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

They are limited to infections caused by organisms known to be sensitive, in particular to certain situations where the bacterial species responsible for infection can be multiple and / or resistant to the antibiotics currently available.
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On this basis, this medicinal product is of particular interest in the following indications:

· Acute otitis media of the adult

· Acute maxillary sinusitis and other forms of sinusitis

· Superinfections of acute bronchitis of the patient at risk, in particular chronic ethyl alcohol, tobacco, elderly, over 65 years, in case of evolutive risk or in second;
· Exacerbations of chronic bronchopneumonia

Acute pneumonia of the at-risk patient, in particular chronic ethyl alcohol, tobacco, over 65 years of age or with swallowing disorders

Acute recurrent cystitis, uncomplicated cystitis of the woman and pyelonephritis, uncomplicated acute from germs, sensitive

· High gynecological infections, in combination with another active antibiotic on Chlamydiae (see section CAUTIONS AND PRECAUTIONS for safe use)

· Periodontitis

· Severe stomatal infections: abscess, phlegmons, cellulitis

· Relay treatment of the injectable route.

Official recommendations concerning the appropriate use of antibacterials should be taken into account.
Posology expressed in amoxicillin

ADULTS (weight ≥ 40 kg)

In the patient with normal renal function

· 2 g / day in 2 taken in the following indications

O, acute maxillary sinusitis

O superinfections of acute bronchitis of the patient at risk, in particular chronic ethyl, tobacco, elderly, over 65 years, in case of evolutive risk or in second;
O Exacerbations of chronic bronchopneumonia

O, periodontitis.

· 3 g / day in 3 taken in the following indications

O other forms of sinusitis

O, otitis media acute

Acute recurrent cystitis, uncomplicated cystitis of the woman and pyelonephritis, uncomplicated acute germs, sensitive

O, high gynecological infections, in combination with another active antibiotic on Chlamydiae (see section CAUTIONS AND PRECAUTIONS for safe use)

O: severe stomatal infections: abscess, phlegmons, cellulitis

Acute pneumonia of the patient at risk, in particular chronic ethyl alcohol, tobacco, over 65 years of age or with swallowing disorders

O, relay treatment of the injectable route.

In patients with renal insufficiency

Clearance of creatinine

Scheme
Greater than 30 ml / min.

No, dosage adjustment required

Between 10 and 30 ml / min.

1 g / 125 mg every 12 to 24 hours.

Less than 10 ml / min.

For patients treated or not by hemodialysis, the conditions of use have not been established.

In the elderly patient

No dose adjustment unless creatinine clearance is ≤ 30 ml / min. (See Posology in patients with renal insufficiency).

Administration mode

Oral use.

At each dose, the 2 tablets must be taken at the same time.

Take the medication preferably at the beginning of the meal.
Pharmacotherapeutic group, ANTIBACTERIANS FOR SYSTEMIC USE, ATC code, J01CR02.

This drug is a combination of amoxicillin and clavulanic acid, a potent, beta-lactamase inhibitor. Clavulanic acid rapidly and irreversibly inhibits most beta-lactamases produced by Gram-positive and Gram-negative bacteria.
SPECTRUM OF ACTIVITY, ANTIBACTERIAL

Critical concentrations separate sensitive strains from strains of intermediate sensitivity and the latter from resistant strains

S $ 4; mg / l; and R> 16; mg / l
MIC, pneumococcus: S £ 0.5, mg / l and R> 2 mg / l

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

Corynebacterium diphtheriae

Enterococcus faecalis

Erysipelothrix rhusiopathiae

Listeria monocytogenes

Nocardia asteroids

Staphylococcus méti-S

Streptococcus

Streptococcus bovis

Streptococcus pneumoniae

15 - 35%

Gram-negative Aerobes

Actinobacillus actinomycetemcomitans

Bordetella pertussis

Branhamella catarrhalis

Burkholderia pseudo-mallei

Campylobacter

Capnocytophaga

Citrobacter koseri

Eikenella

Escherichia coli

10 - 30%

Haemophilus influenzae

Haemophilus para-influenzae

Klebsiella

0 - 20%

Neisseria gonorrhoeae

Neisseria meningitidis

Pasteurella multocida

Proteus, mirabilis

10 - 20%

Proteus, vulgaris

Salmonella

0 - 40%

Shigella

0 - 30%

Vibrio cholerae

Categories

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

Anaerobes

Actinomyces

Bacteroides

Clostridium

Eubacterium

Fusobacterium

Peptostreptococcus

Porphyromonas

Prevotella

Propionibacterium acnes

Veillonella

Other

Bartonella

Borrelia

Leptospira

Treponema

MODERATELY SENSITIVE SPECIES

(In vitro sensitivity, intermediate)

Gram-positive aerobes

Enterococcus faecium

40 - 80%

RESISTANT SPECIES

Gram-positive aerobes

Staphylococcus meti-R; *

Gram-negative Aerobes

Acinetobacter

Citrobacter freundii

Enterobacter

Legionella

Morganella morganii

Proteus; rettgeri

Providencia

Pseudomonas

Serratia

Yersinia; enterocolitica

Categories

Other

Chlamydia

Coxiella

Mycobacterium

Mycoplasma

Rickettsia

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

This medicinal product should NEVER be used in cases of

· Allergy to antibiotics of the beta-lactam family (penicillins, cephalosporins): take into account the risk of cross-allergicity with the antibiotics in the group, cephalosporins

· Allergy to any component of the drug

· A history of hepatic involvement related to the association of amoxicillin / clavulanic acid

This medication is GENERALLY NOT RECOMMENDED for use in combination with methotrexate (see section Interactions with other medicinal products and other forms of interaction). Code>
Special warnings

The occurrence of any manifestation, allergic necessitates the cessation of treatment and the setting up of a suitable treatment.

Immuno-allergic reactions, of which severe and sometimes fatal hypersensitivity reactions (anaphylaxis) have been observed exceptionally in patients treated with beta-lactam antibiotics. Code>
Their administration therefore requires an examination for discovery.

In the face of a history of a typical allergy to these products, the contraindication is formal.

Allergy to penicillins is crossed with cephalosporin allergy in 5 to 10% of cases. This leads to the proscription of penicillins when the subject is a known allergic to cephalosporins.


Precautions for use

As with all beta-lactams, regularly check the blood formula when administering high doses of amoxicillin

The administration of high doses of beta-lactams in patients with renal insufficiency or in patients with predisposing factors such as a history of seizures, epilepsy, treatment or meningeal involvement may exceptionally lead to convulsions

For renal insufficiency, for creatinine clearances less than or equal to 30 ml / min, adjust dosage (see section Dosage and Mode of Administration). >

The risk of occurrence of a hepatic adverse effect (cholestasis) is increased, with treatment greater than 10 days and all, especially after 15 days.
In case of prolonged treatment, it is recommended to monitor the liver and kidney functions.

The combination of amoxicillin / clavulanic acid should be used with caution, in case of hepatic impairment

This medicinal product contains 12.27 mg (0.31 mmol) potassium per tablet (24.54 mg per dose): take this into account in people on a diet, hypokalaemic.

Examinations, paraclinics

Impact on biological parameters

A positivity of the direct Coombs test was obtained during treatment with beta-lactams. This may also occur in subjects treated with amoxicillin / clavulanic acid. False positivations of this test linked to the presence of clavulanic acid have also been observed.

A very high concentrations, amoxicillin tends to

· Decrease the results of blood glucose measurements

· Interferes in the determinations of the total serum protein by color reaction

· Give a false positive color reaction in the glycosuria assays by the colorimetric semi-quantitative method

Associations, deprecated

+ Methotrexate

Increased hematological effects and toxicity of methotrexate by inhibition of renal tubular secretion by penicillins

Associations to be taken into account

+ Allopurinol (and by extrapolation, other inhibitors of uricosynthesis)

Increased risk of skin reactions

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.

Not applicable.

The manifestations of overdose may be neuropsychic, renal (crystalluria) and digestive. Treatment is symptomatic by monitoring, particularly balance, hydroelectrolyte. Amoxicillin and clavulanic acid can be eliminated by hemodialysis

Pregnancy

For amoxicillin there are no reliable data for teratogenesis in animals

In clinical studies, epidemiological studies have not revealed any malformative or fetotoxic effects related to the use of amoxicillin

For clavulanic acid, studies in animals have not shown any teratogenic effect. In the absence of teratogenic effect in animals, a malformative effect in the human species is not expected. Indeed, to date, the substances responsible for malformations in the human species have been found to be teratogenic in animals in well-conducted studies of two species

Clinically, the use of clavulanic acid in a limited number of pregnancies has apparently shown no particular malformative or fetotoxic effects to date. However, further studies are needed to evaluate the consequences of exposure during pregnancy.


Accordingly, the combination of amoxicillin / clavulanic acid may be prescribed during pregnancy if necessary.
Breastfeeding

The passage of amoxicillin-clavulanic acid into breast milk is low and the amounts ingested are much lower than the 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.

· Digestive symptoms: nausea, vomiting, possibility of digestive superinfections, Candida, diarrhea, loose stools, dyspepsia and abdominal pain. Some cases of pseudomembranous colitis and haemorrhagic colitis have been reported.

Allergic manifestations include urticaria, eosinophilia, angioedema, discomfort, respiratory disease, serum sickness, vasculitis, exceptionally anaphylactic shock.
· Maculopapular rash of allergic origin or not

Very rarely, some cases of Lyell and Stevens-Johnson syndrome, erythema multiforme, and exfoliative dermatitis have been reported.

These cutaneous manifestations may be more frequent and / or more intense in patients with infectious mononucleosis or leukemia, the evolving lymphoid.


· Other manifestations have been reported, more rarely

O cases of hepatitis, usually cholestatic, or mixed, have been occasionally reported.These cases appear to occur more readily in elderly and male patients and in treatment of more than 10 days and in particular For treatments, greater than 15 days. Symptoms, such as jaundice which appears to be constant, appear during or at the end of treatment, but may occur a few weeks after discontinuation. The histopathological examination of the liver usually reveals a centro-lobular cholestasis. The evolution is generally favorable but can be extended by a few weeks.
Some extremely rare cases of fatal evolution have been observed:

O moderate and asymptomatic increases in ASAT, ALAT or alkaline phosphatase

O interstitial nephritis, acute

Leucopenia, neutropenia, agranulocytosis, haemolytic anemia, thrombocytopenia, reversible
Cases of seizures have been reported exceptionally (see Warnings and Precautions for Use).

Reporting of suspected adverse reactions

The reporting of suspected adverse reactions after authorization of the drug is important. It allows continuous monitoring of the ratio, benefit / risk of the drug. Health professionals report any suspected adverse effects via the national reporting system: National Agency for the Safety of Medicines and Health Products (Ansm) and network of Regional Centers, Pharmacovigilance - Website: www.ansm .sante.fr.
They are based on the antibacterial activity and pharmacokinetic characteristics of this drug. They take into account both the clinical studies to which it gave rise and its place in the range of antibacterial products currently available, and are limited to infections caused by organisms recognized as sensitive, The bacterial species responsible for infection may be multiple and / or resistant to the antibiotics currently available, and on this basis this drug is of particular interest in the following indications: acute otitis media in adults • acute maxillary sinusitis and other forms of sinusitis • superinfections of acute bronchitis of the at-risk patient, especially chronic ethyl, tobacco, elderly, over 65 years of age, Exacerbations of chronic bronchopneumopathies • Acute pneumonia of the at-risk patient, including chronic ethyl alcohol, tobacco, over 65 years of age or with swallowing disorders • Recurrent acute cystitis, uncomplicated cystitis Women and pyelonephritis, uncomplicated acute germs, sensitive, • high gynecological infections, in combination with another active antibiotic on Chlamydiae (see Warnings and Precautions for Use Precautions; • Periodontitis • Severe stomatal infections: abscesses, phlegmons, cellulites • Treatment of relay of the injectable route • Official recommendations regarding the appropriate use of antibacterials should be taken into account. >