Cefepime

Parenteral
Skin and skin structure infections
Adult: Dose and route of administration may vary according to the severity of the infection, renal function and general condition of the patient. Mild to moderate cases: 1 g 12 hourly via IV inj or infusion over at least 30 minutes or IM inj. Severe cases: 2 g 12 hourly via IV inj or infusion over at least 30 minutes, may be increased to 2 g 8 hourly for very severe infections. Max: 2 g 8 hourly. Usual treatment duration: 7-10 days. Dosage recommendations may vary among countries and individual products (refer to detailed product or local treatment guidelines).
Child: >2 months ≤40 kg: 50 mg/kg 12 hourly for 10 days, may increase frequency to 8 hourly in more severe cases; >40 kg: Same as adult dose. Dosage recommendations may vary among countries and individual products (refer to detailed product or local treatment guidelines).
Renal impairment: Patients undergoing haemodialysis: 1 g as loading dose on the 1st day, followed by 0.5 g 24 hourly; administer after dialysis during dialysis days. In patients with mild to moderate renal insufficiency, initial dose recommended is similar in patients with normal renal function.

CrCl (ml/min)	Dosage Recommendation
<11	Maintenance: 0.25-1 g 24 hourly.
11-29	Maintenance: 0.5-2 g 24 hourly.
30-60	Maintenance: 0.5-2 g 24 hourly or 2 g 12 hourly.

Reconstitution: IV: Reconstitute vials labelled as 500 mg with 5 mL and 1 g or 2 g with 10 mL of compatible IV diluent to yield a final concentration of 100 mg/mL (500 mg and 1 g vial) or 160 mg/mL (2 g vial). May further dilute in a compatible IV infusion fluid. IM: Reconstitute vials labelled as 500 mg or 1 g with 1.3 mL or 2.4 mL, respectively, of sterile water for inj, NaCl 0.9%, dextrose 5% in water, lidocaine 0.5% or 1%, or bacteriostatic water for inj to a yield a final concentration of 280 mg/mL.
Incompatibility: Incompatible with metronidazole, aminophylline, gentamicin, tobramycin, netilmicin, vancomycin, and ampicillin (at a concentration >40 mg/mL).

Parenteral
Lower respiratory tract infections
Adult: Dose and route of administration may vary according to the severity of the infection, renal function and general condition of the patient. Mild to moderate cases: 1 g 12 hourly via IV inj or infusion over at least 30 minutes or IM inj. Severe cases: 2 g 12 hourly via IV inj or infusion over at least 30 minutes, may be increased to 2 g 8 hourly for very severe infections. Max: 2 g 8 hourly. Usual treatment duration: 7-10 days. Dosage recommendations may vary among countries and individual products (refer to detailed product or local treatment guidelines).
Child: >2 months ≤40 kg: 50 mg/kg 12 hourly for 10 days, may increase frequency to 8 hourly in more severe cases; >40 kg: Same as adult dose. Dosage recommendations may vary among countries and individual products (refer to detailed product or local treatment guidelines).
Renal impairment: Patients undergoing haemodialysis: 1 g as loading dose on the 1st day, followed by 0.5 g 24 hourly; administer after dialysis during dialysis days. In patients with mild to moderate renal insufficiency, initial dose recommended is similar in patients with normal renal function.

CrCl (ml/min)	Dosage Recommendation
<11	Maintenance: 0.25-1 g 24 hourly.
11-29	Maintenance: 0.5-2 g 24 hourly.
30-60	Maintenance: 0.5-2 g 24 hourly or 2 g 12 hourly.

Reconstitution: IV: Reconstitute vials labelled as 500 mg with 5 mL and 1 g or 2 g with 10 mL of compatible IV diluent to yield a final concentration of 100 mg/mL (500 mg and 1 g vial) or 160 mg/mL (2 g vial). May further dilute in a compatible IV infusion fluid. IM: Reconstitute vials labelled as 500 mg or 1 g with 1.3 mL or 2.4 mL, respectively, of sterile water for inj, NaCl 0.9%, dextrose 5% in water, lidocaine 0.5% or 1%, or bacteriostatic water for inj to a yield a final concentration of 280 mg/mL.
Incompatibility: Incompatible with metronidazole, aminophylline, gentamicin, tobramycin, netilmicin, vancomycin, and ampicillin (at a concentration >40 mg/mL).

Parenteral
Intra-abdominal infections
Adult: Dose and route of administration may vary according to the severity of the infection, renal function and general condition of the patient. Mild to moderate cases: 1 g 12 hourly via IV inj or infusion over at least 30 minutes or IM inj. Severe cases: 2 g 12 hourly via IV inj or infusion over at least 30 minutes, may be increased to 2 g 8 hourly for very severe infections. Max: 2 g 8 hourly. Usual treatment duration: 7-10 days. Dosage recommendations may vary among countries and individual products (refer to detailed product or local treatment guidelines).
Child: >2 months ≤40 kg: 50 mg/kg 12 hourly for 10 days, may increase frequency to 8 hourly in more severe cases; >40 kg: Same as adult dose. Dosage recommendations may vary among countries and individual products (refer to detailed product or local treatment guidelines).
Renal impairment: Patients undergoing haemodialysis: 1 g as loading dose on the 1st day, followed by 0.5 g 24 hourly; administer after dialysis during dialysis days. In patients with mild to moderate renal insufficiency, initial dose recommended is similar in patients with normal renal function.

CrCl (ml/min)	Dosage Recommendation
<11	Maintenance: 0.25-1 g 24 hourly.
11-29	Maintenance: 0.5-2 g 24 hourly.
30-60	Maintenance: 0.5-2 g 24 hourly or 2 g 12 hourly.

Reconstitution: IV: Reconstitute vials labelled as 500 mg with 5 mL and 1 g or 2 g with 10 mL of compatible IV diluent to yield a final concentration of 100 mg/mL (500 mg and 1 g vial) or 160 mg/mL (2 g vial). May further dilute in a compatible IV infusion fluid. IM: Reconstitute vials labelled as 500 mg or 1 g with 1.3 mL or 2.4 mL, respectively, of sterile water for inj, NaCl 0.9%, dextrose 5% in water, lidocaine 0.5% or 1%, or bacteriostatic water for inj to a yield a final concentration of 280 mg/mL.
Incompatibility: Incompatible with metronidazole, aminophylline, gentamicin, tobramycin, netilmicin, vancomycin, and ampicillin (at a concentration >40 mg/mL).

Parenteral
Urinary tract infections
Adult: Dose and route of administration may vary according to the severity of the infection, renal function and general condition of the patient. For complicated and uncomplicated cases: Mild to moderate cases: 0.5-1 g 12 hourly via IV inj or infusion over at least 30 minutes or IM inj. Severe cases: 2 g 12 hourly via IV inj or infusion over at least 30 minutes, may be increased to 2 g 8 hourly for very severe infections. Max: 2 g 8 hourly. Usual treatment duration: 7-10 days. Dosage recommendations may vary among countries and individual products (refer to detailed product or local treatment guidelines).
Child: >2 months ≤40 kg: 50 mg/kg 12 hourly for 10 days, may increase frequency to 8 hourly in more severe cases; >40 kg: Same as adult dose. Dosage recommendations may vary among countries and individual products (refer to detailed product or local treatment guidelines).
Renal impairment: Patients undergoing haemodialysis: 1 g as loading dose on the 1st day, followed by 0.5 g 24 hourly; administer after dialysis during dialysis days. In patients with mild to moderate renal insufficiency, initial dose recommended is similar in patients with normal renal function.

CrCl (ml/min)	Dosage Recommendation
<11	Maintenance: 0.25-1 g 24 hourly.
11-29	Maintenance: 0.5-2 g 24 hourly.
30-60	Maintenance: 0.5-2 g 24 hourly or 2 g 12 hourly.

Reconstitution: IV: Reconstitute vials labelled as 500 mg with 5 mL and 1 g or 2 g with 10 mL of compatible IV diluent to yield a final concentration of 100 mg/mL (500 mg and 1 g vial) or 160 mg/mL (2 g vial). May further dilute in a compatible IV infusion fluid. IM: Reconstitute vials labelled as 500 mg or 1 g with 1.3 mL or 2.4 mL, respectively, of sterile water for inj, NaCl 0.9%, dextrose 5% in water, lidocaine 0.5% or 1%, or bacteriostatic water for inj to a yield a final concentration of 280 mg/mL.
Incompatibility: Incompatible with metronidazole, aminophylline, gentamicin, tobramycin, netilmicin, vancomycin, and ampicillin (at a concentration >40 mg/mL).

Parenteral
Febrile neutropenia
Adult: Dose and route of administration may vary according to the severity of the infection, renal function and general condition of the patient. As empiric treatment: Mild to moderate cases: 1 g 12 hourly via IV inj or infusion over at least 30 minutes or IM inj. Severe cases: 2 g 12 hourly via IV inj or infusion over at least 30 minutes, may increase to 2 g 8 hourly for very severe infections. Max: 2 g 8 hourly. Usual treatment duration: 7 days or until neutropenia is resolved. Dosage recommendations may vary among countries and individual products (refer to detailed product or local treatment guidelines).
Child: >2 months ≤40 kg: 50 mg/kg 8 hourly for 7-10 days; >40 kg: Same as adult dose. Dosage recommendations may vary among countries and individual products (refer to detailed product or local treatment guidelines).
Renal impairment: Patients undergoing haemodialysis: 1 g 24 hourly; administer after dialysis during dialysis days. In patients with mild to moderate renal insufficiency, initial dose recommended is similar in patients with normal renal function.

CrCl (ml/min)	Dosage Recommendation
<11	Maintenance: 0.25-1 g 24 hourly.
11-29	Maintenance: 0.5-2 g 24 hourly.
30-60	Maintenance: 0.5-2 g 24 hourly or 2 g 12 hourly.

Reconstitution: IV: Reconstitute vials labelled as 500 mg with 5 mL and 1 g or 2 g with 10 mL of compatible IV diluent to yield a final concentration of 100 mg/mL (500 mg and 1 g vial) or 160 mg/mL (2 g vial). May further dilute in a compatible IV infusion fluid. IM: Reconstitute vials labelled as 500 mg or 1 g with 1.3 mL or 2.4 mL, respectively, of sterile water for inj, NaCl 0.9%, dextrose 5% in water, lidocaine 0.5% or 1%, or bacteriostatic water for inj to a yield a final concentration of 280 mg/mL.
Incompatibility: Incompatible with metronidazole, aminophylline, gentamicin, tobramycin, netilmicin, vancomycin, and ampicillin (at a concentration >40 mg/mL).

Hypersensitivity to cefepime or other cephalosporins; history of severe hypersensitivity reactions (e.g. anaphylactic reaction) to other β-lactam antibacterial agents (e.g. penicillins, carbapenems, monobactams).

Patient with history of non-severe hypersensitivity to other β-lactam agents, asthma, allergic diathesis, seizure disorder, gastrointestinal disease (particularly colitis). Neonates, children, and elderly. Renal impairment. Pregnancy and lactation. Monitoring Parameters Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Monitor renal function. Assess for signs and symptoms of anaphylaxis during the initial dose.

Significant: Elevated INR; fungal or bacterial superinfection (prolonged use). Blood and lymphatic system disorders: Anaemia, eosinophilia. Gastrointestinal disorders: Diarrhoea, nausea, vomiting. General disorders and administration site conditions: Localised reactions (e.g. phlebitis, inflammation and/or pain), fever. Investigations: Increased AST, ALT, alkaline phosphatase, blood bilirubin; prolonged partial thromboplastin time. Nervous system disorders: Headache. Skin and subcutaneous tissue disorders: Rash, pruritus.
Potentially Fatal: Hypersensitivity reactions; pseudomembranous colitis, Clostridium difficile-associated diarrhoea; neurotoxicity including encephalopathy, aphasia, myoclonus, seizures, non-convulsive status epilepticus (particularly in patients with renal impairment who did not receive appropriate dosage adjustment).

Symptoms: Encephalopathy (disturbance of consciousness including confusion, stupor, hallucinations, and coma), myoclonus, seizures, neuromuscular excitability, nonconvulsive status epilepticus. Management: Supportive treatment. In case of severe overdose, particularly in patients with renal insufficiency, haemodialysis is recommended and not peritoneal dialysis.

May potentiate the action of coumarin anticoagulants. May enhance the nephrotoxic effects of aminoglycosides or potent diuretics (e.g. furosemide).

May cause positive Coombs test (without evidence of haemolysis) and false-positive reaction for urinary glucose with copper reduction tests (e.g. Benedict's solution, Fehling's solution, Clinitest^® tab).

Cefepime is a broad-spectrum, bactericidal antibiotic that is active against a wide range of Gram-positive and Gram-negative bacteria, including multiple strains resistant to aminoglycosides or 3rd generation cephalosporins. It acts by inhibiting the bacterial cell wall synthesis by binding to 1 or more penicillin-binding proteins (PBP) which interrupts the final transpeptidation step of peptidoglycan synthesis, leading to bacterial cell lysis and death. It is highly resistant to most β-lactamases.
Absorption: Rapidly and completely absorbed following IM inj. Time to peak plasma concentrations: 1-2 hours (IM); 0.5 hours (IV).
Distribution: Widely distributed in body fluids and tissues; highly concentrated in bile. Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 18 L. Plasma protein binding: Approx 20%.
Metabolism: Metabolised in the liver to N-methylpyrrolidinium, which is rapidly converted to the N-oxide.
Excretion: Via urine (85% as unchanged drug; <1% as N-methylpyrrolidinium, 6.8% as N-methylpyrrolidinium-N-oxide, 2.5% as cefepime epimer). Elimination half-life: Approx 2 hours.

Parenteral: Store intact vials between 20-25°C. Protect from light. Once reconstituted, may store solutions diluted in NaCl 0.9% and dextrose 5% in water solutions between 20-25°C for 24 hours or between 2-8°C for 7 days. Storage recommendations may vary among individual products. Refer to detailed product guidelines.

Cephalosporins

J01DE01 - cefepime ; Belongs to the class of fourth generation cephalosporins. Used in the systemic treatment of infections.