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. |
| Molecular Weight | 365.39 |
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 | There is no adequate data on use in pregnant women. Animal studies have not revealed evidence of teratogenicity. However, use only if clearly needed and benefit outweighs risk. |
| 2nd trimester | No known risk. Use with caution if benefit outweighs potential unknown risks. |
| 3rd trimester | No known risk. Use with caution., especially near term due to potential effects on fetal bone development (tetracycline class effects). |
Clinical note
Comprehensive clinical and safety monograph for KAFOCIN (KAFOCIN).
| Placental transfer | Cephaloglycin crosses the placenta. Fetal serum concentrations are approximately 10-30% of maternal serum levels. |
| Breastfeeding | Kafocin (cephaloglycin) is excreted into breast milk in low concentrations. However, potential for serious adverse reactions in nursing infants exists. Consider temporary cessation of breastfeeding or alternate therapy. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to cephaloglycin or any cephalosporinHistory of immediate hypersensitivity reaction to penicillins (cross-reactivity possible)
| 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 |
| Food/Dietary | No significant food interactions. Avoid alcohol during therapy and for 72 hours after completion to prevent disulfiram-like reaction (nausea, vomiting, headache). |
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| Lactation Rating | L3 (Moderately Safe) - Limited data suggests low risk, but caution advised. |
| 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. |
| 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. |
| Clinical Pearls |
| KAFOCIN (cefotaxime) is a third-generation cephalosporin with broad-spectrum activity against gram-negative bacteria including Enterobacteriaceae and Neisseria species. It penetrates cerebrospinal fluid well, making it effective for meningitis. Note that it has no activity against Enterococcus or Pseudomonas aeruginosa. Ensure renal dose adjustment for creatinine clearance below 20 mL/min. Administer IV or IM; avoid mixing with aminoglycosides in the same IV line due to physical incompatibility. |
| Patient Advice | Take exactly as prescribed; complete the full course even if you feel better. · Report any signs of allergic reaction: rash, itching, swelling, or difficulty breathing. · May cause diarrhea; if severe or bloody, contact your doctor immediately. · Avoid alcohol during treatment and for 72 hours after the last dose to prevent disulfiram-like reaction. · Do not take antacids or iron supplements within 2 hours of this medication. |