KAFOCIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KAFOCIN (KAFOCIN).
KAFOCIN (cefepime/enmetazobactam) is a combination of a fourth-generation cephalosporin (cefepime) and a β-lactamase inhibitor (enmetazobactam). Enmetazobactam inhibits extended-spectrum β-lactamases (ESBLs) and other class A β-lactamases, restoring cefepime's activity against β-lactamase-producing bacteria. Cefepime inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to cell death.
| Metabolism | Cefepime undergoes minimal metabolism; enmetazobactam is primarily metabolized by hydrolysis to an inactive metabolite. Both are predominantly excreted renally as unchanged drug. |
| Excretion | Renal: 60-80% unchanged; biliary/fecal: 15-30% as metabolites; total clearance ~120 mL/min. |
| Half-life | Terminal elimination half-life: 4.5-6.5 hours (increased to 12-18 hours in severe renal impairment; CrCl <30 mL/min). |
| Protein binding | 75-85% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.3-0.4 L/kg; indicates distribution primarily into extracellular fluid; increases in sepsis (up to 0.6 L/kg). |
| Bioavailability | Oral: 35-50% (fasting), reduced by food; IM: 80-90%. |
| Onset of Action | IV: immediate; IM: 30-60 minutes; oral: 1-2 hours. |
| Duration of Action | 12-24 hours depending on dose and infection site; prolonged in renal impairment. |
1 g IV every 8 hours.
| Dosage form | CAPSULE |
| Renal impairment | CrCl 30-50 mL/min: 1 g IV every 12 hours; CrCl 10-29 mL/min: 1 g IV every 24 hours; CrCl <10 mL/min: 0.5 g IV every 24 hours. |
| Liver impairment | No dose adjustment required for Child-Pugh Class A or B; Child-Pugh Class C: use with caution, monitor liver function. |
| Pediatric use | Neonates: 20 mg/kg IV every 12 hours; Infants and children: 30 mg/kg IV every 8 hours; maximum 1 g per dose. |
| Geriatric use | No specific dose adjustment based solely on age; adjust dose based on renal function using creatinine clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KAFOCIN (KAFOCIN).
| Breastfeeding | Cefoperazone is excreted into human milk in low concentrations; sulbactam excretion is unknown. The M/P ratio for cefoperazone is approximately 0.01-0.05. Due to potential for disruption of infant gut flora and allergic sensitization, use during breastfeeding only if clearly needed. Monitor infant for diarrhea, rash, or yeast infections. |
| Teratogenic Risk | KAFOCIN (cefoperazone/sulbactam) is a Pregnancy Category B drug. Animal studies have not demonstrated fetal risk, but there are no adequate and well-controlled studies in pregnant women. First trimester: No known teratogenic effects, but caution is advised. Second and third trimesters: Use only if clearly needed; no reported fetal harm, but immature fetal hepatic function may be considered. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Known hypersensitivity to cefepime, enmetazobactam, or other β-lactams","History of severe hypersensitivity reaction to any cephalosporin"]
| Precautions | ["Hypersensitivity reactions, including anaphylaxis, in patients with penicillin or other β-lactam allergies","Clostridioides difficile-associated diarrhea (CDAD)","Neurotoxicity (e.g., encephalopathy, myoclonus, seizures) especially in renal impairment","Risk of bleeding in patients with renal impairment; monitor prothrombin time"] |
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| Fetal Monitoring | Monitor maternal renal and hepatic function during prolonged therapy. Assess for signs of hypersensitivity or superinfection. In neonates, monitor for bilirubin displacement due to cefoperazone's high protein binding; caution in jaundiced newborns. |
| Fertility Effects | No human studies on fertility effects. Animal studies with cefoperazone/sulbactam have not shown impaired fertility. No anticipated adverse effects on fertility based on mechanism. |