Producer: JSC Pharmstandart Russia
Code of automatic telephone exchange: J01FA10
Release form: Firm dosage forms. Capsules.
General characteristics. Structure:
Active agent: azithromycin a dihydrate in terms of azithromycin – 250 mg.
Excipients: Mannitolum (mannitol) – 54,58 mg, starch corn – 13,10 mg, magnesium stearate – 2,0 mg, sodium lauryl sulfate – 0,32 mg;
Gelatinous solid capsules
structure of the capsule: the case and a lid – titanium dioxide (Е 171), gelatin (gelatin medical).
Description: capsules of white color No. 0. Contents of capsules – powder of color, white or white with a yellowish shade.
Pharmacodynamics. Antibiotic of a broad spectrum of activity. Is the representative of subgroup of makrolidny antibiotics – azaleads. Communicating with 50S in subunit of ribosomes, oppresses to a peptidtranslokaz at a broadcasting stage, suppresses protein synthesis, slows down growth and reproduction of bacteria, works bacteriostatically, in high concentration renders bactericidal effect. Works on out of - and intracellular activators.
It is active concerning gram-positive aerobic microorganisms: Streptococcus spp. (A, B, C groups, G), Streptococcus pneumoniae (penitsillinchuvstvitelny), Streptococcus pyogenes, Staphylococcus aureus (metitsillinchuvstvitelny); gram-negative aerobic microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Legionella pneumophila, Neisseria gonorrhoeae, Pasteurella multocida; some anaerobic microorganisms: Prevotella spp., Clostridium perfringens, Fusobacterium spp., Porphyriomonas spp.; and also Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.
The microorganisms capable to develop azithromycin resistance: gram-positive aerobes (Streptococcus pneumoniae (penitsillinustoychivy)). Initially steady microorganisms: gram-positive aerobes (Enterococcus faecalis, Staphylococcus spp. (metitsillinustoychivy staphylococcus show very high degree of resistance to macroleads), the gram-positive bacteria steady against erythromycin); anaerobe bacterias (Bacteroides fragilis).
Pharmacokinetics. Azithromycin is quickly soaked up from digestive tract that is caused by its stability in acid medium and lipophilicity. After intake of 500 mg the maximum concentration of azithromycin in a blood plasma is reached in 2,5-3,0 h and makes 0,4 mg/l. Bioavailability makes 37%.
Azithromycin well gets into respiratory tracts, bodies and fabrics of an urogenital path (in particular in a prostate), in skin and soft tissues. High concentration in fabrics (is 10-50 times higher, than in a blood plasma) and a long elimination half-life are caused by low linkng of azithromycin with proteins of a blood plasma, and also its ability to get into eukaryotic cells and to concentrate in the environment with a low rn, a surrounding lysosome. It, in turn, determines the large seeming distribution volume (31,1 l/kg) and high plasma clearance. Ability of azithromycin to collect preferential in lysosomes is especially important for elimination of intracellular activators. It is proved that phagocytes deliver azithromycin to places of localization of an infection where it is released in the course of phagocytosis. Concentration of azithromycin in the centers of an infection it is reliable above, than in healthy fabrics (on average for 24-34%) and correlates with degree of inflammatory hypostasis. Despite high concentration in phagocytes, azithromycin has no significant effect on their function.
Azithromycin remains in bactericidal concentration in the inflammation center within 5-7 days after reception of the last dose that allowed to develop short (3-day and 5-day) courses of treatment.
In a liver it demetilirutsya, the formed metabolites are not active.
Removal of azithromycin from a blood plasma takes place in 2 stages: the elimination half-life makes 14-20 h in the range from 8 to 24 h after administration of drug and 41 h – in the range from 24 to 72 h that allows to use drug of 1 times/days.
Azithromycin is removed, generally in not changed look – 50% by intestines, 12% kidneys.
Indications to use:
The infectious and inflammatory diseases caused by microorganisms, sensitive to drug, including:
· upper respiratory tract infection and ENT organs (quinsy, sinusitis, tonsillitis, pharyngitis, average otitis);
· lower respiratory tract infections (the pneumonia including caused by atypical activators; bronchitis, including acute, aggravation of chronic);
· infections of an urogenital path (urethritis, cervicitis);
· infections of skin and soft tissues (Lyme's disease (an initial stage – erythema migrans), an ugly face, impetigo, secondary pyodermatoses, eels ordinary (acnes) of moderate severity).
Route of administration and doses:
Inside, for 1 h to or in 2 h after food of 1 times a day.
The adult at infections of upper and lower respiratory tracts, ENT organs, skin and soft tissues (except for an initial stage of a disease of Lyme (erythema migrans) and an acne of moderate severity) – 500 mg (2 capsules) a day for 1 reception within 3 days (a course dose – 1,5 g).
At an initial stage of a disease of Lyme (erythema migrans) – 1000 mg (4 capsules) a day in the first day at one time, further on 500 mg (2 capsules) a day daily from 2 to 5 day (a course dose – 3 g).
At the indication eels accept ordinary (acnes) of moderate severity in the 1, 2 and 3 day of treatment on 500 mg (2 capsules) once a day, then do a break from the fourth to the seventh day, from the eighth day of treatment accept 500 mg (2 capsules) within 9 weeks (a course dose of 6 g) once a week.
At infections of an urogenital path (an urethritis, a cervicitis) for treatment of an uncomplicated urethritis or a cervicitis trample down once 1 g (4 capsules).
To children with the body weight from 25 to 45 kg at infections of upper and lower respiratory tracts, ENT organs, skin and soft tissues – 250 mg/days within 3 days; at treatment of an initial stage of a disease of Lyme (erythema migrans) – 500 mg (2 capsules) in the first day and 250 mg daily from 2 to 5 day (a course dose – 1,5 g).
To children with body weight more than 45 kg at infections of upper and lower respiratory tracts, ENT organs, skin and soft tissues – 500 mg (2 capsules) a day for 1 reception within 3 days; at treatment of an initial stage of a disease of Lyme (erythema migrans) – 1000 mg (4 capsules) in the first day and 500 mg (2 capsules) daily from 2 to 5 day (a course dose – 3 g).
Features of use:
In case of the admission of reception of one dose of drug it is necessary to accept the passed dose as soon as possible, and the subsequent – bucketed in 24 h. Azithromycin should be accepted at least in 1 hour prior to or in 2 hours after reception of antiacid medicines.
Azithromycin should be applied with care to patients with a moderate abnormal liver function because of a possibility of development of fulminantny hepatitis and a heavy liver failure at such patients. In the presence of symptoms of an abnormal liver function (quickly accruing adynamy, jaundice, darkening of color of urine, tendency to bleedings, hepatic encephalopathy) therapy by azithromycin it is necessary to stop and conduct a research of a functional condition of a liver.
At a moderate renal failure (KK more than 40 ml/min.) use of azithromycin should be carried out under control of function of kidneys.
The concomitant use of azithromycin with derivatives of ergotamine and dihydroergotamine because of possible development of an ergotism is contraindicated.
At drug use, both against the background of reception, and in 2-3 weeks after the termination of treatment development of the diarrhea caused by Clostridium difficile (psevdomemranozny colitis) is possible. In mild cases there is enough cancellation of treatment and use of ion-exchange resins (Colestyraminum, колестипол), in hard cases compensation of loss of liquid, electrolytes and protein, purpose of Vancomycinum, bacitracin or metronidazole is shown. It is impossible to apply the medicines braking an intestines peristaltics.
As lengthening of an interval of Q-T at the patients receiving macroleads including azithromycin is possible, at use of azithromycin it is necessary to be careful at patients with the known risk factors of lengthening of an interval of Q-T: advanced age; disturbance of electrolytic balance (hypopotassemia, hypomagnesiemia); syndrome of inborn lengthening of an interval of Q-T; heart diseases (heart failure, myocardial infarction, bradycardia); a concomitant use of the medicines capable to extend Q-T interval (including antiarrhytmic means of IA and the III classes, tricyclic and tetracyclic antidepressants, neuroleptics, ftorkhinolona).
Azithromycin can provoke development of a myasthenic syndrome or cause a myasthenia aggravation гравис.
The European department of WHO recommends azithromycin as choice drug at treatment of a chlamydial infection at pregnant women. Azithromycin on risk of use for pregnant women, according to FDA classification, belongs to the category B (reproduction researches on animals did not reveal damage of a fruit owing to azithromycin reception, but controlled researches at pregnant women were not conducted).
Influence on ability to manage vehicles, mechanisms
At emergence of side reactions from TsNS patients are recommended to refrain from control of motor transport and occupations other potentially dangerous types of activity demanding the increased concentration of attention, speed of psychomotor and motor reactions.
The majority of noted side reactions are reversible after the termination of a course of treatment or drug withdrawal.
Classification of frequency of development of side effects (WHO): very often (with a frequency more than 1/10), it is frequent (with a frequency not less than 1/100, but less than 1/10), infrequently (with a frequency not less than 1/1000, but less than 1/100), is rare (with a frequency not less than 1/10000, but less than 1/1000), is very rare (with a frequency less than 1/10000), (including separate messages).
From TsNS: often – dizziness, a headache, paresthesia, disturbance of perception of flavoring feelings, anorexia; infrequently – uneasiness, nervousness, a giposteziya, sleeplessness, drowsiness; seldom – agitation; very seldom – faints, spasms, a psychomotor hyperactivity, an anosmia, loss of flavoring feelings, a parosmiya, a myasthenia aggravation гравис.
From sense bodys: infrequently – decrease in auditory acuity, a sonitus; seldom – вертиго, decrease in visual acuity, deafness.
From cardiovascular system: infrequently – a heart consciousness; seldom – a lowering of arterial pressure; very seldom – arrhythmia, including: ventricular tachycardia, increase in an interval of Q-T, arrhythmia like "pirouette".
From the alimentary system: very often – nausea, diarrhea, an abdominal pain, a meteorism; often – vomiting; infrequently – gastritis, a lock, a melena; very seldom – language discoloration, pseudomembranous colitis, pancreatitis.
From a liver and biliary tract: infrequently – hepatitis, a hyperbilirubinemia, increase in activity of "hepatic" transaminases; very seldom – cholestatic jaundice, a liver failure (in rare instances with a lethal outcome, generally against the background of an abnormal liver function), fulminantny hepatitis, a liver necrosis.
Allergic reactions: often – an itch, rash; not often – Stephens-Johnson's syndrome, a photosensitization, a small tortoiseshell; very seldom – anaphylactic reactions (including a Quincke's disease) in rare instances from the death, a toxic epidermal necrolysis, a multiformny erythema.
From a musculoskeletal system: often – an arthralgia.
Infections and invasions: infrequently – a vaginitis, candidiasis of various localizations.
It is necessary to report about emergence of any side effect to the attending physician.
Interaction with other medicines:
Antiacid means (aluminum and magniysoderzhashchy) do not influence bioavailability of azithromycin, but reduce its maximum concentration in blood by 30% therefore the interval between their reception has to make at least 1 hour to or 2 hours after reception of the specified drugs. At a concomitant use with derivatives of ergotamine and dihydroergotamine strengthening of their toxic action (a vasospasm, a dizesteziya) is possible.
At combined use with anticoagulants of indirect action of a coumarinic row (warfarin) and azithromycin (in usual doses) careful control of a prothrombin time is necessary for patients.
It is necessary to be careful at joint purpose of a terfenadin and azithromycin as it was established that the concomitant use of a terfenadin and macroleads can cause arrhythmia and lengthening of Q-T of an interval. Proceeding from it, it is impossible to exclude the above-stated complications at joint reception of a terfenadin and azithromycin.
At simultaneous use with cyclosporine, it is necessary to control concentration of cyclosporine in blood.
At joint reception of digoxin and azithromycin it is necessary to control concentration of digoxin in blood as many macroleads increase absorption of digoxin in intestines.
At simultaneous use with nelfinaviry increase in frequency of side reactions of azithromycin (decrease in hearing, increase in activity of "hepatic" transaminases) is possible.
At joint reception of azithromycin and a zidovudine, azithromycin does not influence pharmacokinetic parameters of a zidovudine in a blood plasma or on removal by kidneys of its and its metabolite of a glucuronide, but concentration of an active metabolite – a fosforilirovanny zidovudine in mononuclear cells of peripheral blood increases. Clinical value of this fact is not defined.
At a concomitant use of azithromycin and a rifabutin development of a neutropenia which development mechanism, and also existence of relationship of cause and effect with administration of drug are not established is in rare instances possible.
At a concomitant use флуконазол reduces Cmax of azithromycin by 18%.
Azithromycin does not influence concentration of carbamazepine, Cimetidinum, didanozin, efavirenz, flukonazol, indinavir, midazolam, theophylline, a triazolam, Trimethoprimum/sulfamethoxazole, a tsetirizin, sildenafil, atorvastatin, rifabutin and Methylprednisolonum in blood at simultaneous use.
It is necessary to consider a possibility of inhibition of an isoenzyme of CYP3A4 drugs of group of macroleads at simultaneous use with cyclosporine, terfenadiny, ergot alkaloids, tsizapridy, Pimozidum, quinidine, astemizoly and other medicines which metabolism happens to participation of this enzyme, however, at use of azithromycin of such type of interaction it was not noted.
Hypersensitivity to azithromycin (including to other macroleads), to drug components; heavy liver failure: more than 9 points on a scale of Chayld-Pyyu (there are no data on efficiency and safety); heavy renal failure: the clearance of creatinine (CC) less than 40 ml/min. (there are no data on efficiency and safety); children aged up to 12 years with body weight less than 25 kg (for this dosage form); concomitant use of ergotamine and dihydroergotamine.
At a moderate abnormal liver function (7-9 points on a scale of Chayld-Pyyu); chronic renal failure (KK more than 40 ml/min.); arrhythmias or predisposition to arrhythmia and lengthening of an interval of Q-T; at a concomitant use of a terfenadin, warfarin, digoxin; at a myasthenia; at pregnancy.
Use during pregnancy and during breastfeeding
Use of drug during pregnancy is possible only in that case when the estimated advantage for mother exceeds potential risk for a fruit.
Descriptions of separate cases and observation researches showed that use of azithromycin during pregnancy does not lead to increase in frequency of failures of pregnancy and is not connected with developing of any specific malformations at the child.
In need of purpose of drug in the period of a lactation it is necessary to stop breastfeeding.
At reception of high doses of drug strengthening of side effect can be observed: temporary hearing loss, severe nausea, vomiting, diarrhea. In this case the gastric lavage, purpose of absorbent carbon, performing symptomatic therapy is shown.
To store at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 3 years. Not to use after the period of validity specified on packaging.
According to the recipe
Capsules of 250 mg. 6 or 10 capsules in a blister strip packaging. 1, 2, 6 or 12 blister strip packagings with the application instruction in a pack from a cardboard.