therapy dependent upon pathogen: N. meningitidis, H. influenza: 7 days; S. pneumoniae: 10 to 14 days; Listeria monocytogenes, aerobic gram-negative bacilli: 21 days (IDSA [Tunkel 2004]) Catheter-related bloodstream infections (off-label use): IV: 1 g every 8 hours (Mermel 2009) Cholangitis, intra-abdominal infections, complicated: IV: 1 g every 8 hours. Note: 2010 IDSA guidelines recommend treatment duration of 4 to 7 days (provided source controlled). Not recommended for mild-to-moderate, community-acquired intra-abdominal infections due to risk of toxicity and the development of resistant organisms (Solomkin 2010). Cystic fibrosis, pulmonary exacerbation (off-label use): IV: 2 g every 8 hours (Chmiel 2014) Febrile neutropenia (off-label use): IV: 1 g every 8 hours (Ohata 2011; Paul 2010) Gynecologic and pelvic infections (off-label use): IV: 500 mg every 8 hours (Hemsell 1997; Maggioni 1998) Melioidosis (Burkholderia pseudomallei) (off-label use): IV: Initial treatment (intensive-phase): 1 g every 8 hours (Cheng 2004; Inglis 2006; Lipsitz 2012). Note: Meropenem is an alternative treatment to ceftazidime for melioidosis; continued treatment with oral antibiotics is recommended after intensive-phase is completed (Lipsitz 2012). Pneumonia (hospital-acquired, healthcare-associated, or ventilator-associated) (off-label use): IV: 1 g every 8 hours (ATS/IDSA 2005) Prosthetic joint infection, Pseudomonas aeruginosa (off-label use): IV: 1 g every 8 hours for 4 to 6 weeks (consider addition of aminoglycoside) (IDSA [Osmon 2013]) Skin and skin structure infections, complicated: IV: Pseudomonas aeruginosa-suspected or confirmed: 1 g every 8 hours Pseudomonas aeruginosa not suspected: 500 mg every 8 hours Skin and soft tissue necrotizing infections (off-label use): IV: 1 g every 8 hours in combination with an agent effective against MRSA (eg, vancomycin, linezolid, daptomycin) for empiric therapy of polymicrobial (mixed) infections. Continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (IDSA [Stevens 2014]). Surgical site infection (intestinal or genitourinary tract surgery) (off-label use): IV: 1 g every 8 hours (IDSA [Stevens 2014]) Urinary tract infect
(For additional information see "Meropenem: Pediatric drug information") Usual dosage range: Infants Gestational age Postnatal age Postnatal age ≥14 days: 20 mg/kg/dose every 8 hours Gestational age ≥32 weeks: Postnatal age Postnatal age ≥14 days: 30 mg/kg/dose every 8 hours Infants ≥3 months, Children, and Adolescents (≤50 kg): IV: 30 to 120 mg/kg/day divided every 8 hours (maximum dose: 6 g daily) Children and Adolescents (>50 kg): IV: 1.5 to 6 g daily divided every 8 hours Indication-specific dosing: Catheter-related blood stream infections (off-label use): IV: Infants ≥3 months, Children, and Adolescents (≤50 kg): IV: 20 mg/kg every 8 hours; maximum single dose: 1,000 mg (Mermel 2009) Children and Adolescents (>50 kg): Refer to adult dosing. Cholangitis, intra-abdominal infections, complicated: IV: Children and Adolescents (>50 kg): Refer to adult dosing. Cystic fibrosis, pulmonary exacerbation (off-label use): IV: Infants ≥3 months, Children, and Adolescents (≤50 kg): 40 mg/kg every 8 hours; maximum single dose: 2,000 mg (Zobell 2012) Children and Adolescents (>50 kg): Refer to adult dosing. Febrile neutropenia (off-label use): IV: Infants ≥3 months, Children, and Adolescents (≤50 kg): 20 mg/kg every 8 hours (maximum dose: 1,000 mg every 8 hours) (Lehrnbecher 2012; Yildirim 2008) Children and Adolescents (>50 kg): Refer to adult dosing. Intra-abdominal infections (complicated): IV: Infants Note: Administer as an IV infusion over 30 minutes; do not administer as an IV bolus Gestational age Postnatal age Postnatal age ≥14 days: 20 mg/kg/dose every 8 hours Gestational age ≥32 weeks: Postnatal age Postnatal age ≥14 days: 30 mg/kg/dose every 8 hours Infants ≥3 months, Children, and Adolescents: 20 mg/kg every 8 hours (maximum dose: 1,000 mg every 8 hours) for 4 to 7 days (Solomkin 2010) Melioidosis (Burkholderia pseudomallei) (off-label use): IV: Infants ≥6 months, Children, and Adolescents (≤40 kg): Initial treatment (intensive-phase): 25 mg/kg (up to 1 g) every 8 hours (Cheng 2004). Note: Meropenem is an alternative treatment to ceftazidime for melioidosis; continued treatment with oral antibiotics is recommended after intensive-phase is completed (Lipsitz 2012). Children and Adolescents (>50 kg): Refer to adult dosing. Meningitis: IV: Infants ≥3 months, Children, and Adolescents (≤50 kg): 40 mg/kg every 8 hours (maximum dose: 2,000 mg every 8 hours) Children and Adolescents (>50 kg): 2 g every 8 hours Prosthetic joint infection, Pseudomonas aeruginosa (off-label use): Children and Adolescents (>50 kg): Refer to adult dosing. Skin and skin structure infections: IV: Infants ≥3 months, Children, and Adolescents (≤50 kg): Complicated: Pseudomonas aeruginosa-suspected or confirmed: 20 mg/kg every 8 hours (maximum dose: 1,000 mg every 8 hours) Pseudomonas aeruginosa not suspected: 10 mg/kg every 8 hours (maximum dose: 500 mg every 8 hours) Children and Adolescents (>50 kg): Refer to adult dosing. Skin and soft tissue necrotizing infections (off-labe
Refer to adult dosing.
Adults: 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 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 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. Children: Manufacturer’s labeling: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied) Alternate recommendations (off-label dosing; Aronoff 2007): GFR 30 to 50 mL/minute: Administer 20 to 40 mg/kg every 12 hours GFR 10 to 29 mL/minute: Administer 10 to 20 mg/kg every 12 hours GFR Intermittent hemodialysis (IHD): 10 to 20 mg/kg every 24 hours administer after hemodialysis on dialysis days) Peritoneal dialysis (PD): 10 to 20 mg/kg every 24 hours Continuous renal replacement therapy (CRRT): 20 to 40 mg/kg every 12 hours
No dosage adjustment necessary.
Warnings & Precautions
Source: Lexicomp
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.
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:
Elderly
Lower doses (based upon renal function) are often required in the elderly.
Pregnancy & Lactation
Pregnancy
FDA category B
Adverse events were not observed in animal reproduction studies. Incomplete transplacental transfer of meropenem was found using an ex vivo human perfusion model.
Lactation
Small amounts of meropenem are excreted into breast milk (case report). The manufacturer recommends that caution be exercised when administering meropenem to breastfeeding women. Nondose-related effects could include modification of bowel flora.
Monitoring
| Efficacy | Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin) |
|---|---|
| Toxicity | Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea) |
| Clinical pearl | Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship). |
| Counseling | Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h. |
Chemistry & Properties
| Formula | C17H25N3O5S |
|---|---|
| Molecular weight | 383.47 g/mol |
| IUPAC name | (4R,5S,6S)-3-[(3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]sulfanyl-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid |
| CAS | 96036-03-2 |
| PubChem CID | 441130 |
| InChIKey | DMJNNHOOLUXYBV-PQTSNVLCSA-N |
| logP | -0.31 (XLogP -2.4) |
| Polar surface area | 110.18 Ų |
| H-bond acceptors / donors | 6 / 3 |
| Drug-likeness (QED) | 0.56 |
| Lipinski violations | 0 |
SMILES
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)O)=C(S[C@@H]3CN[C@H](C(=O)N(C)C)C3)[C@H](C)[C@H]12Biology & Pharmacokinetics
Pharmacokinetics
| BBB penetrant | No |
|---|
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP2B6 | Inhibitor | — |
Transporters
ASBT (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)OAT3 (Substrate)P-gp (Substrate)
Drug–drug interactions (14, DDInter)
| Interacting drug | Severity | Management |
|---|---|---|
| Bupropion | major | |
| Iohexol | major | |
| Iopamidol | major | |
| Alpelisib | moderate | |
| Encorafenib | moderate | |
| Ethinylestradiol | moderate | |
| Lindane | moderate | |
| Mycophenolic acid | moderate | |
| Nitisinone | moderate | |
| Pemetrexed | moderate | |
| Picosulfuric acid | moderate | |
| Polyethylene glycol (3350 with electrolytes) | moderate | |
| Sodium sulfate | moderate | |
| Teriflunomide | moderate |
Registered Products (20)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| Aropem | Vial 0.5 g | 1 vial | Adonis Drug Store | — |
| Aropem | Vial 1 g | 1 vial | Adonis Drug Store | — |
| Emorpeen | Vial Meropenem 500 mg | 10 vial | AL-TAQADDOM PHARMACEUTICAL INDUSTRIES/JORDAN | — |
| Emorpeen | Vial Meropenem 1000 mg | 10 vial | AL-TAQADDOM PHARMACEUTICAL INDUSTRIES/JORDAN | — |
| Merolab 1gm Powder for solution for infusion | Infusion 1 g | 10 vial | ORIENT DRUG STORE CO | — |
| Merolab 500mg I.V Powder for Solution | Solution 500 mg | 10 vial | ORIENT DRUG STORE CO | — |
| Meronem | Powder for Injection 500 mg | 10 vial | Khoury Drug Store | — |
| Meronem Injection | Powder for Injection 1.140 g | 10 vial | Khoury Drug Store | — |
| Meropa | Vial 1000 mg | 10 vial | The Arab Pharmaceutical Manufacturing PSC/Salt | — |
| Meropa | Vial 500 mg | 10 vial | The Arab Pharmaceutical Manufacturing PSC/Salt | — |
| Meropenem Kabi | Vial 1140 mg | 10 vial | Sun Set Drug Store | — |
| Meropenem Kabi | Vial 570 mg | 10 vial | Sun Set Drug Store | — |
| Ropenem | Vial 1 g | 1 vial | Reda Jardaneh Drug Store | — |
| Vabomere | Vial (as Trihydrate) 1000 mg, 1000 mg | 6 vial | Hikma Pharmaceuticals Co.Ltd/Jordan | — |
| merozan | Vial 500 mg | 1 vial pack varies | Al Hilal Drug Store | — |
| merozan | Vial 1140 mg | 50 vial pack varies | Al Hilal Drug Store | — |
| merozan | Vial 1140 mg | 1 vial pack varies | Al Hilal Drug Store | — |
| merozan | Vial 1140 mg | 10 vial pack varies | Al Hilal Drug Store | — |
| merozan | Vial 500 mg | 10 vial pack varies | Al Hilal Drug Store | — |
| merozan | Vial 500 mg | 50 vial pack varies | Al Hilal Drug Store | — |