Antibioprophylaxis, postoperative endophthalmitis after cataract surgery (see section 5.1)
Official recommendations concerning the appropriate use of antibacterials, including those on antibioprophylaxis in ocular surgery, should be taken into account.
Intra-camerular line. A bottle for single use only.

Dosage

Adults

The recommended dosage is 0.1 ml of reconstituted solution (see section Instructions for Use, Handling and Disposal), ie 1 mg of cefuroxime.
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DO NOT INJECT A DOSE HIGHER THAN RECOMMENDED (see section Overdose).

Population, pediatric

The optimal dosage and safety of use of APROKAM has not been established in the pediatric population

Elderly subjects

Dosage adjustment is not necessary

Renal and hepatic impairment

Considering the low dose and negligible systemic passage of cefuroxime, expected after use of APROKAM, no dosage adjustment is necessary.

Mode of administration

APROKAM should be administered after reconstitution by intraocular injection into the anterior chamber of the eye (intra-camerular) by an ophthalmologist under the aseptic conditions recommended for cataract surgery .

After reconstitution, APROKAM should be visually checked for particulate matter or abnormal staining prior to administration.


For instructions on the reconstitution of APROKAM prior to administration, see section "Instructions for use, handling and disposal."
White powder to almost white.

Anti-infectives, Antibiotics, ATC code: S01AA27

Mechanisms of action

Cefuroxime inhibits the synthesis of the bacterial wall by binding to penicillin-binding proteins (PLP). This leads to a stoppage in the biosynthesis of the cell wall (peptidoglycans) causing cell lysis and the death of The bacteria.

Pharmacodynamic / Pharmacokinetic Relationships

For cephalosporins it was shown that the most predictive pharmacokinetic / pharmacodynamic index of in vivo efficacy was the percentage of time (T%), during which the concentration of the free form at cefuroxime was Is located above the minimum inhibitory concentration (MIC) of target bacteria (ie T%> MIC).

After intramuscular injection of 1 mg of cefuroxime, cefuroxime levels in the aqueous humor were greater than the MICs of several species, involved up to 4 to 5 hours after surgery.

Mechanisms of resistance

Bacterial resistance to cefuroxime may be due to one or more of the following mechanisms:
Hydrolysis by beta-lactamases. Cefuroxime may be efficiently hydrolysed by certain extended spectrum beta-lactamases (ESBLs) and by chromosomal beta-lactamases (AmpC) which may be stably induced or depressed in certain species of Gram aerobic bacteria Negative

· Decreased affinity of penicillin-binding proteins for cefuroxime

· Impermeability of the outer wall, which restricts access of cefuroxime to penicillin-binding proteins in Gram-negative bacteria

· Bacterial efflux pumps.

Methicillin-resistant Staphylococcus (MRSA) is resistant to the currently available beta-lactam antibiotics, including cefuroxime.


Strains of H. influenzae, resistant to ampicillin without production of beta-lactamase (BLNAR) should be considered resistant to cefuroxime despite apparent sensitivity in vitro. >

Critical Concentrations

The list of micro-organisms listed below took into account the indication (see section Therapeutic indications)

APROKAM should be used only intramuscularly and should not be used to treat systemic infections (see section 4.4), critical clinical concentrations are not transferable to this route. The values ​​of the epidemiological thresholds (ECOFF), distinguishing the population from wild strains of strains isolated with acquired resistances, are as follows:
ECOFF (mg / L)

Staphylococcus aureus

≤ 4

Streptococcus pneumoniae

≤ 0.125

E. coli

≤ 8

Proteus mirabilis

≤ 4

H. influenzae

≤ 2

The sensitivity of staphylococci to cefuroxime is deduced from sensitivity to methicillin

The sensitivity of the groups A, B, C and G streptococci can be deduced from their susceptibility to benzylpenicillin.
Information from clinical trials

A randomized, prospective, randomized, partial, multicenter blind study in cataract surgery was performed on 16,603 patients. Twenty-nine patients (24 in the "cefuroxime-free" group and 5 in the "cefuroxime by intra-camerular" group) had endophthalmitis including 20 (17 in the "cefuroxime-free" group and 3 in the The group "cefuroxime by injection, intra-camerular") were considered to have infectious endophthalmitis, proven. Of these 20 proven endophthalmitis, 10 patients were in the group "placebo eye drops and cefuroxime", 7 patients, in the group "levofloxacin eye drops and without cefuroxime", 2 patients in the group, "placebo eye drops and cefuroxime; Intra-camerular "and 1 patient in the group" levofloxacin eye drops and cefuroxime intra-camerular ". Prophylaxis of a 1 mg solution of cefuroxime with 0.1 ml of sodium chloride 9 mg / ml (0.9%) per intra-arterial route decreased the risk of endophthalmitis Postoperative follow-up of an equal factor to 4.92.
Two prospective studies (Wedje, 2005 and Lundström 2007) and five retrospective studies are in support of the pivotal study, ESCRS, to further substantiate the efficacy of cefuroxime administered intra-camerally in prevention Of postoperative endophthalmitis

Not applicable.

Hypersensitivity to cefuroxime or antibiotics in the cephalosporin group

APROKAM should be used only by intra-camerular route.

Due to a possible risk of a cross-allergic reaction, special precaution should be taken in patients with a history of allergic reactions to penicillins or other beta-lactams. Br>

In patients at risk, infections due to resistant strains, eg patients with infection or colonization with MRSA (Staphylococcus, aureus resistant to meticillin), another, prophylactic antibiotic treatment must be Considered.

In the absence of data in specific patient groups (high-risk patients, infections, patients with complicated cataracts, patients requiring combined procedures, cataract surgery, patients with severe The thyroid, patients with less than 2000 corneal endothelial cells), APROKAM should be used only after a careful evaluation of the benefit / risk ratio. Code>
The use of cefuroxime should not be considered as an isolated measure because other precautions are equally important, such as antiseptic prophylactic treatment.

No endothelial and corneal toxicity has been reported at the recommended concentration of cefuroxime, but this risk can not be excluded and during postoperative monitoring physicians should keep this potential risk in mind. >

Systemic exposure expected to be negligible, systemic interactions are unlikely

No incompatibility with the products most frequently used in cataract surgery has been reported in the literature

This medicinal product must not be mixed with other medicinal products except as indicated in the section Instructions for use, handling and disposal Inject into the vial 5 ml of solution for injection of Chloride, sodium 9 mg / ml (0.9%) following the rules of asepsis.
The reconstituted solution must be visually inspected and used only if it is colorless to yellowish and free of visible particle

The reported cases of overdosage are those described in the literature on incorrect dilution and unauthorized use of cefuroxime for systemic use.
An overdose of cefuroxime (3 times the recommended dose) was inadvertently administered intra-camerally in 6 patients following an error of dilution of a masterly preparation of cefuroxime. These injections did not cause any detectable adverse effect in all patients, even in the ocular tissues

Toxicity data are available, following intra-cameral injection, during cataract surgery at doses 40 to 50 times, greater than that recommended in cefuroxime, in 6 patients, after dilution errors. The initial mean visual acuity was 20/200. Severe inflammation of the anterior segment was present, and the optical coherence tomography of the retina showed significant macular edema. Six weeks after surgery, visual acuity averaged 20/25. The macular profile in optical coherence tomography returned to normal. However, a 30% decrease in scotopic electroretinography was observed in all patients.

Administration of cefuroxime, incorrectly diluted (10-100 mg per eye) in 16 patients, resulted in ocular toxicity with corneal edema, which in a few weeks resulted in a transient increase in ocular pressure, Loss of endothelial cells, and changes to electroretinography. A number of these patients had severe and permanent vision loss.


There are no data on the effects of cefuroxime sodium on fertility in man. Reproductive studies in animals have shown no effect on fertility.

Pregnancy

There are limited data on the use of cefuroxime in pregnant women. Studies in animals have shown no deleterious effect on embryonic or fetal development. Cefuroxime: reaches the embryo or fetus through the placenta. None, effect during pregnancy is expected, as systemic exposure to cefuroxime following use of APROKAM is negligible. APROKAM can be used during pregnancy.
Breastfeeding

Cefuroxime can be excreted in human milk in very low amounts. Adverse effects at therapeutic doses are not expected after use of APROKAM. Cefuroxime may be used during breastfeeding.

No particular adverse effect has been reported in the literature when cefuroxime is administered by injection intra-ocular except the following
Immune system disorders

Very rare (