MERREM IV
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MERREM IV (MERREM IV).
Meropenem is a carbapenem antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to cell death.
| Metabolism | Meropenem is primarily metabolized by hydrolysis of the beta-lactam ring, forming an inactive metabolite. Hepatic metabolism is minimal; renal excretion is the main route. |
| Excretion | Primarily renal (approximately 70% as unchanged drug) via glomerular filtration and tubular secretion; biliary/fecal excretion accounts for ~20% as microbiologically inactive metabolite; minimal nonrenal clearance. |
| Half-life | Terminal elimination half-life approximately 1 hour in adults with normal renal function; prolonged to 4–6 hours in moderate renal impairment and up to 10 hours in severe impairment; clinical context: dosing interval adjustment required for CrCl <50 mL/min. |
| Protein binding | Protein binding: approximately 2% (low); primarily bound to albumin; negligible displacement interactions. |
| Volume of Distribution | Volume of distribution (Vd): approximately 0.25 L/kg (range 0.2–0.3 L/kg); indicates distribution primarily into extracellular fluid; increased Vd in sepsis or critically ill patients may necessitate higher loading doses. |
| Bioavailability | Intravenous administration only; bioavailability 100% by IV route; no oral formulation; meropenem is not absorbed orally. |
| Onset of Action | Intravenous administration: rapid bactericidal activity within 30 minutes post-infusion; peak concentrations achieved at end of infusion; time to clinical response depends on indication and pathogen. |
| Duration of Action | Duration of antimicrobial effect approximately 8 hours for susceptible organisms; post-antibiotic effect (PAE) of 0.5–4 hours against Gram-negative bacilli; clinical note: maintain trough levels above MIC for beta-lactam antibiotics. |
1 g intravenously every 8 hours over 15-30 minutes for complicated intra-abdominal infections; 500 mg intravenously every 8 hours for complicated skin and skin structure infections.
| Dosage form | INJECTABLE |
| Renal impairment | For CrCl 26-50 mL/min: 500 mg IV every 8 hours; CrCl 10-25 mL/min: 500 mg IV every 12 hours; CrCl <10 mL/min: 500 mg IV every 24 hours. |
| Liver impairment | No dose adjustment required for hepatic impairment; pharmacokinetics not significantly altered in Child-Pugh classes A, B, or C. |
| Pediatric use | Infants and children (3 months to 12 years): 20 mg/kg IV every 8 hours (maximum 1 g per dose) for complicated skin infections; 20 mg/kg IV every 8 hours (max 1 g) for complicated intra-abdominal infections. |
| Geriatric use | No specific geriatric dose adjustment; dosing based on renal function; consider age-related decline in CrCl. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MERREM IV (MERREM IV).
| Breastfeeding | Meropenem is excreted in human milk in low concentrations; the milk-to-plasma (M/P) ratio is approximately 0.09. Due to low oral bioavailability in infants, systemic effects are unlikely. However, caution is recommended, and the drug should be used only if clearly needed. Alternative agents with more safety data may be preferred. |
| Teratogenic Risk | Meropenem (MERREM IV) is classified as FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, but no adequate and well-controlled studies in pregnant women exist. In the first trimester, the drug should be used only if clearly needed. In the second and third trimesters, no specific teratogenic effects have been reported, but caution is advised. Crosses the placenta with fetal serum concentrations approximately 50% of maternal levels. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to meropenem or other carbapenems","Severe hypersensitivity to beta-lactam antibacterials (e.g., penicillins, cephalosporins)"]
| Precautions | ["Hypersensitivity reactions (including anaphylaxis)","Seizures and other CNS adverse events (especially in patients with renal impairment or CNS disorders)","Clostridioides difficile-associated diarrhea (CDAD)","Reduced efficacy against MRSA and some ESBL-producing organisms","Renal impairment requires dose adjustment","Potential for superinfection"] |
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| Fetal Monitoring | Monitor maternal renal function (serum creatinine, BUN) and hepatic function (AST, ALT) at baseline and periodically during therapy. Observe for signs of hypersensitivity, diarrhea (Clostridioides difficile infection), and neurological symptoms (e.g., seizures). Fetal monitoring per standard obstetric practice is recommended; no specific fetal monitoring required. |
| Fertility Effects | In animal studies, meropenem did not impair fertility or reproductive performance at doses up to 1000 mg/kg/day. No human data on fertility effects exist; however, based on the mechanism of action (bacterial cell wall synthesis inhibition), direct effects on human fertility are unlikely. |