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Pronunciation
(mer oh PEN em)
Generic Available (U.S.)
Yes
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of intra-abdominal infections (complicated appendicitis and peritonitis); treatment of bacterial meningitis in pediatric patients ≥3 months of age caused by S. pneumoniae, H. influenzae, and N. meningitidis; treatment of complicated skin and skin structure infections caused by susceptible organisms
Canadian labeling: Additional indications (not in U.S. labeling): Treatment of lower respiratory tract infections (community-acquired and nosocomial pneumonias), complicated urinary tract infections, gynecologic infections (excluding chlamydia), and septicemia; treatment of bacterial meningitis in adults caused by S. pneumoniae, H. influenzae, and N. meningitidis (use in adult meningitis based on pediatric data)
Use: Unlabeled
Burkholderia pseudomallei (melioidosis), febrile neutropenia, liver abscess, otitis externa
Pregnancy Risk Factor
B
Pregnancy Considerations
Meropenem is classified as pregnancy category B because no evidence of impaired fertility or fetal harm has been found in animals. Adequate and well-controlled studies have not been conducted in pregnant women and it is not known whether meropenem can cause fetal harm.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
It is not known if meropenem is excreted in breast milk. The manufacturer recommends that caution be exercised when administering meropenem to breast-feeding women. Most penicillins and carbapenems are safe for use in breast-feeding. Nondose-related effects could include modification of bowel flora.
Contraindications
Hypersensitivity to meropenem, any component of the formulation, or other carbapenems (eg, doripenem, ertapenem, imipenem); patients who have experienced anaphylactic reactions to other 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.
• 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 moderate-to-severe renal dysfunction. Increased seizure risk and thrombocytopenia have been reported in patients with renal dysfunction.
Concurrent drug therapy issues:
• Valproic acid and derivatives: Carbapenems, including meropenem, may decrease the serum concentration of divalproex sodium/valproic acid increasing the risk of breakthrough seizures. Concurrent use of carbapenem antibiotics with divalproex sodium/valproic acid is generally not recommended. Alternative antimicrobial agents should be considered, but if a concurrent carbapenem is necessary, consider additional antiseizure medication.
Special populations:
• Elderly: Lower doses (based upon renal function) are often required in the elderly.
Adverse Reactions
1% to 10%:
Central nervous system: Headache (2% to 8%), pain (≤5%)
Dermatologic: Rash (2% to 3%, includes diaper-area moniliasis in infants), pruritus (1%)
Endocrine & metabolic: Hypoglycemia
Gastrointestinal: Diarrhea (4% to 7%), nausea/vomiting (1% to 8%), constipation (1% to 7%), oral moniliasis (up to 2% in pediatric patients), glossitis (1%)
Hematologic: Anemia (≤6%)
Local: Inflammation at the injection site (2%), phlebitis/thrombophlebitis (1%), injection site reaction (1%)
Respiratory: Apnea (1%), pharyngitis, pneumonia
Miscellaneous: Sepsis (2%), shock (1%)
<1%: Abdominal enlargement, abdominal pain, agitation/delirium, alkaline phosphatase increased, ALT increased, AST increased, anemia (hypochromic), anorexia, anxiety, aPTT decreased, asthma, back pain, bilirubin increased, bradycardia, BUN increased, cardiac arrest, chest pain, chills, cholestatic jaundice/jaundice, confusion, cough, creatinine increased, depression, diaphoresis, dizziness, dyspepsia, dyspnea, dysuria, eosinophilia, epistaxis, fever, flatulence, gastrointestinal hemorrhage, hallucinations, heart failure, hematuria, hemoglobin/hematocrit decreased, hemoperitoneum, hepatic failure, hyper-/hypotension, hypervolemia, hypokalemia, hypoxia, injection site edema, injection site pain, ileus, insomnia, intestinal obstruction, LDH increased, leukocytosis, melena, MI, nervousness, paresthesia, pelvic pain, peripheral edema, platelets decreased/increased, pleural effusion, PT decreased, pulmonary edema, pulmonary embolism, renal failure, respiratory disorder, seizure, skin ulcer, somnolence, syncope, tachycardia, urinary incontinence, urticaria, vaginal moniliasis, weakness, WBC decreased, whole body pain
Postmarketing and/or case reports: Agranulocytosis, angioedema, erythema multiforme, hemolytic anemia, leukopenia, neutropenia, positive Coombs test, Stevens-Johnson syndrome, toxic epidermal necrolysis
Metabolism/Transport Effects
None known.
Drug Interactions
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Divalproex: Carbapenems may decrease the serum concentration of Divalproex. Management: Concurrent use of carbapenem antibiotics with divalproex 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
Probenecid: May increase the serum concentration of Meropenem. Risk X: Avoid combination
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 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Valproic Acid: Carbapenems may decrease the serum concentration of Valproic Acid. 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
Storage
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 2 hours at controlled room temperature of 15°C to 25°C (59°F to 77°F) or for up to 12 hours under refrigeration.
Sodium chloride: Stable for up to 2 hours at controlled room temperature of 15°C to 25°C (59°F to 77°F) or for up to 18 hours under refrigeration.
Dextrose 5% injection: Stable for 1 hour at controlled room temperature of 15°C to 25°C (59°F to 77°F) or for 8 hours under refrigeration.
Infusion admixture (1-20 mg/mL): Solution stability when diluted in NS is 4 hours at controlled room temperature of 15°C to 25°C (59°F to 77°F) or 24 hours under refrigeration. Stability in D5W is 1 hour at controlled room temperature of 15°C to 25°C (59°F to 77°F) or for 4 hours under refrigeration. For other diluents, see prescribing information.
Reconstitution
Meropenem infusion vials may be reconstituted with SWFI or a compatible diluent (eg, NS). The 500 mg vials should be reconstituted with 10 mL, and 1 g vials with 20 mL. May be further diluted with compatible solutions for infusion. Consult detailed reference/product labeling for compatibility.
Compatibility
Stable in NS for 4 hours at controlled room temperature and up to 24 hours refrigerated; variable stability (consult detailed reference) in D5LR, D51/4NS, D5NS, D5W, D10W, LR, 1/2NS, mannitol 2.5%, mannitol 10%, sodium bicarbonate 5%.
Y-site administration: Compatible: Aminophylline, anidulafungin, atropine, caspofungin, cimetidine, cyclosporine, dexamethasone sodium phosphate, digoxin, diphenhydramine, docetaxel, enalaprilat, fluconazole, furosemide, gentamicin, heparin, insulin (regular), linezolid, metoclopramide, milrinone, morphine, norepinephrine, phenobarbital, telavancin, vancomycin, vasopressin. Incompatible: Amphotericin B, diazepam, metronidazole, pantoprazole. Variable (consult detailed reference): Acyclovir, calcium gluconate, doxycycline, ondansetron, potassium chloride, zidovudine.
Compatibility in syringe: Incompatible with pantoprazole.
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: Vd: Adults: 15-20 L, Children: 0.3-0.4 L/kg; penetrates well into most body fluids and tissues; CSF concentrations approximate those of the plasma
Protein binding: ~2%
Metabolism: Hepatic; metabolized to open beta-lactam form (inactive)
Half-life elimination:
Normal renal function: 1-1.5 hours
Clcr 30-80 mL/minute: 1.9-3.3 hours
Clcr 2-30 mL/minute: 3.82-5.7 hours
Time to peak, tissue: 1 hour following infusion
Excretion: Urine (~70% as unchanged drug)
Dosage
Usual dosage ranges:
Children ≥3 months: I.V.: 30-120 mg/kg/day divided every 8 hours (maximum dose: 6 g/day)
Adults: I.V.: 1.5-6 g/day divided every 8 hours
Extended infusion method (unlabeled dosing): I.V.: 0.5-2 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.
Indication-specific dosing:
Children ≥3 months (<50 kg): I.V.:
Febrile neutropenia (unlabeled use): 20 mg/kg every 8 hours (maximum dose: 1 g every 8 hours)
Intra-abdominal infections (complicated): 20 mg/kg every 8 hours (maximum dose: 1 g every 8 hours)
Meningitis: 40 mg/kg every 8 hours (maximum dose: 2 g every 8 hours)
Pneumonia (community-acquired): Canadian labeling (not in U.S. labeling): 10-20 mg/kg every 8 hours (maximum dose: 1 g every 8 hours)
Skin and skin structure infections:
Complicated: U.S. labeling: 10 mg/kg every 8 hours (maximum dose: 500 mg every 8 hours)
Uncomplicated: Canadian labeling (not in U.S. labeling): 10-20 mg/kg every 8 hours (maximum dose: 1 g every 8 hours)
Urinary tract infection (complicated): Canadian labeling (not in U.S. labeling): 10 mg/kg every 8 hours (maximum dose: 500 mg every 8 hours)
Children >50 kg and Adults: I.V.:
Burkholderia pseudomallei
(melioidosis) (unlabeled use),
Pseudomonas:
1 g every 8 hours
Cholangitis, intra-abdominal infections, complicated: 1 g every 8 hours. Note: 2010 IDSA guidelines recommend treatment duration of 4-7 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).
Febrile neutropenia, otitis externa, pneumonia (unlabeled uses): 1 g every 8 hours
Liver abscess (unlabeled use): 1 g every 8 hours for 2-3 weeks, then oral therapy for duration of 4-6 weeks
Meningitis: Canadian labeling (not in U.S. labeling): 2 g every 8 hours
Mild-to-moderate infection, other severe infections (unlabeled use): 1.5-3 g/day divided every 8 hours
Pneumonia (community-acquired): Canadian labeling (not in U.S. labeling): 500 mg every 8 hours
Skin and skin structure infections:
Complicated: U.S. labeling: 500 mg every 8 hours; diabetic foot: 1 g every 8 hours
Uncomplicated: Canadian labeling (not in U.S. labeling): 500 mg every 8 hours
Urinary tract infections (complicated): Canadian labeling (not in U.S. labeling): 500 mg every 8 hours. Note: Up to 1 g every 8 hours may be administered (Pallett, 2010).
Adults: Canadian labeling (not in U.S. labeling): I.V.:
Gynecologic and pelvic inflammatory disease: 500 mg every 8 hours
Pneumonia (nosocomial): 1 g every 8 hours
Septicemia: 1 g every 8 hours
Dosing adjustment in renal impairment:
Children
(unlabeled dosing; Aronoff, 2007):
GFR 30-50 mL/minute: Administer 20-40 mg/kg every 12 hours
GFR 10-29 mL/minute: Administer 10-20 mg/kg every 12 hours
GFR <10 mL/minute: Administer 10-20 mg/kg every 24 hours
Intermittent hemodialysis (IHD): 10-20 mg/kg every 24 hours (administer after hemodialysis on dialysis days)
Peritoneal dialysis (PD): 10-20 mg/kg every 24 hours
Continuous renal replacement therapy (CRRT): 20-40 mg/kg every 12 hours
Adults:
Clcr 26-50 mL/minute: Administer recommended dose based on indication every 12 hours
Clcr 10-25 mL/minute: Administer one-half recommended dose based on indication every 12 hours
Clcr <10 mL/minute: Administer one-half recommended dose based on indication every 24 hours
Alternative dosing recommendations: (unlabeled dosing; Aronoff, 2007):
GFR 10-50 mL/minute: Administer recommended dose (based on indication) every 12 hours
GFR <10 mL/minute: Administer recommended dose (based on indication) every 24 hours
Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): Meropenem and its metabolite are readily dialyzable: 500 mg every 24 hours. Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions.
Peritoneal dialysis (unlabeled dose): Administer recommended dose (based on indication) every 24 hours (Aronoff, 2007).
Continuous renal replacement therapy (CRRT) (Heintz, 2009; 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 1-2 L/hour and minimal residual renal function) and should not supersede clinical judgment:
CVVH: Loading dose of 1 g followed by either 0.5 g every 8 hours or 1 g every 12 hours
CVVHD/CVVHDF: Loading dose of 1 g followed by either 0.5 g every 6-8 hours or 1 g every 8-12 hours
Note: Consider giving patients receiving CVVHDF dosages of 750 mg every 8 hours or 1500 mg every 12 hours (Heintz, 2009). Substantial variability exists in various published recommendations, ranging from 1-3 g/day in 2-3 divided doses. One gram every 12 hours achieves a target trough of ~4 mg/L.
Administration: I.V.
Administer I.V. infusion over 15-30 minutes; I.V. bolus injection (5-20 mL) over 3-5 minutes
Extended infusion administration (unlabeled dosing): Administer over 3 hours (Crandon 2011; Dandekar, 2003). Note: Must consider meropenem's limited room temperature stability if using extended infusions
Administration: I.V. Detail
pH: 7.3-8.3
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.
Test Interactions
Positive Coombs' [direct]
Dietary Considerations
Some products may contain sodium.
Patient Education
This medication can only be given by infusion. Report immediately any burning, pain, swelling, or redness at infusion site. Maintain adequate hydration unless instructed to restrict fluid intake. May cause nausea, vomiting, diarrhea, or headache. Report persistent GI distress, persistent diarrhea, mouth sores, respiratory difficulty, headache, or CNS changes (agitation, delirium).
Geriatric Considerations
Adjust dose based on renal function.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Oral moniliasis (pediatric patients) and glossitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May rarely cause agitation, confusion, insomnia, hallucinations, or depression
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Assess results of culture and sensitivity tests and patient's allergy history prior to beginning treatment. Use caution in presence of renal impairment or neurologic disorder. Infusion site should be monitored closely for phlebitis/thrombophlebitis. Assess renal and hepatic function and CBC. Teach patient importance of adequate hydration.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 500 mg, 1 g
Merrem® I.V.: 500 mg [contains sodium 45.1 mg as sodium carbonate (1.96 mEq)]
Merrem® I.V.: 1 g [contains sodium 90.2 mg as sodium carbonate (3.92 mEq)]
Pricing: U.S. (www.drugstore.com)
Solution (reconstituted) (Meropenem)
500 mg (1): $29.99
Solution (reconstituted) (Merrem)
1 g (1): $79.56
500 mg (1): $39.99
References
American Thoracic Society and Infectious Diseases Society of America, “Guidelines for the Management of Adults With Hospital-Acquired, Ventilator-Associated, and Healthcare-Associated Pneumonia,” Am J Respir Crit Care Med, 2005, 171(4):388-416.
Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007, p 61, 153.
Baldwin CM, Lyseng-Williamson KA, and Keam SJ, “Meropenem: A Review of Its Use in the Treatment of Serious Bacterial Infections,” Drugs, 2008, 68(6):803-38.
Blummer JL, Reed MD, Kearns GL, et al, “Sequential, Single-Dose Pharmacokinetic Evaluation of Meropenem in Hospitalized Infants and Children,” Antimicrob Agents Chemother, 1995, 39(8):1721-5.
Bradley, JS, “Meropenem: A New, Extremely Broad Spectrum Beta-lactam Antibiotic for Serious Infections in Pediatrics,” Pediatr Infect Dis J, 1997, 16:263-8.
Craig WA, “The Pharmacology of Meropenem, a New Carbapenem Antibiotic,” Clin Infect Dis, 1997, 24(Suppl 2):266-75.
Crandon JL, Ariano RE, Zelenitsky SA, et al, “Optimization of Meropenem Dosage in the Critically Ill Population Based on Renal Function,” Intensive Care Med, 2011, 37(4):632-8.
Dandekar PK, Maglio D, Sutherland CA, et al, “Pharmacokinetics of Meropenem 0.5 and 2 g Every 8 Hours as a 3-Hour Infusion," Pharmacotherapy 2003, 23(8):988-91.
Fish DN and Singletary TJ, “Meropenem, A New Carbapenem Antibiotic,” Pharmacotherapy, 1997, 17(4):644-69.
Gould FK, Denning DW, Elliott TS, et al, “Guidelines for the Diagnosis and Antibiotic Treatment of Endocarditis in Adults: A Report of the Working Party of the British Society for Antimicrobial Chemotherapy,” J Antimicrob Chemother, 2012, 67(2):269-89.
Hellinger WC and Brewer NS, “Carbapenems and Monobactams: Imipenem, Meropenem, and Aztreonam,” Mayo Clin Proc, 1999, 74(4):420-34.
Heintz BH, Matzke GR, Dager WE, “Antimicrobial Dosing Concepts and Recommendations for Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis,” Pharmacotherapy, 2009, 29(5):562-77.
Krueger WA, Schroeder TH, Hutchison M, et al, “Pharmacokinetics of Meropenem in Critically Ill Patients With Acute Renal Failure Treated by Continuous Hemodiafiltration,” Antimicrob Agents Chemother, 1998, 42(9):2421-4.
Linden P, “Safety Profile of Meropenem: An Updated Review of Over 6,000 Patients Treated With Meropenem,” Drug Saf, 2007, 30(8):657-68.
Ljungberg B and Nilsson-Ehle I, “Pharmacokinetics of Meropenem an Its Metabolites in Young and Elderly Healthy Men,” Antimicrob Agents Chemother, 1992, 36(7):1437-40.
Nicolau DP, “Pharmacodynamic Optimization of Beta-lactams in the Patient Care Setting,” Critical Care, 2008, 12(Suppl 4):2.
Pallett A and Hand K, “Complicated Urinary Tract Infections: Practical Solutions for the Treatment of Multiresistant Gram-Negative Bacteria,” J Antimicrob Chemother, 2010, 65(Suppl 3):25-33.
Solomkin JS, Mazuski JE, Bradley JS, et al, “Diagnosis and Management of Complicated Intra-Abdominal Infections in Adults and Children: Guidelines by the Surgical Infection Society and the Infectious Diseases Society of America,” Clin Infect Dis, 2010, 50(2):133-64.
Trotman RL, Williamson JC, Shoemaker DM, et al, "Antibiotic Dosing in Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy," Clin Infect Dis, 2005, 41(8):1159-66.
Tunkel AR, Hartman BJ, Kaplan SL, et al, “Practice Guidelines for the Management of Bacterial Meningitis,” Clin Infect Dis, 2004, 39(9):1267-84.
Ververs TF, van Dijk A, Vinks SA, et al, “Pharmacokinetics and Dosing Regimen of Meropenem in Critically Ill Patients Receiving Continuous Venovenous Hemofiltration,” Crit Care Med, 2000, 28(10):3412-6.
Wiseman LR, Wagstaff AJ, Brogden RN, et al, “Meropenem. A Review of its Antibacterial Activity, Pharmacokinetic Properties and Clinical Efficacy,” Drugs, 1995, 50(1):73-101.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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