ZEFAZONE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZEFAZONE (ZEFAZONE).
ZEFAZONE is a cephalosporin antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs).
| Metabolism | ZEFAZONE is not significantly metabolized; it is primarily excreted unchanged by the kidneys. |
| Excretion | Primarily renal (80-90% unchanged via glomerular filtration and tubular secretion); minor biliary excretion (10-20%) |
| Half-life | 1.5-2 hours in normal renal function; prolonged to 20-30 hours in severe renal impairment (CrCl <10 mL/min), necessitating dose adjustment |
| Protein binding | 85-90% primarily to albumin; saturable at high concentrations |
| Volume of Distribution | 0.2-0.3 L/kg; indicates distribution primarily into extracellular fluid and tissues (low Vd), with minimal CNS penetration except inflamed meninges |
| Bioavailability | IM: >95%; oral not available (not formulated) |
| Onset of Action | IM: ~30 minutes; IV: immediate (~1-2 min); oral: 1-2 hours |
| Duration of Action | 6-8 hours for susceptible organisms; extended to 12 hours with probenecid coadministration |
| Molecular Weight | 512.34 |
1 g IV/IM every 8 hours for moderate to severe infections; 2 g IV/IM every 8 hours for life-threatening infections.
| Dosage form | INJECTABLE |
| Renal impairment | GFR >50 mL/min: no adjustment; GFR 10-50 mL/min: 1 g every 12 hours; GFR <10 mL/min: 1 g every 24 hours. |
| Liver impairment | No adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Child-Pugh C: reduce dose by 50% and monitor closely. |
| Pediatric use | 50 mg/kg/day IV/IM divided every 8 hours for mild to moderate infections; 100 mg/kg/day divided every 6 hours for severe infections. Maximum 6 g/day. |
| Geriatric use | No specific dose adjustment based on age alone; adjust based on renal function (see renal adjustment). Monitor for renal function and potential neurotoxicity. |
| 1st trimester | Avoid; associated with fetal abnormalities in animal studies; insufficient human data. |
| 2nd trimester | Limited safety data; use only if potential benefit outweighs risk. |
| 3rd trimester | Avoid; potential for fetal toxicity and neonatal complications. |
Clinical note
Comprehensive clinical and safety monograph for ZEFAZONE (ZEFAZONE).
| Placental transfer | Crosses placenta in animal models; human data limited but suggests transfer. |
| Breastfeeding | Excreted in breast milk in low amounts; monitor infant for diarrhea and rash. Use with caution. |
| Lactation Rating | L3 |
■ FDA Black Box Warning
There is no FDA black box warning for ZEFAZONE.
| Serious Effects |
Hypersensitivity to zefazone or other cephalosporinsSevere renal impairment (CrCl <10 mL/min)
| Precautions | Hypersensitivity reactions including anaphylaxis, Clostridium difficile-associated diarrhea (CDAD), Potential for nephrotoxicity when used with aminoglycosides, Use with caution in patients with renal impairment, Use with caution in patients with a history of penicillin allergy |
| Food/Dietary | Administer with food or on an empty stomach. No specific food interactions known. Avoid alcohol during therapy due to potential disulfiram-like reaction (ethanol intolerance). |
Loading safety data…
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. Animal studies have not demonstrated teratogenic effects. Risk cannot be ruled out. Considered Pregnancy Category B. First trimester: no known association with major malformations. Second and third trimesters: no known adverse fetal effects. |
| Fetal Monitoring | Monitor for maternal allergic reactions, superinfection, diarrhea. Fetal monitoring not specifically required; standard prenatal care. |
| Fertility Effects | No known effects on fertility in animal studies. Human data lacking. |
| Clinical Pearls |
| ZEFAZONE (cefazoline) is a first-generation cephalosporin with activity against Gram-positive cocci (except MRSA) and some Gram-negatives. Adjust dose in renal impairment (CrCl <30 mL/min: give q12h instead of q8h). Can cause positive Coombs test without hemolysis. Avoid in penicillin-allergic patients (cross-reactivity ~10%). Administer IV/IM deep IM; IV push over 3-5 min or infusion over 30 min. Monitor renal function and CBC during prolonged therapy. |
| Patient Advice | Take this antibiotic exactly as prescribed, even if you feel better. · Notify your doctor if you have a history of severe allergic reaction to penicillins or cephalosporins. · Common side effects include diarrhea, nausea, and injection site pain. Report severe diarrhea or rash. · Avoid alcohol during treatment and for 72 hours after the last dose (disulfiram-like reaction possible). · If you develop unusual bleeding or bruising, contact your healthcare provider. |