PRIMAXIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PRIMAXIN (PRIMAXIN).
Imipenem inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to cell death. Cilastatin prevents renal metabolism of imipenem by inhibiting dehydropeptidase I.
| Metabolism | Imipenem is metabolized by renal dehydropeptidase I; cilastatin inhibits this enzyme, increasing imipenem half-life. |
| Excretion | Renal (approximately 70% as unchanged drug via glomerular filtration and tubular secretion) and 20-30% biliary/fecal. |
| Half-life | Terminal elimination half-life: 1 hour. In patients with impaired renal function, half-life extends up to 4-6 hours in moderate impairment and >10 hours in severe impairment. |
| Protein binding | 20% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | 0.30 L/kg. Indicates distribution into extracellular fluid; does not penetrate CSF significantly unless meninges inflamed. |
| Bioavailability | Intravenous: 100%. Intramuscular: approximately 60-75% with rapid absorption. |
| Onset of Action | Intravenous infusion: immediate (within minutes). Intramuscular injection: 30-60 minutes. |
| Duration of Action | 6-8 hours for susceptible organisms. May require dose adjustment for prolonged therapy in infections with higher MICs. |
1 g (imipenem 500 mg + cilastatin 500 mg) IV every 6 hours for adults with normal renal function. Maximum 4 g/day.
| Dosage form | POWDER |
| Renal impairment | CrCl 60-89 mL/min: 500 mg IV every 6 hours. CrCl 30-59 mL/min: 500 mg IV every 8 hours. CrCl 15-29 mL/min: 500 mg IV every 12 hours. CrCl <15 mL/min: Not recommended unless on hemodialysis. |
| Liver impairment | No specific Child-Pugh based adjustments required, as imipenem is minimally hepatically metabolized. |
| Pediatric use | Age ≥3 months: 15-25 mg/kg/dose IV every 6 hours (based on imipenem component). Maximum 2 g/day for children <40 kg; 4 g/day if ≥40 kg. |
| Geriatric use | No specific geriatric adjustments beyond renal function monitoring; dosing per renal adjustment based on estimated CrCl. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PRIMAXIN (PRIMAXIN).
| Breastfeeding | Imipenem is excreted in human milk; M/P ratio not reported. Cilastatin is not excreted. Caution advised; discontinue nursing or drug. |
| Teratogenic Risk | Teratogenicity not observed in animal studies; no adequate human studies in pregnant women. Use only if potential benefit justifies risk. Risk cannot be ruled out. |
| Fetal Monitoring | Monitor renal function, complete blood count, hepatic function, and signs of superinfection. Monitor for seizures, especially in patients with CNS disorders or renal impairment. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to any component (imipenem, cilastatin, or other carbapenems)","Hypersensitivity to beta-lactam antibiotics (severe reactions)","Severe renal impairment (CrCl ≤15 mL/min) not on hemodialysis","Concomitant use with valproic acid or divalproex sodium (risk of decreased valproic acid levels and seizures)"]
| Precautions | ["Seizures and CNS adverse events, especially with high doses or renal impairment","Clostridioides difficile-associated diarrhea","Hypersensitivity reactions including anaphylaxis","Pseudomembranous colitis","Overgrowth of nonsusceptible organisms","Potential for neuromuscular blockade"] |
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| Fertility Effects | No adverse effects on fertility observed in animal studies. Human data not available. |