hypersensitivity reactions, including maculopapular rash and SCARs, are mediated by T-

cells (Blumenthal 2019).

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 (Blumenthal 2019). 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) (Blumenthal 2019, Brockow 2015, NICE 2014). AGEP has
been reported to occur within 24 hours after initiation of meropenem (Ghoshal 2015,
Khalel 2010).

Risk Factors:

• Previous hypersensitivity to penicillin/cephalosporins and carbapenems: Cross-

reactivity between penicillins/cephalosporins and carbapenems is considered to be
1% or less (Gaeta 2015, Romano 2007, Romano 2010); although cross-reactivity
rates of 4.6% have been reported (Al-Ahmad 2018). Despite similar core structures,
cross-reactions between carbapenems have not been well described (Lee 2019).
Some patients may tolerate alternative carbapenems following a hypersensitivity
reaction to meropenem (Gil-Serrano 2019, Morgado 2020, Noguerado-Mellado
2014).

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

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:

• 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.

Special populations:

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

Metabolism/Transport Effects
None known.

Drug Interactions
(For additional information: Launch drug interactions program)

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.

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), 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 and Pharmacokinetics: 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)

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

Solution (reconstituted) (Merrem Intravenous)

500 mg (per each): $17.48

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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REFERENCES
1. Ahmed N, Jen SP, Altshuler D, Papadopoulos J, Pham VP, Dubrovskaya Y. Evaluation of meropenem extended
versus intermittent infusion dosing protocol in critically ill patients [January 1, 2018]. J Intensive Care Med.
doi:10.1177/0885066618784264 [PubMed 29954243]

2. Al-Ahmad M, Rodriguez-Bouza T. Drug allergy evaluation for betalactam hypersensitivity: Cross-reactivity with
cephalosporines, carbapenems and negative predictive value. Asian Pac J Allergy Immunol. 2018;36(1):27-31.
doi:10.12932/AP0853 [PubMed 28577519]