Cefepime Hydrochloride

Indications
Cefepime is indicated in abdominal infections, Respiratory tract infections, Skin and skin structure infections, Urinary tract infections, Empiric therapy for febrile neutropenic patients.

Therapeutic Class
Fourth generation Cephalosporins

Pharmacology
Cefepime inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins (PBPs) which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysis and murein hydrolases) while cell wall assembly is arrested.

Dosage & Administration
Abdominal infections, Respiratory tract infections, Skin and skin structure infections, Urinary tract infections:
Adult: Mild to moderate infections: 1-2 g daily in 2 divided doses. Severe infections: Up to 4 g daily in 2 divided doses. Doses are given by deep IM inj or IV infusion over at least 30 min.
Child: Neonates: 30 mg/kg 12 hrly, may increase to 50 mg/kg for Pseudomonas infections; >30 days Mild to moderate infections: 100 mg/kg daily in 2 divided doses. Severe infections: Up to 150 mg/kg daily in 2 or 3 divided doses. Total dose should not exceed the recommended adult dosage.
Empiric therapy for febrile neutropenic patients:
Adult: Up to 6 g daily in 3 divided doses. Doses are given by deep IM inj or IV infusion over at least 30 min.

Interaction
Increased potential for nephrotoxicity and ototoxicity of aminoglycosides. Increased risk of nephrotoxicity with potent diuretics (e.g. furosemide).

Contraindications
Hypersensitivity to cefepime or other cephalosporins.

Side Effects
Headache, rash, diarrhoea, nausea, vomiting, local reactions (e.g. phlebitis, pain and/or inflammation), neutropenia, positive direct Coombs' test.

Pregnancy & Lactation
Pregnancy Category B. Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

Precautions & Warnings
Hypersensitivity to penicillins or other β-lactam antibiotics. Patient with history of seizure disorder, history of GI disease, particularly colitis. Renal impairment. Pregnancy and lactation. Prolonged use may result in overgrowth of non-susceptible organisms.

Overdose Effects
Symptoms: Encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, neuromuscular excitability and non-convulsive status epilepticus.
Management: Supportive treatment. Haemodialysis is recommended in case of renal insufficiency.

Reconstitution
IV infusion: Add 5 mL, 10 mL, or 10 mL of a compatible IV soln to a vial labeled as containing 500 mg, 1 g, or 2 g, respectively, to provide soln containing approx 100 mg/mL, 100 mg/mL, or 160 mg/mL of the drug, respectively. The appropriate dose of the drug should then be added to a compatible IV soln.
IM inj: Add 1.3 mL or 2.4 mL of an appropriate diluent (e.g. sterile water for inj, NaCl 0.9%) to a vial labeled as containing 500 mg or 1 g respectively, to provide a soln containing approx 280 mg/mL.

Storage Conditions
Store between 20-25°C. Protect from light.