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 the germs defined as
· Documented streptococcal A, beta-hemolytic angina, as an alternative to treatment, by beta-lactam antibiotics, especially when it can not be used. >
· Superinfections of acute bronchitis
· Exacerbations of chronic bronchitis
· Stomatological infections.
Official recommendations concerning the appropriate use of antibacterials should be taken into account.
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) first, 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 insufficiency (see section 4.4)
Administration mode
The tablets may be taken on or off meals in a single daily dose.
ATC code J01FA10.
(J: Anti-infectives)
Antibiotic of the family 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 strains of intermediate sensitivity and the latter from resistant strains
S, £ 0.5, 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 prevalence of resistance in France is known for a bacterial species, it is indicated in the table below
Categories
Frequency of resistance acquired in France (> 10%) (values, extremes)
SPECIES, SENSITIVE
Gram aerobics, positive
Bacillus, cereus
Corynebacterium, diphtheriae
Enterococci
50 - 70%
Rhodococcus equi
Staphylococcus, metti-S
Staphylococcus, meti-R *
70 - 80%
Streptococcus, B
Streptococcus, non-groupable
30 - 40%
Streptococcus pneumoniae
35 - 70%
Streptococcus, pyogenes
16-31%
Gram aerobics, negative
Bordetella; pertussis
Branhamella catarrhalis
Campylobacter
Legionella
Moraxella
Anaerobes
Actinomyces
Bacteroides
30 - 60%
Eubacterium
Mobiluncus
Peptostreptococcus
30 - 40%
Porphyromonas
Prevotella
Propionibacterium, acnes
Other
Borrelia, burgdorferi
Chlamydia
Coxiella
Leptospires
Mycoplasma pneumoniae
Treponema pallidum
SPECIES, MODERATELY SENSITIVE
(In vitro of intermediate sensitivity)
Gram aerobics, negative
Haemophilus
Neisseria, gonorrhoeae
Anaerobes
Clostridium, perfringens
Other
Ureaplasma; urealyticum
SPECIES, RESISTANTS
Gram aerobics, positive
Corynebacterium, jeikeium
Nocardia, asteroids
Gram aerobics, negative
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) ·
This drug is contraindicated in patients with allergy to wheat (other than celiac disease).
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, has been reported with azithromycin (see section 4.4). Some patients may have had liver disease, pre-existing or other 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>
Related to excipients
This medicinal product may be administered in the case of celiac disease. Wheat starch may contain gluten, but only in the trace state, and is therefore considered to be safe for persons with celiac disease.
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.
Without object.
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
Absence of data on passage through 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 rarely life-threatening hepatic impairment. However, no causal link could be established.
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
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, and are limited to infections due to the germs defined as sensitive, Documented streptococcus A, beta-hemolytic, as an alternative to treatment, by beta-lactam antibiotics, especially when beta-lactam antibiotics can not be used • superinfections of acute bronchitis • exacerbations of chronic bronchitis • stomatological infections. The official recommendations concerning the appropriate use of antibacterials should be taken into account.