Pronunciation: MER-oh-PEN-em
Class: Carbapenem antibiotic

Trade Names

Merrem I.V.
- Injection, powder for solution 500 mg
- Injection, powder for solution 1 g

Pharmacology

Inhibits bacterial cell wall synthesis.

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Pharmacokinetics

Absorption

T _max is approximately 1 h after start of infusion. Mean C _max for a 30-min infusion is 23 mcg/mL (500 mg dose) and 49 mcg/mL (1 g dose). Mean C _max for a 5-min bolus injection is 45 mcg/mL (500 mg dose) and 112 mcg/mL (1 g dose).

Distribution

Protein binding is approximately 2% and penetrates well into most body fluids and tissues, including CSF.

Metabolism

There is 1 metabolite that is inactive.

Elimination

Approximately 70% is excreted in urine unchanged over 12 h. Elimination half-life is approximately 1 h.

Special Populations

Renal Function Impairment

Cl correlates with CrCl in patients with renal function impairment. Dosage adjustments may be necessary.

Hepatic Function Impairment

Hepatic function impairment does not affect the pharmacokinetics.

Elderly

A reduction in plasma Cl correlates with age-associated reduction in CrCl.

Children

The half-life in children 3 mo to 2 y of age is approximately 1.5 h.

Indications and Usage

Single-agent treatment of complicated skin and skin structure infections, complicated intra-abdominal infections (ie, appendicitis, peritonitis), and bacterial meningitis when caused by susceptible microorganisms.

Unlabeled Uses

Empiric therapy in febrile neutropenic patients; community-acquired pneumonia (if Pseudomonas is a concern); hospital-acquired pneumonia (including ventilator-associated pneumonia and health care- associated pneumonia).

Contraindications

Hypersensitivity to any component of this product or to other drugs in the same class; anaphylactic reactions to beta-lactams.

Dosage and Administration

Intra-Abdominal Infections
Adults

IV 1 g every 8 h.

Children (3 mo and older) Weighing more than 50 kg

IV 1 g every 8 h.

Weighing 50 kg or less

IV 20 mg/kg every 8 h.

Max dose

IV 1 g every 8 h

Bacterial Meningitis
Children (3 mo and older) Weighing more than 50 kg

IV 2 g every 8 h.

Weighing 50 kg or less

IV 40 mg/kg every 8 h.

Max dose

IV 2 g every 8 h.

Complicated Skin and Skin Structure Infections
Adults

IV 500 mg every 8 h.

Children (3 mo and older) Weighing more than 50 kg

IV 500 mg every 8 h.

Weighing 50 kg or less

IV 10 mg/kg every 8 h.

Max dose

IV 500 mg every 8 h.

Renal Function Impairment
Adults CrCl greater than 25 to 50 mL/min

Recommended dose every 12 h.

CrCl 10 to 25 mL/min

50% of recommended dose every 12 h.

CrCl less than 10 mL/min

50% of recommended dose every 24 h.

Continuous renal replacement therapy

1 to 2 g every 12 h. Alternative recommendations assume ultrafiltration and dialysis flow rates of 1 to 2 L/h.

Loading dose

IV 1 g.

Maintenance dose Continuous venovenous hemofiltration

500 mg to 1 g IV every 12 h or 500 mg IV every 8 h.

Continuous venovenous hemodialysis or continuous venovenous hemodiafiltration

500 mg to 1 g IV every 8 to 12 h or 500 mg IV every 6 to 8 h.

Peritoneal Dialysis

100% of the recommended dose every 24 h.

Intermittent Hemodialysis

500 mg IV every 24 h after dialysis.

Off-Label Dosing
Community-Acquired Pneumonia Adults

Empirically, 500 mg every 8 h for a minimum of 5 days, used in combination with a fluoroquinolone.

Empiric Therapy in Febrile Neutropenic Patients Adults

IV 1 g every 8 h.

Hospital-Acquired Pneumonia Adults

IV 1 g every 8 h. Duration of treatment is 7 to 8 days for uncomplicated hospital-acquired pneumonia infections.

Neonates

IV 15 to 20 mg/kg every 12 h.

For neonates 7 days and older who weigh more than 2 kg, a dosage of IV 20 mg/kg every 8 h has been suggested. Administer dose over 15 to 30 min.

General Advice

• For IV bolus (doses of 1 g) or infusion only. Not for intradermal, subcutaneous, IM, or intra-arterial administration. Do not use a flexible container in series connections.
• Administer IV infusion over approximately 15 to 30 min. Administer IV bolus (5 to 20 mL) over approximately 3 to 5 min.
• Do not mix with or physically add to solutions containing other drugs.

Storage/Stability

Store dry powder between 68° and 77°F. Stability of reconstituted meropenem is dependent on diluent and container (eg, syringe, infusion vial, minibag). Refer to manufacturer's package insert for guidelines.

Drug Interactions

Probenecid

Inhibits renal excretion of meropenem. Coadministration is not recommended.

Valproic acid and derivatives

Meropenem may decrease valproic acid levels to subtherapeutic levels, resulting in a loss of seizure control. Monitor valproic acid plasma concentrations and observe the patient for seizure activity. Consider adjusting the valproic acid dose as needed or using an alternative antibiotic. If meropenem therapy is necessary, consider supplemental anticonvulsant therapy.

Adverse Reactions

Cardiovascular

Bradycardia, cardiac arrest, heart failure, hypertension, hypotension, MI, pulmonary embolus, syncope, tachycardia (1% or less).

CNS

Headache (8%); agitation/delirium, anxiety, asthenia, confusion, depression, dizziness, hallucinations, insomnia, nervousness, paresthesia, seizures, somnolence (1% or less).

Dermatologic

Diaper rash, rash (3%); pruritus (1%); skin ulcer, sweating, urticaria (1% or less); angioedema, erythema multiforme, Stevens-Johnson syndrome, TEN (postmarketing).

EENT

Pharyngitis (at least 1%).

GI

Nausea (8%); constipation, diarrhea (7%); vomiting (4%); oral moniliasis (2%); GI disorder (at least 1%); GI hemorrhage, glossitis (1%); abdominal pain/enlargement, anorexia, dyspepsia, flatulence, ileus, intestinal obstruction (1% or less).

Genitourinary

Dysuria, kidney failure, urinary incontinence, vaginal moniliasis (1% or less); presence of RBC in urine.

Hematologic-Lymphatic

Anemia (6%); hypochromic anemia (1% or less); agranulocytosis, hemolytic anemia, leukopenia, neutropenia, positive direct and indirect Coombs test (postmarketing).

Hepatic

Cholestatic jaundice, hepatic failure, jaundice (1% or less).

Lab Tests

Decreased Hct, Hgb, platelets, and WBC; increased alkaline phosphatase, ALT, AST, bilirubin, BUN, creatinine, eosinophils, LDH, and platelets; hypokalemia, leukocytosis, shortened PT/PTT.

Local

Inflammation at injection site (2%); injection-site reaction, phlebitis/thrombophlebitis (1%).

Metabolic-Nutritional

Hypoglycemia (at least 1%); hypovolemia, hypoxia, peripheral edema (1% or less).

Respiratory

Pneumonia (at least 1%); apnea (1%); asthma, cough increased, dyspnea, lung edema, pleural effusion, respiratory disorder (1% or less).

Miscellaneous

Pain (5%); sepsis (2%); peripheral vascular disorder (at least 1%); shock (1%); back pain, chest pain, chills, fever, pelvic pain (1% or less).

Precautions

Monitor Monitor patient's response to therapy; periodically monitor renal, hepatic, and hematopoietic function during prolonged therapy.

Pregnancy

Category B . Placental transfer to the fetus may occur.

Lactation

Undetermined. Excretion into breast milk may occur.

Children

Safety and efficacy in children 3 mo and younger not established.

Elderly

Use care in dose selection because elderly patients are more likely to have decreased renal function; monitor renal function.

Hypersensitivity

Serious and occasionally fatal anaphylactic reactions have been reported with beta-lactam therapy. Patients with sensitivity to multiple allergens are at greatest risk. Use with caution in penicillin-sensitive patients.

Renal Function

Adjust dose downward accordingly in patients with CrCl of 50 mL/min or less. Thrombocytopenia without bleeding has been observed.

Superinfection

May result in bacterial or fungal overgrowth of nonsusceptible organisms.

CNS effects

Seizures and other CNS adverse reactions have been reported. Use with caution in patients with CNS disorders, meningitis, or renal function impairment.

Clostridium difficile – associated diarrhea

Consider possibility in patients with diarrhea.

Patient Information

• Advise patient, family, or caregiver to immediately report any of the following to health care provider: black, furry tongue; difficulty breathing or unexplained shortness of breath; foul-smelling, watery, or bloody stools; hives; rash; vaginal itching or discharge; white patches in mouth.
• Warn patient, family, or caregiver that if diarrhea containing blood or pus develops after discharge, it may be a sign of a serious disorder. Instruct patient to seek medical care if noted and not to treat at home.
• Advise patient to inform health care provider if they are taking valproic acid or divalproex sodium for seizures. Therapy modifications may be needed.

Copyright © 2009 Wolters Kluwer Health.