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Pronunciation

(mer oh PEN em)

Generic Available (U.S.)

Yes

U.S. Brand Names

• Merrem® I.V.

Canadian Brand Names

• Merrem®

Pharmacologic Category

• Antibiotic, Carbapenem

Pharmacologic Category Synonyms

• Carbapenem Antibiotic

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

Use: Unlabeled/Investigational

Burkholderia pseudomallei (melioidosis), febrile neutropenia, liver abscess, meningitis (adults), otitis externa, pneumonia, urinary tract infections

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, 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: Has been associated with CNS adverse effects, including confusional states and seizures; use caution with CNS disorders (eg, brain lesions, history of seizures, or renal impairment).

• 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 anti-seizure 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 pediatrics), 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

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

Compatible 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, atenolol, atropine, cimetidine, dexamethasone sodium phosphate, digoxin, diphenhydramine, docetaxel, enalaprilat, fluconazole, furosemide, gentamicin, heparin, insulin (regular), linezolid, metoclopramide, milrinone, morphine, norepinephrine, phenobarbital, potassium chloride, vancomycin. Incompatible: Amphotericin B, diazepam, metronidazole. Variable (consult detailed reference): Acyclovir, calcium gluconate, doxycycline, ondansetron, zidovudine.

Compatibility in syringe: Incompatible with pantoprazole.

Compatibility when admixed: Compatible: Aminophylline, atropine, cimetidine, dexamethasone sodium phosphate, dobutamine, dopamine, enalaprilat, fluconazole, furosemide, gentamicin, heparin, insulin (regular), magnesium sulfate, metoclopramide, morphine, norepinephrine, phenobarbital, ranitidine, vancomycin. Incompatible: Amphotericin B, metronidazole, multivitamins. Variable (consult detailed reference): Acyclovir, doxycycline, ondansetron, zidovudine.

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: V_d: Adults: ~0.3 L/kg, Children: 0.4-0.5 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

Cl_cr 30-80 mL/minute: 1.9-3.3 hours

Cl_cr 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:

Neonates: I.V.:

Postnatal age 0-7 days: 20 mg/kg/dose every 12 hours

Postnatal age >7 days:

Weight 1200-2000 g: 20 mg/kg/dose every 12 hours

Weight >2000 g: 20 mg/kg/dose every 8 hours

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

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: 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)

Skin and skin structure infections (complicated): 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, severe: I.V.: 1 g every 8 hours. Note: 2010 IDSA guidelines recommend a 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 (unlabeled use): 2 g every 8 hours

Mild-to-moderate infection, other severe infections (unlabeled use): 1.5-3 g/day divided every 8 hours

Skin and skin structure infections (complicated): 500 mg every 8 hours; diabetic foot: 1 g every 8 hours

Urinary tract infections, complicated (unlabeled use): 500 mg to 1 g every 8 hours

Dosing adjustment in renal impairment: Adults:

Cl_cr 26-50 mL/minute: Administer recommended dose based on indication every 12 hours

Cl_cr 10-25 mL/minute: Administer one-half recommended dose based on indication every 12 hours

Cl_cr <10 mL/minute: Administer one-half recommended dose based on indication every 24 hours

Intermittent hemodialysis: Meropenem and its metabolite are readily dialyzable; administer dose after dialysis session

Continuous renal replacement therapy (CRRT): 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 levels in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 L/hour) and should not supersede clinical judgment:

CVVH or CVVHD/CVVHDF: 1 g every 12 hours achieves target trough of ~4 mg/L; 500 mg every 12 hours may be considered for highly sensitive organisms. Note: Substantial variability exists in various published recommendations, ranging from 1-3 g/day given in 2-3 divided doses.

Administration: I.V.

Administer I.V. infusion over 15-30 minutes; I.V. bolus injection over 3-5 minutes.

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.

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) (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.

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.

Fish DN and Singletary TJ, “Meropenem, A New Carbapenem Antibiotic,” Pharmacotherapy, 1997, 17(4):644-69.

Hellinger WC and Brewer NS, “Carbapenems and Monobactams: Imipenem, Meropenem, and Aztreonam,” Mayo Clin Proc, 1999, 74(4):420-34.

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.

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

• Enem (TH)
• Eradix (ID)
• Lanmer (ID)
• Mapenem (TH)
• Meflupin (TW)
• Melopen (TW)
• Mepem (CL, TW)
• Merix (PH)
• Mero (TH)
• Merofen (ID)
• Meromax (PH)
• Meronem (BB, BE, BF, BG, BJ, BM, BR, BS, BZ, CH, CI, CN, CO, CR, CZ, DE, DK, DO, EC, EE, ES, ET, FI, GB, GH, GM, GN, GR, GT, GY, HK, HN, HU, ID, IE, IL, IN, JM, KE, LR, LU, MA, ML, MR, MU, MW, MY, NE, NG, NI, NL, NO, PA, PE, PH, PK, PL, PT, RU, SC, SD, SE, SG, SL, SN, SR, SV, TH, TN, TR, TT, TZ, UG, UY, VE, ZA, ZM, ZW)
• Meropen (JP, KP, PH)
• Merosan (ID)
• Merozen (PY)
• Merrem (AU, IT, MX)
• Monem (TH)
• Myron (TW)
• Optinem (AT)
• Romenem (TH)
• Ronem (ID)
• Ropen (PH)
• Tripenem (ID)
• Zaxter (TH)
• Zeropenem (AR)

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Last full review/revision March 2011

Content last modified March 2011