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 |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZEFAZONE (ZEFAZONE).
| Breastfeeding | Unknown if excreted in human breast milk. M/P ratio not established. Caution advised, weigh benefits against potential risk to infant. |
| 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 |
■ FDA Black Box Warning
There is no FDA black box warning for ZEFAZONE.
| Serious Effects |
["Known hypersensitivity to cephalosporins or any component of the formulation","Previous immediate hypersensitivity reaction to penicillins"]
| 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"] |
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| 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. |