Zepime

Cefepime hydrochloride.

Each vial contains: Cefepime (as Hydrochloride) with Arginine USP 500 mg, 1 g, or 2 g.
Cefepime is a white to off-white, non-hygroscopic, crystalline powder. Freely soluble in water.

Pharmacology: Pharmacokinetics: Cefepime is administered by injection as the hydrochloride. It is rapidly and almost completely absorbed following intramuscular injection and mean peak plasma concentrations of about 14 and 30 μg per mL have been reported about 1.5 hours after doses of 500 mg and 1 g respectively. Within 30 minutes of intravenous administration of similar doses, peak plasma concentrations of about 40 mg and 80 μg per mL are achieved. The plasma half-life of Cefepime is approximately 2 hours and is prolonged in patients with renal impairment. About 20% of Cefepime is bound to plasma proteins.
Cefepime is widely distributed in body tissue and fluids. High concentrations are achieved in bile. Low concentrations have been detected in breast milk.
Cefepime is eliminated principally by the kidneys and about 85% of a dose is recovered unchanged in the urine. Cefepime is substantially removed by haemodialysis.
Microbiology: Antimicrobial Action: Cefepime is a fourth-generation cephalosporin antibiotic and is active against wide of Gram-positive and Gram-negative aerobic organisms. Against Gram-positive cocci, its activity is similar to that of Cefotaxime and includes staphylococci (but not methicillin-resistant Staphylococcus aureus) and streptococci. Against Enterobacteriaceae, it has a broader spectrum of activity against organisms producing chromosomally mediated beta-lactamases such as Enterobacter spp. and Proteus vulgaris. Against Pseudomonas aeruginosa, it has a similar or slightly less activity than ceftazidime, although it may be active against some strains resistant to ceftazidime.

For empiric monotherapy in febrile neutropenia patients.
Cefepime is a fourth generation cephalosporin antibiotic used in the treatment of infections due to susceptible organisms. They include infections due to suspected gram-negative organisms resistant to older cephalosporins (sepsis, pneumonia, meningitis) of the urinary tract, respiratory tract and skin.

Cefepime is given as the hydrochloride by deep intramuscular injection, or intravenously by infusion over at least 30 minutes. Doses are expressed in terms of the equivalent amount of Cefepime. The usual dose 1 to 2 g daily in 2 divided doses for mild to moderate infections, increased to 4g daily in 2 divided doses in severe infections, although up to 6 g daily in 3 divided doses has been given for febrile neutropenia. Children aged over 2 months and weighing up to 40 kg may be given 50 mg per kg body weight twice daily; this dose may be given three times daily for febrile neutropenia.
Dosage should be modified in renal impairment. After a normal initial loading dose the maintenance dosage should be adjusted according to the patient's creatinine clearance and the severity of the infection: creatinine clearance 30 to 60 mL per minute, 0.5 to 2 g every 24 hours; 11 to 29 mL per minute, 0.5 to 1 g every 24 hours; and 10 mL per minute or less, 0.25 to 0.5 g every 24 hours.
Patients undergoing haemodialysis should be given a dose after each dialysis sessions, while those undergoing continuous ambulatory peritoneal dialysis should receive normal recommended doses at intervals of 48 hours.
Or as prescribed by the physician.

Patients who receive an overdose should be carefully observed and given supportive treatment. In the presence of renal insufficiency, hemodialysis is recommended to aid in the removal of Cefepime from the body.
Symptoms of overdose include encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, and neuromuscular excitability.

Cefepime is contraindicated in patients who are hypersensitive to the drug or other cephalosporins and should be used with caution in patients with a history of hypersensitivity to penicillins. Anaphylaxis has been reported in a few patients receiving Cefepime. If a hypersensitivity reaction occurs during Cefepime therapy, the drug should be discontinued and the patient treated with appropriate therapy (e.g. epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen) as indicated.

Cefepime is a fourth generation cephalosporins and about 10% of penicillin-sensitive patients may also be allergic to cephalosporins although the true incidence is uncertain; great care should be taken if Cefepime is to be given to such patients. Care is also necessary in patients with history of allergy.
Cefepime should be given with caution to patients with renal impairment; a dosage reduction may be necessary. Renal and haematological status should be monitored especially during prolonged and high-dose therapy. Other cephalosporins and cephamycins (ceforanide, cefotetan, cefoxitin, and cefpirome) may interfere with the Jaffe method of measuring creatinine concentrations and may produce falsely high values; this should be borne in mind when measuring renal function.

There are no adequate and well-controlled studies of Cefepime use in pregnant women. Animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Cefepime is excreted in human breast milk in very low concentrations (0.5 mcg/mL). Caution should be exercised when Cefepime is administered to a nursing woman.

Cefepime has similar adverse effects as cefalotin. The most common are hypersensitivity reactions, including skin rashes, urticaria, eosinophilia, fever, reactions resembling serum sickness with prolonged parenteral administration and anaphylaxis. There may be a positive response to the Coomb's test although haemolytic anaemia rarely occurs. Neutropenia and thrombocytopenia have occasionally have reported. Agranulocytosis has been associated rarely with some cephalosporins. Bleeding complications related to hypoprothrombinaemia and/or platelet dysfunction have occurred especially with cephalosporins and cephamycins have an N-methylthiotetrazole side-chain, including cefamandole, cefbuperazone, cefmenoxime, cefmetazole, cefonicid, cefoperazone, ceforanide, cefotetan, cefpiramide, and latamoxef. The presence of methylthiadiazole thiol side-chain, as in cefazolin, or an N-methylthiotriazine ring, as in ceftriaxone, might also be associated with such bleeding disorders.
Transient increases in liver enzyme values have been reported. Hepatitis and cholestatic jaundice have occurred rarely with some cephalosporins.
Convulsions and other signs of CNS toxicity have been associated with high doses, especially in patients with severe renal impairment.
Gastrointestinal adverse effects such as nausea, cramps, vomiting and diarrhea have been reported rarely. Prolonged use may result in overgrowth of non-susceptible organisms and, as with other broad-spectrum antibiotics, pseudomembranous colitis may develop.
There may be pain at the injection site after intramuscular administration and thrombophlebitis has occurred following infusion of cephalosporins.

The use of nephrotoxic drugs such as the aminoglycosides gentamicin and tobramycin may increase the risk of kidney damage with Cefepime. There is also some evidence for enhanced nephrotoxicity with the loop diuretic furosemide, but this is less certain than for furosemide with cefaloridine. Similarly to the penicillins, the renal excretion of Cefepime and many other cephalosporins is inhibited by probenecid. There may be antagonism behavior Cefepime and bacteriostatic antibacterials.

Direction for Reconstitution: For 500 mg vial: I.M: Add 1.3 mL of Sterile Water for Injection.
I.V: Add 5 mL of Sterile Water for Injection.
Discard any unused portion after reconstitution.
For 1 g and 2 g vial: I.M: Add 2.4 mL of Sterile Water for Injection.
I.V: Add 10 mL of Sterile Water for Injection.
Discard any unused portion after reconstitution.

Store at temperatures not exceeding 30°C.
Store in airtight containers and protect from light.

Cephalosporins

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

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