Necpime

Necpime

cefepime

Manufacturer:

Nectar Lifesciences

Distributor:

Royal Distribution

Marketer:

ESTI Pharma
Full Prescribing Info
Contents
Cefepime.
Description
Each vial contains: Cefepime USP 500 mg or 1 g (as cefepime hydrochloride).
A blend of sterile cefepime hydrochloride & sterile arginine.
Action
Pharmacology: Pharmacodynamics: Cefepime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefepime has a broad spectrum of in vitro activity that encompasses a wide range of Gram-positive and Gram-negative bacteria. Cefepime has a low affinity for chromosomally-encoded beta-lactamases. Cefepime is highly resistant to hydrolysis by most beta-lactamases and exhibits rapid penetration into Gram-negative bacterial cells. Within bacterial cells, the molecular targets of cefepime are the penicillin binding proteins (PBP).
Pharmacokinetics: The average plasma concentrations of cefepime observed in healthy adult male volunteers (n=9) at various time following single 30-minute infusions (IV) of cefepime 500 mg, 1 g and 2 g are summarized in Table 1. Elimination of cefepime is principally via renal excretion with an average (±SD) half-life of 2 (±0.3) hours and total body clearance of 120 (±8) mL/min in healthy volunteers. Cefepime pharmacokinetics are linear over the range 250 mg to 2 g. There is no evidence of accumulation in healthy adult male volunteers (n=7) receiving clinically relevant doses for a period of 9 days.
Absorption: The average plasma concentrations of cefepime and its derived pharmacokinetic parameters after intravenous (IV) administration are portrayed in Table 1.

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Following intramuscular (IM) administration, cefepime is completely absorbed. The average plasma concentrations of cefepime at various times following a single intramuscular injection are summarized in Table 2. The pharmacokinetics of cefepime are linear over the range of 500 mg to 2 g intramuscularly and do not vary with respect to treatment duration. (See Table 2.)

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Distribution: The average steady state volume of distribution of cefepime is 18 (±2) L. The serum protein binding of cefepime is approximately 20% and is independent of its concentration in serum.
Cefepime is excreted in human milk. A nursing infant consuming approximately 1000 mL of human milk per day would receive approximately 0.5 mg of cefepime per day.
Concentrations of cefepime achieved in specific tissues and body fluids are listed in Table 3.

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Metabolism and Excretion: Cefepime is metabolized to N-methylpyrrolidine (NMP) which is rapidly converted to the N-oxide (NMP-N-oxide). Urinary recovery of unchanged cefepime accounts for approximately 85% of the administered dose. Less than 1% of the administered dose is recovered from urine as NMP, 6.8% as NMP-N-oxide, and 2.5% as an epimer of Cefepime. Because renal excretion is a significant pathway of elimination, patients with renal dysfunction and patients undergoing hemodialysis require dosage adjustment.
Toxicology: Preclinical Safety Data: Non-clinical data reveal on special hazard for humans based on studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development. No carcinogenicity studies have been performed. However, there is no evidence to suggest carcinogenic potential.
Microbiology: Cefepime has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections: Aerobic Gram-Negative Microorganisms: Enterobacter, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa.
Aerobic Gram-Positive Microorganisms: Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pneumoniae, Streptococcus pyogenes (Lancefield's Group A Streptococci), Viridans group Streptococci.
The following in vitro data are available, but their clinical significance is unknown.
Cefepime has been shown to have in vitro activity against most isolates of the following microorganisms; however, the safety and effectiveness of cefepime in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials.
Aerobic Gram-Positive Microorganisms: Staphylococcus epidermidis (methicillin-susceptible isolates only), Staphylococcus saprophyticus, Streptococcus agalactiae (Lancefield's Group B Streptococci).
NOTE: Most isolates of Enterococci, eg, Enterococcus faecalis, and methicillin-resistant Staphylococci are resistant to cefepime.
Aerobic Gram-Negative Microorganisms: Acinetobacter calcoaceticus subsp. lwoffii, Citrobacter diversus, Citrobacter freundii, Enterobacter agglomerans, Haemophilus influenzae (including beta-lactamase producing isolates), Hafnia alvei, Klebsiella oxytoca, Moraxella catarrhalis (including beta-lactamase producing isolates), Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia marcescens.
NOTE: Cefepime is inactive against many isolates of Stenotrophomonas (formerly Xanthomonas maltophilia and Pseudomonas maltophilia). Cefepime is inactive against most isolates of Clostridium difficile.
Indications/Uses
Cefepime for injection is indicated in the treatment of the following infections caused by susceptible strains of the following organisms.
Pneumonia (moderate to severe): Caused by Streptococcus pneumoniae, including cases associated with concurrent bacteremia, Pseudomonas aeruginosa, Klebsiella pneumonia or Enterobacter species.
Empiric therapy for febrile neutropenic patients: Cefepime as monotherapy is indicated for empiric treatment of febrile neutropenic patients. In patients at high risk for severe infections (including patients with history of recent bone marrow transplantation, with hypotension at presentation, with an underlying hematologic malignancy or with severe or prolonged neutropenia), antimicrobial monotherapy may not be appropriate.
Uncomplicated and complicated urinary Tract infections (including Pyelonephritis): caused by Escherichia coli or Klebsiella pneumoniae, when the infection is severe, or caused by Escherichia coli, Klebsiella pneumoniae or Proteus mirabilis, when the infection is mild to moderate, including cases associated with concurrent bacteremia with these microorganisms.
Uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin susceptible strains only) or Streptococcus pyogenes.
Complicated intra-abdominal infections (used in combination with metronidazole) caused by Escherichia coli, viridans group Streptococci, Pseudomonas aeruginosa, Klebsiella pneumonia, Enterobacter species or Bacteroides fragilis.
To reduce the development of drug resistant bacteria and maintain the effectiveness of Cefepime for Injection and other antibacterial drugs it should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy.
Dosage/Direction for Use
Method of Administration: Intramuscular (IM)/Intravenous (IV).
The recommended adult and pediatric dosages are outlined in Table 4.

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Patients with Hepatic impairment: No adjustment is necessary for patients with hepatic impairment.
Patients with Renal impairment: In patients with creatinine clearance less than or equal to 60 ml/min, the dose of Cefepime for Injection should be adjusted to compensate for the slower rate of renal elimination. The recommended initial dose should be the same as in patients with normal renal function except in patients undergoing hemodialysis. The recommended doses in patients with renal impairment is given in Table 5.

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In patients undergoing hemodialysis, approximately 68% of the total amount of Cefepime present in the body at the start of dialysis will be removed during a 3 hour dialysis period. The dosage for hemodialysis patients is 1 g on day 1 followed by 500 mg every 24 hours for the treatment of all infections except febrile neutropenia which is 1 g every 24 hours.
Overdosage
Patients who receive an overdose should be carefully observed and given supportive treatment. In the presence of renal insufficiency, hemodialysis, not peritoneal dialysis, is recommended to aid in the removal of cefepime from the body. Accidental overdosing has occurred when large doses were given to patients with impaired renal function. Symptoms of overdose include encephalopathy (disturbance of consciousness including confusion hallucinations stupor, and coma), myoclonus, seizures, neuromuscular excitability and nonconvulsive status epilepticus.
Contraindications
It is contraindicated in patients who have shown immediate hypersensitivity reactions to Cefepime or the Cephalosporin class of antibiotics, penicillins or other beta lactam antibiotics.
Warnings
Hypersensitivity reactions: Before therapy with Cefepime for Injection is instituted, careful inquiry should be made to determine whether the patients has had previous immediate hypersensitivity reactions to Cefepime, Cephalosporins, Penicillins or other drugs. Exercise caution if this product is to be given to penicillin sensitive patients because cross-hypersensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction occurs, discontinue the drug.
Use in patients with renal impairment: In patients with creatinine clearance less than or equal to 60 ml/min, adjust the dose to compensate for slower rate of renal elimination. Because high and prolonged serum cefepime concentrations can occur from usual dosages in patients with renal impairment, the Cefepime dosage should be reduced when it is administered to such patients. Continued dosage should be determined by degree of renal impairment, severity of infection, and susceptibility of the causative organisms.
Clostridium difficile-Associated Diarrhea: CDAD has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
If CDAD is suspected or confirmed ongoing use of antibiotic need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile and surgical evaluation should be instituted as clinically indicated.
Special Precautions
Prescribing Cefepime for Injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is likely to provide benefit to the patient and increases the risk of the development of drug resistant bacteria.
As with other antimicrobials, prolonged use may result in overgrowth of non-susceptible microorganisms. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.
Many cephalosporins, including cefepime, have been associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment or poor nutritional state as well as patients receiving a protracted courses of antimicrobial therapy. Prothrombin time should be monitored in patients at risk, and exogenous vitamin K administered as indicated.
Positive direct Coomb's tests have been reported during treatment with Cefepime for Injection. In hematologic studies or in transfusion cross matching procedures when antiglobulin tests are performed on the minor side or in Coombs' testing of newborns whose mothers have received cephalosporin antibiotics before parturition, it should be recognized that a positive Coombs' test may be due to the drug.
Arginine has been shown to alter glucose metabolism and elevate serum potassium transiently when administered at 33 times the amount provided by the maximum recommended human dose. The effect of lower doses is not presently known.
Effects on ability to drive and use machines: No studies on the effects on that ability to drive and use machines have been performed. However, as this medicine may cause dizziness, patients should be warned to be cautions when driving or operating machinery.
Use In Pregnancy & Lactation
Pregnancy: Cefepime was not teratogenic or embryocidal when administered during the period of organogenesis to rats at doses up to 1000 mg/kg/day (1.6 times the recommended maximum human dose calculated on a mg/m2 basis) or to mice at doses up to 1200 mg/kg (approximately equal to the recommended maximum human dose calculated on a mg/m2 basis) or to rabbits at a dose level of 100 mg/kg (0.3 times the recommended maximum human dose calculated on a mg/m2 basic).
There are, however, no adequate and well-controlled studies of Cefepime use in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Breastfeeding: 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 women.
Adverse Reactions
The following adverse events were thought to be related to Cefepime during Evaluation of the drug in Clinical Trials conducted. (See Table 6.)

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At the higher dose of 2 g every 8 hours, the incidence of probably related events was higher among the 795 patients who received this dose of Cefepime. They considered rash (4%), diarrhea (3%), nausea (2%), vomiting (1%), pruritus (1%), fever (1%) and headache (1%).
Drug Interactions
Renal function should be monitored carefully if high doses of aminoglycosides are to be administered with Cefepime because of the increased potential of nephrotoxicity and ototoxicity of aminoglycoside antibiotics. Nephrotoxicity has been reported following concomitant administration of other cephalosporins with potent diuretics such as furosemide.
The administration of cefepime may result in a false-positive reaction for glucose in the urine. It is recommended that glucose tests based on enzymatic glucose oxidase reactions be used.
Caution For Usage
Instructions for use: Direction for Constitution: For Intramuscular Administration: Cefepime for injection USP 1 g should be constituted with 2.4 ml of SWFI & Cefepime for injection USP 500 mg should be constituted with 1.3 mL of SWFI.
For Intravenous Administration: Cefepime for injection USP 1 g should be constituted with 10 ml of SWFI & Cefepime for injection USP 500 mg should be constituted with 5 ml of SWFI.
Storage
Store in dry place at temperature below 30°C.
MIMS Class
ATC Classification
J01DE01 - cefepime ; Belongs to the class of fourth generation cephalosporins. Used in the systemic treatment of infections.
Presentation/Packing
Powd for inj (vial) (white to pale yellow) 500 mg x 1's. 1 g x 1's.
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