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. |
| Molecular Weight | 513.6 |
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 | Insufficient human data; animal studies show no teratogenicity. Use only if benefit outweighs risk. |
| 2nd trimester | No known harm; use with caution. |
| 3rd trimester | No known harm; use with caution. |
Clinical note
Comprehensive clinical and safety monograph for PRIMAXIN (PRIMAXIN).
| Placental transfer | Crosses placenta; fetal exposure is low to moderate. |
| Breastfeeding | Excreted in low levels; considered compatible with breastfeeding. |
| Lactation Rating | L2 |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to any componentHypersensitivity to other carbapenemsHypersensitivity to beta-lactamsHistory of anaphylactic reaction to penicillins or cephalosporins
| 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 |
| Food/Dietary | No significant food interactions. Grapefruit juice does not affect metabolism. Take with or without food. Maintain adequate hydration. |
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| 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. |
| Fertility Effects | No adverse effects on fertility observed in animal studies. Human data not available. |
| Clinical Pearls |
| Primaxin (imipenem/cilastatin) should be dosed based on renal function. It is contraindicated in patients with severe beta-lactam allergy. May cause seizures, especially in elderly or those with renal impairment. Not effective against MRSA or atypical pneumonias. Use with caution in patients with CNS disorders. |
| Patient Advice | Take this medication exactly as prescribed, even if you feel better. · Common side effects: nausea, vomiting, diarrhea, injection site reactions. · Report any signs of allergic reaction (rash, itching, difficulty breathing) immediately. · If you experience seizures, confusion, or muscle twitching, contact your doctor. · This drug may interact with valproic acid; do not take them together. · Notify your physician if you have kidney problems, as dose adjustment may be needed. |