meropenem
Merrem IV

Available forms
Available by prescription only
Powder for injection: 500 mg/15 ml, 500 mg/20 ml, 500 mg/100 ml, 1 g/15 ml, 1 g/30 ml, 1 g/100 ml

Indications and dosages
 Complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus sp.; bacterial meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. Recommended concentration not to exceed 50 mg/ml. Adults: Give 1 g I.V. q 8 hours over 15 to 30 minutes as I.V. infusion or over about 3 to 5 minutes as I.V. bolus injection (5 to 20 ml).
Children age 3 months and older who weigh 50 kg (110 lb) or less: 20 mg/kg (intra-abdominal infection) or 40 mg/kg (bacterial meningitis) q 8 hours over 15 to 30 minutes as I.V. infusion or over about 3 to 5 minutes as I.V. bolus injection (5 to 20 ml).
Children who weigh more than 50 kg: 1 g q 8 hours for intra-abdominal infections and 2 g q 8 hours for meningitis.
≡ Dosage adjustment. For adults with renal impairment, give 1 g q 12 hours if creatinine clearance is 26 to 50 ml/minute, 500 mg q 12 hours if it’s 10 to 25 ml/minute, and 500 mg q 24 hours if it’s less than 10 ml/minute. There’s no clinical experience in children with renal impairment.

Pharmacodynamics
Antibiotic action: Meropenem inhibits cell wall synthesis in bacteria. It readily penetrates the cell wall of most gram-positive and gram-negative bacteria to reach penicillin-binding protein targets.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: Distributed into most body fluids and tissues, including CSF. It’s only about 2% bound to plasma protein.
Metabolism: Thought to undergo minimal metabolism. One inactive metabolite has been identified.
Excretion: Excreted unchanged primarily in urine. Elimination half-life of drug in adults with normal renal function and children age 2 and older is about 1 hour and 1 1/2 hours in children age 3 months to 2 years.

Contraindications and precautions
Contraindicated in patients hypersensitive to components of drug or other drugs in the same class and in those who have demonstrated anaphylactoid reactions to beta-lactams. Use cautiously in patients with history of seizure disorders or impaired renal function.

Interactions
Drug-drug. Probenecid: Competes with meropenem for active tubular secretion and thus inhibits the renal excretion of meropenem. Avoid use together.

Adverse reactions
CNS: headache, syncope, insomnia, agitation, delirium, confusion, fever, dizziness, pain, seizures, nervousness, paresthesia, hallucinations, somnolence, anxiety, depression.
CV: heart failure, cardiac arrest, MI, pulmonary embolism, tachycardia, chest pain, hypertension, bradycardia, hypotension.
GI: diarrhea, nausea, vomiting, constipation, abdominal pain or enlargement, oral candidiasis, anorexia.
GU: dysuria, kidney failure.
Hematologic: bleeding events, anemia.
Hepatic: hepatic failure, cholestatic jaundice, jaundice, flatulence, ileus.
Musculoskeletal: back pain.
Respiratory: apnea, hypoxia, respiratory disorder, dyspnea.
Skin: rash; pruritus; urticaria; sweating; inflammation; pain, edema, phlebitis, or thrombophlebitis at injection site.
Other: hypersensitivity reactions, anaphylaxis, sepsis, shock, peripheral edema.

Effects on lab test results
• May increase ALT, AST, bilirubin, alkaline phosphatase, LDH, creatinine, and BUN levels.
• May increase eosinophil and RBC counts in urine. May decrease hemoglobin, hematocrit, and WBC count. May increase or decrease platelet count, PT, INR, and PTT.

Overdose and treatment
Signs and symptoms of overdose are unknown.
 If overdose occurs, discontinue drug and give general supportive treatment until renal elimination occurs. Meropenem and its metabolite are readily removed by hemodialysis.

Special considerations
• Don’t use drug to treat methicillin-resistant staphylococci.
• Obtain specimen for culture and sensitivity tests before giving first dose. Therapy may begin pending test results.
• Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients receiving therapy with beta-lactams. Before therapy starts, ascertain whether previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams, and other allergens have occurred.
• Discontinue drug immediately if an allergic reaction occurs. Serious anaphylactoid reactions require immediate emergency treatment with epinephrine, oxygen, I.V. corticosteroids, and airway management. Other therapy may also be required as indicated by the patient’s condition.
• Seizures and other CNS adverse reactions caused by meropenem therapy commonly occur in patients with CNS disorders, bacterial meningitis, and compromised renal function.
• If seizures occur during meropenem therapy, decrease dosage or discontinue meropenem.
• For I.V. bolus, add 10 ml of sterile water for injection to 500 mg/20 ml vial size or 20 ml to 1 g/30 ml vial size to provide 50 mg/ml. Shake to dissolve and let stand until clear.
• For I.V. infusion, infusion vials (500 mg/100 ml and 1 g/100 ml) may be directly reconstituted with a compatible infusion fluid to provide 2.5 to 50 mg/ml. Or, an injection vial may be reconstituted and the resulting solution added to an I.V. container and further diluted with an appropriate infusion fluid. ADD-Vantage vials shouldn’t be used.
• For ADD-Vantage vials, reconstitute only with half-normal saline solution injection, normal saline solution injection, or D₅W injection in 50-, 100-, or 250-ml Abbott ADD-Vantage flexible diluent containers. Follow manufacturer guidelines closely when using ADD-Vantage vials.
• Don’t mix with or physically add meropenem to solutions containing other drugs. Infuse drug over 15 to 30 minutes.
• Use freshly prepared solutions of meropenem immediately whenever possible. Stability of drug varies with type of drug used (injection vial, infusion vial, or ADD-Vantage container). Consult manufacturer’s literature for details.
• Drug may cause overgrowth of nonsusceptible bacteria or fungi. Monitor patient for signs and symptoms of superinfection.
• Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety and efficacy haven’t been established in children younger than age 3 months.
Geriatric patients
• Use cautiously in geriatric patients because of decreased renal function. Dosage adjustment is recommended in patients of advanced age whose creatinine clearance levels are less than 50 ml/minute.

Patient education
• Tell patient to report pain, inflammation, or swelling at I.V. site.
• Advise breast-feeding patient of risk of transmitting drug to infant through breast milk.
• Instruct patient to report adverse reactions or symptoms of superinfection.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use