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

They are limited to infections due to germs, defined as sensitive

· Documented streptococcal A, beta-hemolytic angina, as an alternative to treatment with beta-lactams, especially when it can not be used >
· Superinfections of bronchitis, acute

· Exacerbations of chronic bronchitis

· Stomatological infections.

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

Adult

· Angina, stomatological infections: 500 mg (2 tablets) daily for 3 days
This dosage, with a short administration time of 3 days, is explained by the special pharmacokinetic properties of azithromycin and the maintenance of activity in these indications for several days after the last dose.

· Superinfections of acute bronchitis, exacerbations of chronic bronchitis: 500 mg (2 tablets) on the first day, then 250 mg (1 tablet) the following 4 days. The processing time will be 5 days.

· No dosage modification in the subject, aged

· Same dosage in patients with moderate to severe hepatic impairment (see section 4.4),
Mode of administration

The tablets may be taken either during or outside meals, in a single, daily dose.


(J: Anti-infectives)

Antibiotic of the family of macrolides.

Azithromycin is the first molecule of the class of azalide antibiotics (macrolide family).

Azithromycin acts by inhibiting the synthesis of bacterial proteins by binding to the 50S portion of the ribosome and preventing peptide translocation.


Critical concentrations separate sensitive strains from intermediate sensitivity strains and resistant strains

S mg / l, and R> 4; 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

Bacillus cereus

Corynebacterium diphtheriae

Enterococci

50 - 70%

Rhodococcus equi

Staphylococcus méti-S

Staphylococcus meti-R; *

70 - 80%

Streptococcus B

Streptococcus non; groupable

30 - 40%

Streptococcus pneumoniae

35 - 70%

Streptococcus pyogenes

16 - 31%

Gram-negative Aerobes

Bordetella pertussis

Branhamella catarrhalis

Campylobacter

Legionella

Moraxella

Anaerobes

Actinomyces

Bacteroides

30 - 60%

Eubacterium

Mobiluncus

Peptostreptococcus

30 - 40%

Porphyromonas

Prevotella

Propionibacterium acnes

Categories

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

Other

Borrelia, burgdorferi

Chlamydia

Coxiella

Leptospires
Mycoplasma pneumoniae

Treponema pallidum

MODERATELY SENSITIVE SPECIES

(In vitro sensitivity, intermediate)

Gram-negative Aerobes

Haemophilus

Neisseria gonorrhoeae

Anaerobes

Clostridium perfringens

Other

Ureaplasma urealyticum

RESISTANT SPECIES

Gram-positive aerobes

Corynebacterium jeikeium

Nocardia, asteroids

Gram-negative Aerobes

Acinetobacter

Enterobacteria

Pseudomonas

Anaerobes

Fusobacterium

Other

Mycoplasma hominis

* 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 MUST NEVER BE USED in case of

· A history of allergic reaction to azithromycin, erythromycin, any other macrolide or any of the excipients

· Combination with ergot alkaloids, dihydroergotamine, ergotamine (see sections 4.4, 4.4, 4.4 and 4.4)

· Association with cisapride (see section Interactions with other medicinal products and other forms of interaction)

· Association with colchicine (see section Interactions with other medicinal products and other forms of interaction)

· Severe hepatic impairment (see Warnings and Precautions) ·

As with erythromycin and other macrolides, rare, severe allergic reactions such as edema, angioedema and anaphylactic (rarely fatal) reactions have been reported. The possibility of a recurrence of symptoms after discontinuation of symptomatic treatment requires the prolongation of surveillance and possible treatment.
As the main route of elimination of azithromycin, the prescription of azithromycin is not recommended in patients with severe hepatic insufficiency or in patients with severe cholestasis. Fulminant hepatitis, which may lead to life-threatening hepatic impairment, have been reported with azithromycin (see section 4.4) .Some patients may have had a pre-existing or pre- Other medicines, hepatotoxic drugs

Hepatic function tests should be performed in the presence of signs or symptoms of impairment, liver function such as development, rapid asthenia associated with jaundice, dark urine , Bleeding or hepatic encephalopathy. The use of azithromycin should be discontinued if liver dysfunction occurs.

In the case of treatment with ergot derivatives, certain antibiotics, macrolides administered concomitantly, precipitated ergotism. There is no data for a possible interaction between rye ergot and azithromycin. However, taking into account the theoretical risk of ergotism, derivatives of ergot, rye and azithromycin should not be administered jointly.

As with all antibiotics, monitoring of signs of superinfection by non-susceptible organisms, including fungi, is recommended.

Cases of diarrhea associated with Clostridium difficile are reported with the use of many antibiotics, including azithromycin. The severity of these diarrhea can lead to life-threatening pseudomembranous colitis.

It is important that this diagnosis is referred to in patients with diarrhea during or after an antibiotic, as cases have been observed up to 2 months after discontinuation of treatment. Br>

In patients with renal insufficiency, severe (glomerular filtration rate 40 ml / min). In patients with creatinine clearance, less than 40 ml / min, azithromycin should be prescribed.

Cases of prolongation of cardiac repolarization and prolongation of the QT interval, involving a risk of cardiac arrhythmia and torsades de pointes, were observed during treatment with other macrolides

A similar effect can not be totally ruled out with azithromycin in patients with an increased risk of prolonging cardiac repolarization (see section 4.4), therefore caution should be exercised when treating Patients

· Constrained or congenital prolongation of the QT interval

· Currently receiving treatment with other active substances known to prolong the QT interval such as Class IA and III antiarrhythmics, cisapride and terfenadine.

· Presenting an electrolytic disorder, in particular, in cases of hypokalemia and hypomagnesemia

· Presenting bradycardia, cardiac arrhythmia, or severe heart failure.

Exacerbations of symptoms of myasthenia gravis and new outbreaks of myasthenic syndrome have been reported in patients on azithromycin (see section Effects, undesirable). Code>
Associations, contraindicated

+; Cisapride

Increased risk of rhythm disorders, including ventricular torsades de pointes

+; Colchicine

Increased adverse effects of colchicine to potentially fatal consequences

+; Dihydroergotamine

Ergotism with possibility of end-necrosis (inhibition of hepatic elimination of ergot alkaloids)

+; Ergotamine

Ergotism with possibility of end-necrosis (decreased hepatic elimination of ergotamine alkaloids)

Associations, deprecated

+ Dopaminergic ergot alkaloids

(Bromocriptine, cabergoline, lisuride, pergolide)

Increase in plasma dopaminergic concentrations with possible increase in activity or signs of overdose

Associations subject to precautions for use

+; Atorvastatin

Increased risk of adverse effects (concentration-dependent) to type, rhabdomyolysis, decreased metabolism, liver of cholesterol-lowering drug
Use lower doses, cholesterol-lowering or other statin not affected by this type of interaction

+; Ciclosporin

Risk of increased concentrations of ciclosporin and creatinine in blood

Determination of blood concentrations of ciclosporin, control of renal function and dosage adjustment during and after association of macrolide

+ Digoxine

Elevation of digoxinemia by increased absorption of digoxin

Clinical monitoring and, if appropriate, digoxinemia during treatment with azithromycin and after its discontinuation

+ Drugs capable of giving torsades of points

Increased risk of rhythm disorders, including ventricular torsades de pointes

Clinical and electrocardiographic monitoring during association.

+; Simvastatin

Increased risk of adverse effects (concentration-dependent) to type, rhabdomyolysis, decreased metabolism, liver of cholesterol-lowering drug
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.

There is no data on this subject.

Conduct: gastric lavage, and symptomatic treatment

Pregnancy

1st quarter

It is preferable, as a precautionary measure, not to use azithromycin during the first trimester of pregnancy. Indeed, although the animal data in the rodent do not show any malformative effect, the clinical data are insufficient.
From the 2 nd quarter

Due to the expected benefit, the use of azithromycin may be considered from the 2 nd quarter of pregnancy if needed. In fact, although limited, the clinical data are reassuring in case of use beyond the first trimester.

Breastfeeding

No data on passage in breast milk

The safety of azithromycin in lactating women has not been established and the prescription shall be carried out only if the expected benefits appear to be greater than the risks involved.
< Br>
· Mucocutaneous and allergic: rash, photosensitivity, arthralgia, urticaria, pruritus, rarely, angioedema, anaphylactic reactions. Rare cases of severe skin reactions have been reported.
Gastrointestinal: nausea, vomiting, dyspepsia, diarrhea (rarely severe), abdominal pain, pancreatitis. Rare cases of colitis, pseudomembranous have been reported.

· Hepatic: increased enzymes, reversible liver disease at cessation of treatment, rare cases of hepatic necrosis and insufficiency, liver rarely involved in prognosis, vital. Isolated cases of cholestatic hepatitis have been reported

· Neurological: dizzy sensations, rare cases of convulsions have been reported.

· Hematologic: isolated cases of thrombocytopenia have been reported.

· Psychiatric: rare cases of aggressive behavior, nervousness, agitation and anxiety have been reported.

· Genitals: vaginitis.

· Hearing: rare cases of hearing disorders with, tinnitus or deafness have been reported.

· General: Candidiasis

Reporting of suspected adverse reactions

The reporting of suspected adverse effects after authorization of the drug is important. It provides continuous monitoring of the benefit / risk ratio of the drug. Health professionals report any suspected adverse reactions via the national reporting system: National Agency for the Safety of Medicines and Health Products (Ansm) and network of Regional Pharmacovigilance Centers -
They are based on the antibacterial activity and pharmacokinetic characteristics of azithromycin. They take into account both the clinical studies to which this drug has given rise and its place in the range of antibacterial products currently available, are limited to infections due to germs, defined as sensitive, documented angina Beta-hemolytic streptococcus as an alternative to treatment with beta-lactam antibiotics, especially when beta-lactam antibiotics can be used, • superinfections of bronchitis, acute, • exacerbations of chronic bronchitis, • stomatological infections. Official recommendations concerning the appropriate use of antibacterials should be taken into account.