IMIPENEM AND CILASTATIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IMIPENEM AND CILASTATIN (IMIPENEM AND CILASTATIN).
Imipenem inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to cell lysis. Cilastatin inhibits dehydropeptidase I, preventing renal metabolism of imipenem and increasing its urinary concentration.
| Metabolism | Imipenem is metabolized by dehydropeptidase I in the renal tubules; cilastatin inhibits this enzyme. Neither is significantly metabolized by the liver. |
| Excretion | Renal: ~70% (imipenem) and ~70-80% (cilastatin) excreted unchanged in urine via glomerular filtration and tubular secretion; biliary/fecal: ~20-30% (imipenem) as metabolites and unchanged drug; negligible fecal excretion of cilastatin. |
| Half-life | Imipenem: ~1 hour (normal renal function), prolonged to 2.5-4 hours in severe renal impairment (CrCl <20 mL/min); cilastatin: ~0.8-1 hour (normal renal function), prolonged similarly. Clinical context: half-life dictates dosing interval (e.g., q6-8h in normal renal function, q12h or longer in renal impairment). |
| Protein binding | Imipenem: ~20% bound to plasma proteins; cilastatin: ~40% bound. |
| Volume of Distribution | 0.2-0.4 L/kg (imipenem), suggesting distribution primarily into extracellular fluid; clinically, Vd is similar to total body water and increases in edema or ascites. |
| Bioavailability | IM: ~60-75% (bioavailability of imipenem); IV: 100% (complete). |
| Onset of Action | IV infusion: immediate (within 30-60 minutes) for therapeutic plasma concentrations; IM: peak serum levels at 1-2 hours post-dose. |
| Duration of Action | Approximately 6-8 hours with normal renal function, depending on dose and pathogen susceptibility; duration may be prolonged in renal impairment. Clinical note: bactericidal activity persists as long as serum concentrations exceed MIC. |
| Molecular Weight | 317.4 |
500 mg IV every 6 hours or 1000 mg IV every 8 hours; infusion over 30 minutes.
| Dosage form | POWDER |
| Renal impairment | CrCl 20-50 mL/min: 500 mg IV every 8 hours or 250 mg IV every 6 hours; CrCl <20 mL/min: 500 mg IV every 12 hours or 250 mg IV every 12 hours. |
| Liver impairment | No dose adjustment required for hepatic impairment. |
| Pediatric use | Neonates (≤7 days): 25 mg/kg IV every 12 hours; Infants (8 days - 3 months): 25 mg/kg IV every 8 hours; Children (≥3 months): 15-25 mg/kg IV every 6 hours (max 2 g/day). |
| Geriatric use | Use with caution; adjust dose based on renal function; monitor for seizure risk due to age-related decreased renal function. |
| 1st trimester | Human data limited; animal studies show no evidence of teratogenicity; use only if clearly needed. |
| 2nd trimester | Considered safe; crosses placenta; no known harm. |
| 3rd trimester | Considered safe; monitor for potential neonatal effects if used near term. |
Clinical note
Comprehensive clinical and safety monograph for IMIPENEM AND CILASTATIN (IMIPENEM AND CILASTATIN).
| Placental transfer | Crosses the placenta; achieves therapeutic concentrations in fetal tissues. |
| Breastfeeding | Excreted into breast milk in low concentrations; unlikely to cause adverse effects in infants; compatible with breastfeeding. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to imipenem, cilastatin, or any carbapenemHypersensitivity to other beta-lactam antibiotics (e.g., penicillins, cephalosporins)
| Precautions | Seizures, especially in patients with CNS disorders, renal impairment, or exceeding recommended doses, Pseudomembranous colitis due to Clostridium difficile, Hypersensitivity reactions, including anaphylaxis, Renal impairment requires dose adjustment, Overgrowth of nonsusceptible organisms |
| Food/Dietary | No specific food restrictions. Administer intravenously; absorption is not affected by food. Avoid alcohol due to potential for disulfiram-like reaction (though rare with this drug). |
Loading safety data…
| L2 (Probably Compatible) |
| Teratogenic Risk | Human data: limited. Animal studies: no evidence of teratogenicity at clinically relevant doses. FDA Pregnancy Category C. First trimester: theoretical risk based on animal data, but human data insufficient. Second and third trimesters: no documented fetal harm, but caution advised due to potential alteration of maternal gut flora and risk of neonatal diarrhea. Overall: low teratogenic potential; use only if clearly needed. |
| Fetal Monitoring | Monitor maternal renal function and signs of superinfection (oral/vaginal candidiasis, diarrhea). Assess for signs of hypersensitivity. In pregnancy, monitor for preterm labor due to possible gastrointestinal disturbance. Fetal monitoring not specific; standard obstetric surveillance. |
| Fertility Effects | No human data on fertility impairment; animal studies showed no adverse effects on mating or fertility at doses up to 2.6 mg/kg. No evidence of impact on spermatogenesis or ovulation. |
| Clinical Pearls |
| Imipenem has a high propensity for seizure induction, especially with renal impairment (CrCl <5 mL/min) or CNS disorders. Cilastatin inhibits renal dehydropeptidase I to prevent imipenem metabolism. Dose adjustment based on renal function is critical. Monitor for Clostridioides difficile infection. Avoid in patients with known hypersensitivity to carbapenems or beta-lactams. |
| Patient Advice | Take this medication exactly as prescribed, usually every 6-8 hours. · Complete the full course even if you feel better, to prevent resistance. · Report any signs of allergic reaction (rash, itching, difficulty breathing) immediately. · Inform your doctor if you have a history of seizures, kidney problems, or colitis. · This drug may cause diarrhea; notify your doctor if severe or persistent. · Do not mix with alcohol as it may increase side effects. |