Azivok

General characteristics. Structure:

Active ingredient: 262,03 mg of azithromycin of a dihydrate that is equivalent to 250 mg of azithromycin.

Excipients: lactose, starch corn, sodium lauryl sulfate, magnesium stearate.

Capsules firm gelatinous No. 0, case and lid: dye quinolinic yellow, dye a sunset yellow, titanium dioxide, gelatin, the water purified sodium lauryl sulfate, пропилпарагидроксибензоат (propylparaben), methylparahydroxybenzoate (methylparaben);

Ink black: (shellac, ethanol anhydrous, isopropanol, isobutanol, propylene glycol, ammonium sulfate strong solution, dye ferrous oxide black, sodium hydroxide, the water purified).

Antibacterial agent of a broad spectrum of activity, azalead, works bacteriostatically.

Pharmacological properties:

Pharmacodynamics. Azithromycin works on out of - and intracellular activators. 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, in high concentration renders bactericidal effect.

Are sensitive: aerobic gram-positive microorganisms: Streptococcus pneumoniae (penitsillinchuvstvitelny), Streptococcus pyogenes, Staphylococcus aureus (metitsillinchuvstvitelny); aerobic gram-negative microorganisms: Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, Haemophilus parainfluenzae, Pasteurella multocida, Neisseria gonorrhoeae; anaerobic microorganisms: Prevotella spp., Clostridium perfringens, Fusobacterium spp., Porphyromonas spp.; others - Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.

Are moderately sensitive or insensitive: aerobic gram-positive microorganisms – Streptococcus pneumoniae (moderately sensitive or resistant to penicillin).

Are steady: aerobic gram-positive microorganisms – Enterococcus faecalis, Staphylococcus spp., (metitsillinustoychivy); anaerobe bacterias – the Bacteroides fragilis group.

Streptococcus pneumoniae, beta and hemolitic Streptococcus spp. groups A, Enterococcus faecalis and Staphylococcus aureus (including metitsillinustoychivy strains), resistant to erythromycin and other macroleads, linkozamida, are steady also against azithromycin.

Pharmacokinetics. Absorption - high, кислотоустойчив, липофилен. Bioavailability after a single dose of 0.5 g - 37% (effect of "the first passing" through a liver), the maximum concentration after oral administration of 0.5 g - 0.4 mg/l, time of achievement of the maximum concentration - 2.5-2.9 h; in fabrics and cells concentration is 10-50 times higher, than in a blood plasma, distribution volume - 31.1 l/kg. Easily passes through gistogematichesky barriers. Well gets into respiratory tracts, urinogenital bodies and fabrics, including a prostate, into skin and soft tissues.

Gets through membranes of cells and creates high concentration in them, collects in lysosomes (that is especially important for an eradikation of intracellularly located activators). It is transported also by phagocytes: polymorphonuclear leukocytes and macrophages.

Concentration in the centers of an infection it is reliable above (for 24-34%), than in healthy fabrics, and correlates with expressiveness of inflammatory hypostasis. Remains in effective concentration within 5-7 days after reception of the last dose. Communication with proteins of plasma - 7-50% (it is inversely proportional concentration in blood).

In a liver it demetilirutsya, inactive metabolites are formed. Isoenzymes of CYP3A4, CYP3A5, CYP3A7 which inhibitor it is participate in metabolism of drug. Plasma clearance - 630 ml/min. The elimination half-life between 8 and 24 h after reception - 14-20 h, an elimination half-life in the range from 24 to 72 h - is removed with bile in not changed look, 6% 41 h 50% - kidneys.

Meal significantly changes pharmacokinetics: the maximum concentration and the area under a curve "concentration – time" (AUC) decreases by 52% and for 43% respectively.
At elderly men (65-85 years) pharmacokinetic parameters do not change, at women the maximum concentration increases (by 30-50%).

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to drug:

- upper respiratory tract infection and ENT organs (pharyngitis, tonsillitis, sinusitis, average otitis);

- lower respiratory tract infections (pneumonia (including caused by atypical activators), bronchitis);

- infections of skin and soft tissues (eels ordinary (the average Art. of weight), the ugly face, impetigo for the second time infected a dermatosis);

- infections of the urinogenital ways caused by Chlamydia trachomatis (an urethritis, a cervicitis);

- Lyme's disease (an initial stage - erythema migrans).

Route of administration and doses:

To adults and children 12 years with body weight more than 45 kg are more senior: inside, for 1 h to or in 2 h after food of 1 times a day; at infections of upper and lower respiratory tracts, ENT organs, skin and soft tissues – 0,5 g/days for 1 reception within 3 days (a course dose – 1,5 g); at eels ordinary – 0,5 g/days for 1 reception within 3 days, then on 0,5 g/days once a week during 9 weeks. Course dose of 6 g. The first weekly capsule should be accepted in 7 days after reception of the first daily capsule (8 day from an initiation of treatment), the subsequent 8 weekly capsules – at an interval of 7 days.

At infections of the urinogenital ways caused by Chlamydia trachomatis (an urethritis. a cervicitis) – once 1 g.

At Lyme's disease – for treatment of the I Art. (erythema migrans) – 1 g in the first day and 0,5 g daily from 2 to 5 day (a course dose – 3 g).

At use for patients with renal failures easy and moderate severity (KK more than 40 ml/min.) dose adjustment is not required; at use for patients with abnormal liver functions easy and moderate severity, dose adjustment is not required from elderly patients.

Features of use:

Use at pregnancy and in the period of a lactation. At pregnancy drug is used only if the estimated advantage for mother exceeds potential risk for a fruit.

In the period of a lactation for the period of treatment it is necessary to stop breastfeeding.

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 - with breaks at 24 o'clock.

Just as when performing any antibiotic treatment, at treatment by azithromycin, accession of superinfection is possible (including fungal).

Drug should be accepted, at least, in one hour prior to or in two hours after reception of antiacid drugs.

After cancellation of treatment of reaction of hypersensitivity at some patients can remain that demands specific therapy under observation of the doctor.

Azithromycin should be applied with care at patients with abnormal liver functions easy and moderate severity because of a possibility of development of fulminantny hepatitis and a heavy liver failure. In the presence of symptoms of dysfunction, such as quickly accruing adynamy, jaundice, urine darkening, tendency to bleedings, hepatic encephalopathy therapy by drug Azivok it is necessary to stop and conduct a research of a functional condition of a liver.

At patients with renal failures easy and moderate severity (KK more than 40 ml/min.) therapy by drug Azivok should be carried out with care under control of a condition of functions of kidneys.

At long reception of azithromycin development of the pseudomembranous colitis caused by Clostridium difficile as in the form of slight diarrhea, and heavy colitis is possible. At development of diarrhea against the background of azithromycin reception, and also in 2 months after the end of therapy it is necessary to exclude klostridialny pseudomembranous colitis. The drugs braking an intestines peristaltics are contraindicated.

Drug should not be used longer courses, than it is specified in the instruction as pharmacokinetic properties of azithromycin allow to recommend the short and simple mode of dosing. Use of drug can provoke development of a myasthenic syndrome or cause a myasthenia aggravation.

Influence on ability to manage motor transport and mechanisms. Considering side effects of drug from the central nervous system, it is necessary to be careful during the driving of motor transport and work with the mechanisms demanding concentration of attention.

Side effects:

From circulatory system: thrombocytopenia, neutropenia, hemolitic anemia.

From a nervous system: dizziness / вертиго, headache, spasms, drowsiness, paresthesia, adynamy, sleeplessness, hyperactivity, aggression, concern, nervousness, agitation, nonsense, hallucinations, gipestenziya, alarm, syncope, loss of sense of smell, loss of flavoring feelings, perversion of sense of smell, myasthenia.

From sense bodys: a sonitus, a reversible hearing disorder up to deafness (at reception of high doses for a long time), disturbance of perception of taste and a smell, a vision disorder.

From cardiovascular system: a heart consciousness, arrhythmia like "pirouette", lowering of arterial pressure, ventricular tachycardia, increase in an interval of QT, bidirectional ventricular tachycardia, "inflows" of blood to persons.

From the alimentary system: gastritis, abdominal distention, pancreatitis, nausea, vomiting, diarrhea, abdominal pains / spasms, a meteorism, an eructation, a digestive disturbance, anorexia, a lock, language discoloration, pseudomembranous colitis, cholestatic jaundice, fulminantny hepatitis, an abnormal liver function, a liver failure, a liver necrosis (it is possible from the death), a gastroenteritis, a dysphagy, dryness of a mucous membrane of an oral cavity, an ulcer of a mucous membrane of an oral cavity, increase in secretion of sialadens.

Allergic reactions: an itch, skin rashes, a Quincke's disease, a small tortoiseshell, an eosinophilia, anaphylactic reaction, including a Quincke's edema (in rare instances from the death), a mnogoformny erythema, Stephens-Johnson's syndrome, a Lyell's disease, hypersensitivity reaction.

From a musculoskeletal system: arthralgia, osteoarthritis, mialgiya, dorsodynia, neck pain.

From urinogenital system: intersticial nephrite, an acute renal failure, pain in kidneys, a metrorrhagia, dysfunction of testicles, a dysuria.

From respiratory system: pneumonia, pharyngitis, raspiratorny diseases, rhinitis, short wind, nasal bleeding.

From integuments: dermatitis, xeroderma, perspiration.

Others: vaginitis, candidiasis, photosensitization, indisposition, feeling of fatigue, stethalgia, peripheral hypostases, face edema, fever.

Laboratory indicators: decrease in quantity of lymphocytes, increase in activity of aspartate aminotransferase, alaninaminotranspherase;

in a blood plasma: increase in quantity of basophiles, monocytes, neutrophils, decrease or increase in concentration of bicarbonates, increase in activity of an alkaline phosphatase, increase in content of chlorine, increase in concentration of glucose, increase in quantity of thrombocytes, increase in a hematocrit, change of content of sodium, increase in concentration of bilirubin, increase in concentration of urea, change of content of potassium.

Interaction with other medicines:

- Antiacid means do not influence bioavailability of azithromycin, but reduce the maximum concentration in blood by 30% therefore drug should be accepted in one hour prior to or in two hours after reception of these drugs and food.

- Azithromycin does not influence concentration of carbamazepine, a didanozin, rifabutin and Methylprednisolonum in blood at combined use.

- In pharmacokinetic researches of influence of a single dose of Cimetidinum on pharmacokinetics of azithromycin changes of pharmacokinetics of azithromycin, on condition of use of Cimetidinum in 2 hours prior to azithromycin are not revealed.

- Simultaneous use of azithromycin (600 mg/days once) and an efavirenza (400 mg/days) daily within 7 days did not cause what – or clinically significant pharmacokinetic interaction.

- Simultaneous use of azithromycin (1200 mg once) did not change pharmacokinetics of a flukonazol (800 mg once). The general exposure and an elimination half-life of azithromycin did not change at simultaneous use of a flukonazol, however at the same time observed decrease in Cmax of azithromycin (for 18%) that had no clinical value.

- Simultaneous use of azithromycin (1200 mg once) did not cause statistically reliable influence on pharmacokinetics of an indinavir (on 800 mg three times a day within 5 days).

- Simultaneous use within 5 days for healthy volunteers of azithromycin with tsetiriziny (20 mg) did not lead to pharmacokinetic interaction and essential change of an interval of QT.

- At use for healthy volunteers the evidence of influence of azithromycin (500 mg/days daily within 3 days) on AUC and Cmax of a sildenafil or its main circulating metabolite is not obtained.

- Azithromycin does not influence bioavailability of co-trimoxazole.

- Considerable changes of pharmacokinetic indicators at simultaneous use of azithromycin with triazolamy or midazolam in therapeutic doses are not revealed.

At simultaneous use of azithromycin and a rifabutin the neutropenia was sometimes observed in spite of the fact that the neutropenia was associated using a rifabutin, relationship of cause and effect between use of a combination of azithromycin and a rifabutin and a neutropenia is not established.

- Azithromycin does not influence theophylline pharmacokinetics, however, at joint reception with other macroleads concentration of theophylline in a blood plasma can increase.

- In need of combined use with cyclosporine, it is recommended to control concentration of cyclosporine in a blood plasma and to respectively adjust a dose.

- At joint reception of digoxin and azithromycin it is necessary to control concentration of digoxin in blood since simultaneous use of makrolidny antibiotics, including azithromycin, with R-glycoprotein substrates, such as digoxin, leads to increase in concentration of substrate of the R-glycoprotein in a blood plasma.

- In need of joint reception with warfarin it is recommended to carry out careful control of a prothrombin time.

- It was established that the concomitant use of a terfenadin and antibiotics of a class of macroleads causes arrhythmia and lengthening of QT of an interval. Proceeding from it, it is impossible to exclude the above-stated complications at a joint priyemeneniye of a terfenadin and azithromycin.

- As there is a possibility of inhibition of an isoenzyme of CYP3A4 azithromycin in a parenteral form at combined use with cyclosporine, terfenadiny, ergot alkaloids, tsizapridy, Pimozidum, quinidine, astemizoly and other drugs which metabolism happens to participation of this enzyme it is necessary to consider a possibility of such interaction at purpose of azithromycin for intake.

- Considering theoretical possibility of an ergotism, simultaneous use of azithromycin with derivatives of alkaloids of an ergot (ergotamine, and dihydroergotamine) it is not recommended.

- At simultaneous use with a zidovudine azithromycin exerts insignificant impact on pharmacokinetics, including removal by kidneys, a zidovudine or its glyukuronidny metabolite.

- Azithromycin poorly interacts with P450 cytochrome isoenzymes, is not revealed that azithromycin participates in pharmacokinetic interactions similar to erythromycin and other macroleads, azithromycin is not the inductor and inhibitor of isoenzymes of P450 cytochrome.

- Simultaneous use of azithromycin (1200 mg) and a nelfinavira (on 750 mg 3 times a day) causes increase in equilibrium concentration of azithromycin in a blood plasma, clinically significant side effects were not observed also dose adjustments of azithromycin at its simultaneous use with nelfinaviry it is not required.

- Separate messages on cases of a rabdomioliz at the patients who are at the same time accepting azithromycin and statines were received.

Contraindications:

Hypersensitivity (including to erythromycin; to ketoleads and other macroleads, to azithromycin, other components of drug), a heavy liver failure (a class C on Chayld-Pyyu); a heavy renal failure (the clearance of creatinine (CC) less than 40 ml/min.), a concomitant use of ergotamine and dihydroergotamine, the lactation period, children's age (up to 12 years with body weight less than 45 kg, for this dosage form), a lactose intolerance, insufficiency of lactase, glyukozo-galaktozny malabsorption (since lactose is a part of drug).

With care. Abnormal liver functions easy and moderate severity, a renal failure of easy and average degree of severity (KK more than 40 ml/min.), at patients with existence of proaritmogenny factors (especially at elderly patients): with inborn or acquired by lengthening of an interval by QT, at the patients receiving therapy by antiarrhytmic drugs of the classes IA (quinidine, procaineamide), III (дофетилид, Amiodaronum and соталол), tsizapridy, terfenadiny, antipsychotic drugs (Pimozidum), antidepressants (tsitalopra), ftorkhinolinam (moxifloxacin and levofloxacin), with disturbances of water and electrolytic balance, especially in case of a hypopotassemia or a hypomagnesiemia, with clinically significant bradycardia, arrhythmia of heart or heavy heart failure; simultaneous use of digoxin, warfarin, cyclosporine, for patients with a myasthenia and during pregnancy.

Overdose:

Symptoms: severe nausea, temporary hearing loss, vomiting, diarrhea.

Treatment: a gastric lavage, symptomatic therapy, a hemodialysis it is not effective.

Storage conditions:

In the place protected from light, at a temperature not above 30 °C. To store in the place, unavailable to children. A period of validity - 3 years. Not to use after expiry date.

Issue conditions:

According to the recipe

Packaging:

Capsules of 250 mg. On 6 capsules in алюм / PVC the blister, on 1 blister together with the application instruction in a cardboard pack.