meropenem (Rx)

1-10%

Constipation (1-7%)

Diarrhea (4-5%)

Nausea or vomiting (1-4%)

Rash (2-3%; includes diaper-area moniliasis in pediatric patients)

Headache (2%)

Inflammation at injection site (2%)

Sepsis (2%)

Oral moniliasis (≤2% in pediatric patients)

Bleeding (1.2%)

Apnea (1%)

Constipation (1%)

Glossitis (1%)

Injection-site reaction (1%)

Phlebitis or thrombophlebitis (1%)

Pruritus (1%)

Septic shock (1%)

<1%

Agranulocytosis

Angioedema

Erythema multiforme

Hypersensitivity reaction

Hypokalemia

Leukopenia

Neutropenia

Pleural effusion

Stevens-Johnson syndrome

Toxic epidermal necrolysis

Postmarketing Reports

Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme and acute generalized exanthematous pustulosis

Contraindications

Hypersensitivity to IV components, beta-lactams, or other drugs in this class

Cautions

Hypersensitivity reactions have been reported, including fatalities; these reactions are more likely to occur in individuals with history of sensitivity to multiple allergens

Seizures have been reported, most commonly in patients with CNS disorders (eg, brain lesions, history of seizures) or with bacterial meningitis or compromised renal function

Seizures, headaches, or paresthesias may occur, potentially interfering with mental alertness or causing motor impairment

Clostridium difficile-associated diarrhea has been reported

To avoid development of drug resistance, drug should be used only in proven or strongly suspected bacterial infections or a prophylactic indication

Prolonged use may result in overgrowth of nonsusceptible organisms

Thrombocytopenia has been reported in patients with renal impairment

Co-administration of meropenem IV with valproic acid or divalproex sodium reduces serum concentrations of valproic acid potentially increasing risk of breakthrough seizures

Severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme (EM) and acute generalized exanthematous pustulosis (AGEP) reported; if signs and symptoms suggestive of these reactions appear, therapy should be withdrawn immediately and an alternative treatment considered

Pregnancy

There are insufficient human data to establish whether there is a drug-associated risk of major birth defects or miscarriages with meropenem in pregnant women

Animal data

• No fetal toxicity or malformations were observed in pregnant rats and Cynomolgus monkeys administered intravenous meropenem during organogenesis at doses up to 2.4 and 2.3 times the maximum recommended human dose (MRHD) based on body surface area comparison, respectively; in rats administered intravenous meropenem in late pregnancy and during lactation period, there were no adverse effects on offspring at doses equivalent to approximately 3.2 times the MRHD based on body surface area comparison

Lactation

Drug has been reported to be excreted in human milk; no information is available on effects of drug on breast-fed child or on milk production; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breast-fed child from therapy or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Inhibits cell-wall synthesis by binding to penicillin-binding proteins; resistant to most beta-lactamases

Absorption

Peak tissue time: 1 hr after infusion

Distribution

Penetrates well into most body fluids and tissues; CSF concentrations approximate those in plasma

Protein bound: 2%

Vd: Adults, 15-20 L; children, 0.3-0.4 L/kg

Metabolism

Metabolized in liver to open beta-lactam form (inactive)

Elimination

Half-life: Normal renal function, 1-1.5 hr; CrCl >30-80 mL/min, 1.9-3.3 hr; CrCl >2-30 mL/min, 3.82-5.7 hr

Excretion: Urine (~25% as inactive metabolites)

IV Incompatibilities

Additive: Amphotericin B, metronidazole, multivitamins

Y-site: Amphotericin B, diazepam, metronidazole

IV Administration

Administer IV infusion over 15-30 minutes; administer IV bolus over 3-5 minutes

Storage

Store powder at controlled room temperature