They are based on the antibacterial activity and pharmacokinetic characteristics of cefepime. They take into account both the clinical studies to which the drug has given rise and its place in the range of antibacterial products currently available.

They include infections caused by germs sensitive to cefepime

· In the adult

O sepsis and bacteraemias

O low respiratory infections, community and severe pneumonia

O urinary infections, complicated and uncomplicated

O febrile episodes in neutropenic patients

O biliary infections.

· In the infant over two months and the child

O febrile episodes in neutropenia when the expected duration of neutropenia is short

Official recommendations concerning the appropriate use of antibacterials should be taken into account.
Dosage

· Renal function, normal

In the adult

The usual dosages, recommended in monotherapy or in association are the following

Type of infections

Dose, Unit, Way

Frequency of administration

Community respiratory infections, uncomplicated pyelonephritis

1 g IV, or IM

2 times per day

Severe Infections

· Septicemia / bacteraemia

· Pneumonia

· Complicated urinary infections

· Biliary infections

2 g, IV

2 times per day

Febrile episode in patients, neutropenic patients

2 g, IV

2 to 3 times a day

Severe infections in Pseudomonas

2 g, IV

3 times per day

* The dosage of 2 g, 3 times a day was administered only as monotherapy.

In infants over 2 months of age and child
50 mg / kg IV, 3 times daily. The clinical data available in infants and children do not recommend the use of cefepime as monotherapy.

· Renal insufficiency

Cefepime is eliminated by the renal route, exclusively by glomerular filtration. Therefore, in patients with renal insufficiency (glomerular filtration 32 mg / l

Pneumococcus: S £ 0.5, mg / l and R> 2 mg / l (parenteral)
The prevalence of acquired resistance may vary according to geography and time for some species. It is therefore useful to have information on the prevalence of local resistance, especially for the treatment of severe infections. These data can only provide guidance on the probabilities of the susceptibility of a bacterial strain to this antibiotic.

When the variability of the resistance prevalence in France is known for a bacterial species, it is indicated in the table below

Categories

Frequency of resistance, acquired in France (> 10%) (extreme values)

SENSITIVE SPECIES

Gram-positive aerobes

Staphylococcus méti-S

Streptococcus

Streptococcus pneumoniae

15 - 35%

Gram-negative Aerobes

Acinetobacter baumannii

Branhamella catarrhalis

Citrobacter freundii

Citrobacter koseri

Enterobacter

Escherichia coli

Haemophilus influenzae

Klebsiella

0 - 20%

Morganella morganii

Neisseria

Proteus, mirabilis

Proteus, vulgaris

Providencia

Salmonella

Serratia

Shigella

Categories

Frequency of resistance acquired in France (> 10%) (values, extremes)

Anaerobes

Clostridium perfringens

Fusobacterium

Peptostreptococcus

Prevotella

0.15

MODERATELY SENSITIVE SPECIES

(In vitro sensitivity, intermediate)

Gram-negative Aerobes

Pseudomonas aeruginosa

15 - 35%

RESISTANT SPECIES

Gram-positive aerobes

Enterococci

Listeria

Staphylococcus meti-R; *

Gram-negative Aerobes

Burkholderia cepacia

Stenotrophomonas maltophilia

Anaerobes

Bacteroides fragilis

Clostridium difficile

* The frequency of resistance to methicillin is approximately 30 to 50% of the total staphylococci and is found mainly in hospital.
Not applicable.

This medication MUST NEVER BE USED in case of allergy

· Antibiotics in the cephalosporin group (see section 4.4).
· To L-Arginine.

· The occurrence of any allergic manifestation requires cessation of treatment.

· The prescription of cephalosporins requires an examination for discovery. Allergy to penicillins being crossed with that of cephalosporins in 5 to 10% of cases

O the use of cephalosporins must be extremely cautious in patients, penicillin-sensitive, strict medical supervision is required from the first; administration
O the use of cephalosporins should be avoided, formally in subjects with a history of immediate allergy to cephalosporins. In case of doubt, the presence of the physician with the patient is essential to the first administration in order to treat a possible anaphylactic reaction.
· Cases of diarrhea associated with Clostridium difficile are reported with the use of many antibiotics, including AXEPIM®. The severity of these diarrhea may extend to a life-threatening pseudomembranous colitis. It is important that this diagnosis is evoked in patients with diarrhea during or after an antibiotic, since cases have been observed up to 2 months after discontinuation of treatment

This accident, which is rare with cephalosporins, requires the immediate cessation of treatment and the initiation of an appropriate specific antibiotic therapy. In this case, the administration of products promoting fecal stasis must absolutely be avoided.

· In case of renal insufficiency, for creatinine clearances less than or equal to 50 ml / min, adjust dosage (see Posology and method of administration) to avoid clinical effects due to Antibiotic high.

Elderly: Of the 6400 adults enrolled in clinical trials, 35% were over 65 years old and 16% were over 75 years of age. The distribution of cefepime in the elderly (> 65 years) was studied. In subjects with normal renal functions no dosage adjustment should be considered. However, renal function degrading with age, dosage, should be adapted to the state of renal function of the patient (see section: Pharmacokinetic properties).

It is prudent to monitor renal function in association with cefepime with potentially nephrotoxic antibiotics (aminoglycosides in particular) or with potent diuretics.

· Interference with biological examinations

O A positive Coombs test, without evidence of haemolysis, was reported in 18.7% of patients treated with cefepime twice daily. >
O A false positive reaction which may occur during the search for glycosuria, and the methods of assay using glucose oxidase should preferably be used.
Special Problems of the INR imbalance

Many cases of increased oral anticoagulant activity have been reported in patients receiving antibiotics. The marked infectious or inflammatory context, age and general condition of the patient appear as risk factors. In these circumstances, it is difficult to distinguish between infectious pathology and its treatment in the onset of INR imbalance, although some classes of antibiotics are more involved: these include fluoroquinolones , Macrolides, cyclins, cotrimoxazole and certain cephalosporins.

Do not mix in the same container with other medicines Intravenous administration: Cefepime can be dissolved with water for injectable preparation or any other compatible solvent Compatibility Cefepime is compatible With the following solvents and solutions: Sodium Chloride 0.9% (with or without glucose 5%), glucose 5 or 10%, Ringer's liquid (with or without glucose 5%), Sodium lactate M / 6 - Cefepime may be given concomitantly with other antibiotics provided that the same syringe, infusion or injection site is not used.

Accidental overdose, which may be manifested as evidence of encephalopathy (see section 4.4), has been observed in patients with impaired renal function, and receiving dosages in excess of recommended doses.

In case of severe overdose, particularly in patients with impaired renal function, serum levels of cefepime may be reduced by hemodialysis. Peritoneal dialysis is of no efficacy

Pregnancy

Due to the expected benefit, the use of cefepime may be considered during pregnancy if needed. Indeed, although the clinical data are insufficient, the animal data did not show any effect, malformation or foetotoxicity of cefepime. >
Breastfeeding

Passage into breast milk is low and amounts ingested are much lower than therapeutic doses. Accordingly, breast-feeding is possible if this antibiotic is taken.

However, discontinue breast-feeding (or medication) in the event of diarrhea, candidiasis or rash in the infant.
Moderate and transient hematologic manifestations: frequent anemia, eosinophilia, prolongation of prothrombin time and activated partial thromboplastin time, frequently leucopenia, neutropenia, thrombocytopenia. Cases of agranulocytosis have been reported (incidence not known).
· Allergic reactions: uncommon: urticaria and fever, very rarely anaphylaxis, severe (anaphylactic shock)

Neurological Manifestations: rarely, headache, paresthesia, very rarely, confusion, dizziness, convulsions, taste modification, tinnitus.
As with other beta-lactams, rare cases of reversible encephalopathies (disturbances of vigilance and consciousness which may go as far as coma, hallucinations, myoclonus, convulsive seizures) have been reported. Most cases have occurred in patients with renal insufficiency receiving doses above the recommended doses, in particular, in the elderly (see section 4.3), and the symptoms of neurotoxicity have generally been favorable. Stopping the treatment and / or after hemodialysis. However, there have been some cases of fatal evolution.

· Digestive manifestations: frequently diarrhea, little, frequently nausea, vomiting, candidiasis, buccales, very rarely abdominal pain, colitis in particular pseudomembranous type, ulceration, buccal. >
Hepatic manifestations: frequent, moderate and transient elevation of ALT and ASAT transaminases, alkaline phosphatases and total bilirubin

· Skin manifestations: frequently rash.

Renal manifestations: infrequent, transient increase in uremia and / or serum creatinine. Rare cases of acute renal failure have been reported.

· Other manifestations reported very rarely

O, hypotension, vasodilation

O, edema, arthralgia

O