Active substanceAzithromycinAzithromycin
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  • Dosage form: & nbspfilm coated tablets
    Composition:

    Each film-coated tablet contains:

    Name

    Amount (mg)

    Active substance:

    Azithromycin dihydrate

    in terms of azithromycin

    262,02

    250,00

    524,04

    500,00

    Excipients:

    Calcium dihydrogen phosphate

    96,73

    193,46

    Croscarmellose sodium

    25,00

    50,00

    Pregelatinized starch

    45,00

    90,00

    Hypromellose

    13,50

    27,00

    Sodium lauryl sulfate

    0,75

    1,5

    Magnesium stearate

    7,00

    14,00

    Film sheath (Opadrai II white 31K58902):

    Lactose Monohydrate

    5,40

    10,80

    Hypromellose

    3,78

    7,56

    Titanium dioxide

    3,24

    6,48

    Triacetin

    1,08

    2,16

    Description:

    250 mg tablets: Oval, biconvex tablets, covered with a film membrane of white or almost white color, with engraving "AZ" and "250" on one side and smooth on the other.

    Tablets 500 mg: Oval, biconvex tablets, covered with a film membrane of white or almost white color, with a risk and engraving "AZ" and "500" on one side and smooth on the other.

    Pharmacotherapeutic group:Antibiotic - azalide
    ATX: & nbsp

    J.01.F.A.10   Azithromycin

    Pharmacodynamics:

    Azithromycin is a bacteriostatic broad-spectrum antibiotic from the group of macrolides-azalides. It has a wide spectrum of antimicrobial action. The mechanism of action of azithromycin is associated with the suppression of protein synthesis of a microbial cell. Linking to the 508 subunit of the ribosome, inhibits peptidranslokase at the stage of translation, inhibits protein synthesis, slows the growth and multiplication of bacteria. In high concentrations has a bactericidal effect.

    It has activity against a number of gram-positive, gram-negative, anaerobic, intracellular and other microorganisms. Microorganisms can be initially resistant to the action of the antibiotic or can acquire resistance to it.

    The sensitivity scale of microorganisms to azithromycin (minimal inhibitory concentration (MIC), mg / l):

    Microorganisms

    MIC (mg / L)


    Sensitive

    Sustainable


    Streptococcus spp.

    1

    >2


    Streptococcus A, B, C, G

    0,25

    >0,5


    S. pneumoniae

    0,25

    >0,5

    H. influenzae

    0,12

    >4

    M. catarrhalis

    0,5

    >0,5

    N. gonorrhoeae

    0,25

    >0,5

    Sensitive:

    aerobic Gram-positive microorganisms:

    Staphylococcus aureus (methicillin-sensitive); Streptococcus pneumoniae (penicillin-sensitive); Streptococcus pyogenes; Aerobic Gram-negative microorganisms:

    Haemophilus influenzae; Haemophilus parainfluenzae; Legionella pneumophila; Moraxella catarrhalis; Pasteurella multocida; Neisseria gonorrhoeae; anaerobic microorganisms:

    Clostridium perfringens; Fusobacterium spp .; Prevotella spp .; Porphyriomonas spp .;

    other:

    Chlamydia trachomatis; Chlamydia pneumoniae; Chlamydia psittaci; Mycoplasma pneumoniae; Mycoplasma hominis; Borrelia burgdorferi;

    Microorganisms that can develop resistance to azithromycin: aerobic Gram-positive microorganisms: Streptococcus pneumoniae (penicillin-resistant).

    Stable microorganisms:

    aerobic Gram-positive microorganisms: Enterococcus faecalis; Staphylococcus spp. (methicillin-resistant staphylococci with very high frequency have acquired resistance to macrolides). Azithromycin It is not active against strains of gram-positive bacteria resistant to erythromycin.

    Anaerobes: Bacteroides fragilis.

    Pharmacokinetics:

    After oral administration azithromycin well absorbed and quickly distributed in the body. After oral administration of 500 mg, the maximum concentration of azithromycin in the blood plasma is achieved after 2-3 hours and is 0.4 mg / l. Bioavailability is 37% (the effect of "first passage" through the liver). The apparent volume of distribution is 31.1 l / kg, the binding with proteins is inversely proportional to the concentration in the blood and is 7-50%. Penetrates through cell membranes. It is transported by phagocytes to the site of infection, where it is released in the presence of bacteria.Easily penetrates through the histohematological barriers and enters the tissues. Concentration in tissues and cells is 10-50 times higher than in plasma, and in the focus of infection - 24-34% more than in healthy tissues.

    In the liver demethylated, the metabolites formed are not active. In azithromycin, a very long half-life is 35-50 hours. The half-life of the tissues is much longer. The therapeutic concentration of azithromycin is maintained up to 5-7 days after the last dose. Azithromycin is excreted mainly in unchanged form - 50% of the intestine, 6% of the kidneys.

    Indications:

    Infectious-inflammatory diseases caused by microorganisms susceptible to azithromycin:

    1) infections of the upper respiratory tract and ENT organs: sinusitis, tonsillitis, pharyngitis, otitis media;

    2) infections of the lower respiratory tract: acute bronchitis, exacerbation of chronic bronchitis, pneumonia, including caused by atypical pathogens;

    3) infections of the skin and soft tissues: acne vulgaris of medium severity, erysipelas, impetigo, secondarily infected dermatoses;

    4) the initial stage of Lyme disease (borreliosis) - migrating erythema (erythema migrans);

    5) urinary tract infections caused by Chlamidia trachomatis (urethritis, cervicitis).

    Contraindications:

    1) hypersensitivity to azithromycin, other macrolides or ketolides, or other components of the drug;

    2) severe hepatic insufficiency (Child-Pugh class C);

    3) severe renal dysfunction (creatinine clearance (CK) less than 40 ml / min);

    4) children under 12 years old with a body weight of up to 45 kg;

    5) the period of breastfeeding;

    6) simultaneous reception with ergotamine and dihydroergotamine.

    Carefully:

    1) pregnancy;

    2) myasthenia gravis;

    3) mild to moderate liver dysfunction;

    4) mild and moderate renal dysfunction (CC more than 40 ml / min);

    5) arrhythmia, in the presence of proarrhythmogenic factors (especially in elderly patients), including congenital or acquired lengthening of the interval QT: in patients receiving antiarrhythmic drugs in classes IA (quinidine, procainamide), III (dofetil, amiodarone, sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin, levofloxacin), in patients with disturbances of vodnoelektrolitnogo balance, especially in the case of hypokalemia or hypomagnesemia, clinically significant bradycardia, cardiac arrhythmia or severe heart failure;

    6) simultaneous use of terfenadine, warfarin, digoxin, cyclosporine.

    Pregnancy and lactation:

    Azithromycin penetrates the placenta. Use during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.

    If azithromycin is to be used during lactation, the question of stopping breastfeeding should be resolved.

    Dosing and Administration:

    Inside, without chewing, 1 hour before or 2 hours after eating, once a day. Adults and children over 12 years of age with a body weight of over 45 kg:

    When infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues: 0.5 g / day for 1 reception for 3 days (exchange dose - 1.5 g).

    With acne ordinary medium severity: 0.5 g / day for 1 reception for 3 days, then 0.5 g / day for 1 reception once a week for 9 weeks. The course dose is 6.0 g. The first weekly tablet should be taken 7 days after taking the first daily tablet (the 8th day from the start of treatment), the subsequent 8 weekly tablets - with an interval of 7 days.

    In cases of urinary tract infections caused by Chlamydia trachomatis (uncomplicated urethritis or cervicitis): once 1 g.

    With Lyme disease (the initial stage of borreliosis is migrating erythema (erythema migrans)): 1 g for 1 reception on the first day and 0.5 g for 1 reception daily from 2 to 5 days. The course dose is 3 g.

    Assignment to patients with impaired function kidneys: for patients with mild and moderate impairment of renal function (creatinine clearance> 40 ml / min) dose adjustment is not required.

    Purpose for patients with impaired hepatic function: for patients with mild and moderate dysfunction of the liver, dose adjustment is not required.

    Elderly patients: correction of the dose is not required. Because elderly patients may already have proarrhythmogenic conditions, caution should be exercised when using the drug because of the high risk of arrhythmia, including pirouette.

    Side effects:

    Classification of adverse reactions according to the frequency of development:

    very often - not less than 10%,

    often - not less than 1%, but less than 10%,

    infrequently - not less than 0.1%, but less than 1%,

    rarely - not less than 0.01%, but less than 0.1%,

    very rarely - less than 0.01%,

    The unknown frequency can not be estimated from the available data.

    Infectious diseases: infrequently, candidiasis, including the oral and genital mucosa, pneumonia, pharyngitis, gastroenteritis, respiratory diseases, rhinitis. An unknown frequency is pseudomembranous colitis.

    From the side of metabolism and nutrition: often - anorexia.

    Allergic reactions: often - itchy skin, skin rash; infrequently - hypersensitivity reaction, photosensitization reaction, urticaria, Stevens-Johnson syndrome, angioedema, dermatitis, dry skin, sweating; very rarely - anaphylactic reaction, erythema multiforme, toxic epidermal necrolysis.

    From the blood and lymphatic systems: often - eosinophilia, lymphopenia, basophilia, monocytosis, an increase in the number of neutrophils; infrequently - leukopenia, neutropenia; very rarely - thrombocytopenia, hemolytic anemia.

    From the central nervous system: often - headache, dizziness, paresthesia, a violation of taste sensations; infrequently - nervousness, hypoesthesia, drowsiness, insomnia; rarely - agitation; very rarely - anxiety, aggression, fainting, convulsions, psychomotor hyperactivity, disorders, perversion and loss of sense of smell, loss of taste, myasthenia gravis, delirium, hallucinations.

    From the side of the organ of vision: often - a violation of the clarity of visual perception.

    From the side of the hearing organ and labyrinthine disorders: infrequently - hearing disorder, vertigo; unknown frequency - hearing impairment, including deafness, tinnitus.

    From the cardiovascular system: infrequently - a feeling of palpitations, "tides" of blood to the face; unknown frequency - lowering blood pressure, increasing the interval QT, arrhythmia such as "pirouette", ventricular tachycardia.

    From the respiratory system: infrequently - shortness of breath, nosebleed.

    From the gastrointestinal tract: very often - nausea, flatulence, abdominal pain, diarrhea; often - indigestion, vomiting; infrequent - constipation, gastritis, dysphagia, bloating, dryness of the oral mucosa, belching, ulcers of the oral mucosa, increased secretion of the salivary glands; very rarely - a discoloration of the tongue, pancreatitis.

    From the liver and bile ducts: infrequently - hepatitis; rarely - a violation of liver function; very rarely - cholestatic jaundice, hepatic insufficiency (in rare cases with a fatal outcome mainly on the background of severe impairment of liver function), liver necrosis, fulminant hepatitis.

    From the osteomuscular system and connective tissue: infrequently - osteoarthritis, myalgia, back pain, neck pain; unknown frequency - arthralgia.

    From the side of the kidneys and urinary tract: infrequently - dysuria, pain in the kidney; unknown frequency - interstitial nephritis, acute renal failure.

    From the genitals and mammary glands: infrequently - metrorrhagia, dysfunctions of testicles.

    Laboratory indicators: often - a decrease in the concentration of bicarbonates in the blood plasma; Infrequent - increased activity "liver" enzymes, increasing the concentration of bilirubin in blood plasma, increasing the concentration of urea and creatinine in blood plasma, a change in the potassium concentration in the blood plasma, increased alkaline phosphatase activity, increasing the concentration of chlorine and plasma glucose, the increase in the platelet count, increased hematocrit, increased concentrations of bicarbonates and changes in the concentration of sodium in the blood plasma.

    Other: infrequently - asthenia, malaise, fatigue, face swelling, chest pain, peripheral edema, fever.

    Overdose:

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

    Treatment: gastric lavage, symptomatic therapy.

    Interaction:

    Antacids do not affect the bioavailability of azithromycin, but reduce the maximum concentration in the blood by 30%, so the drug should be taken at least one hour before or two hours after taking these drugs and food.

    Simultaneous use of azithromycin with cetirizine (20 mg) for 5 days in healthy volunteers did not lead to a pharmacokinetic interaction and a significant change in the interval QT.

    The simultaneous use of azithromycin (1200 mg / day) and didanosine (400 mg / day) in 6 HIV-infected patients showed no change in the pharmacokinetic indices of didanosine compared with the placebo group. Simultaneous use of macrolide antibacterial drugs, including azithromycin, with P-glycoprotein substrates, such as digoxin, leads to an increase in the concentration of the P-glycoprotein substrate in the blood plasma. Thus, with the simultaneous use of digoxin and azithromycin, it is necessary to consider the possibility of increasing the concentration of digoxin in the blood plasma.

    The simultaneous use of azithromycin (a single dose of 1000 mg and repeated administration of 1200 mg or 600 mg) has little effect on the pharmacokinetics, including the excretion of zidovudine or its glucuronide metabolite by the kidneys. Nevertheless, the concentration of the active metabolite - phosphorylated zidovudine - increases in peripheral blood mononuclear cells.The clinical significance of this fact is unclear. Azithromycin weakly interacts with isoenzymes of the cytochrome P450 system. It was not revealed that azithromycin participates in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin is not an inhibitor and inducer of cytochrome P450 isoenzymes.

    Given the theoretical possibility of developing ergotism, the simultaneous use of azithromycin with derivatives of ergot alkaloids is not recommended.

    Pharmacokinetic studies of the simultaneous use of azithromycin and drugs whose metabolism occurs with the participation of cytochrome P450 isoenzymes have been carried out.

    Atorvastatin: simultaneous use of atorvastatin (100 mg daily) and azithromycin (500 mg daily) did not cause changes in the concentration of atorvastatin in the blood plasma (based on the inhibition of GMA-CoA reductase). However, in the post-marketing period, reports were received of cases of rhabdomyolysis in patients receiving concomitantly azithromycin and statins.

    Carbamazepine: in pharmacokinetic studies involving healthy volunteers, no significant effect onthe concentration of carbamazepine and its active metabolite in blood plasma with simultaneous use with azithromycin.

    Cimetidine: In pharmacokinetic studies of the effect of a single dose of cimetidine on the pharmacokinetics of azithromycin, no changes in the pharmacokinetics of azithromycin have been observed, provided cimetidine is administered 2 hours before azithromycin.

    Anticoagulants of indirect action (coumarin derivatives): in pharmacokinetic studies azithromycin did not affect the anticoagulant effect of warfarin in a single dose of 15 mg, taken by healthy volunteers. Potential anticoagulant effect was reported after simultaneous use of azithromycin and indirect anticoagulants (coumarin derivatives). Despite the fact that a causal relationship has not been established, it is recommended to carefully monitor prothrombin time in patients, while using azithromycin and indirect anticoagulants (coumarin derivatives). Cyclosporine: in pharmacokinetic studies involving healthy volunteers who within 3 days were ingested azithromycin (500 mg / day once), and then ciclosporin (10 mg / kg / day once), a significant increase in the maximum concentration in plasma and the area under the "concentration-time" curve of cyclosporine. Care should be taken when using these drugs at the same time. In case of simultaneous use of these drugs, it is necessary to monitor the concentration of cyclosporine in the blood plasma and adjust the dose accordingly.

    Efavirenz: simultaneous use of azithromycin (600 mg / day once) and efavirenz (400 mg / day) daily for 7 days did not cause any clinically significant pharmacokinetic interaction. Fluconazole: simultaneous use of azithromycin (1200 mg once) did not change the pharmacokinetics of fluconazole (800 mg once). The total exposure and half-life did not change with the simultaneous use of fluconazole, however, a decrease in the maximum concentration of azithromycin by 18% was noted, which was not clinically significant.

    Indinavir: simultaneous use of azithromycin (1200 mg once) did not cause a statistically significant effect on the pharmacokinetics of indinavir (800 mg three times daily for 5days).

    Methylprednisolone: azithromycin has no significant effect on the pharmacokinetics of methylprednisolone.

    Nelfinavir: simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg three times a day) causes an increase in the equilibrium concentrations of azithromycin in the blood plasma. Clinically significant side effects were not observed and correction of the dose of azithromycin with its simultaneous application with nelfinavir is not required.

    Rifabutin: simultaneous use of azithromycin and rifabutin does not affect the concentration of each drug in the blood plasma. With the simultaneous use of azithromycin and rifabutin, neutropenia was sometimes observed. Despite the fact that neutropenia was associated with the use of rifabutin, a causal relationship between the use of a combination of azithromycin and rifabutin and neutropenia has not been established.

    Sildenafil: when used in healthy volunteers, no evidence of the effect of azithromycin (500 mg / day daily for 3 days) was found to have no significant effect on the maximum plasma concentration and area under the concentration-time curve of sildenafil and its main metabolite.

    Terfenadine: in pharmacokinetic studies, there was no evidence of interaction between azithromycin and terfenadine. It was reported about isolated cases where the possibility of such interaction could not be excluded completely, but there was no specific evidence that such an interaction took place. It was found that the simultaneous use of terfenadine and antibiotics of the macrolide class causes arrhythmia and lengthening of the interval QT.

    Theophylline: no interaction between azithromycin and theophylline.

    Triazolam / midazolam: no significant changes in pharmacokinetic parameters were observed with simultaneous use of azithromycin with triazolam or midazolam in therapeutic doses.

    Trimethoprim / sulfamethoxazole: simultaneous use of trimethoprim / sulfamethoxazole with azithromycin has not shown a significant effect on the maximum concentration, total exposure or excretion of trimethoprim or sulfamethoxazole by the kidneys. The concentration of azithromycin in the blood plasma was consistent with that found in other studies.

    Special instructions:

    If you miss one dose of Azithromycin-LEXVM®, the missed dose should be taken as soon as possible, and the subsequent dose should be taken with interruptions of 24 hours.

    Azithromycin should be taken at least 1 hour before or 2 hours after taking antacid medicines.

    The drug should be used with caution in patients with mild and moderate impairment of liver function due to the possibility of developing fulminant hepatitis and severe hepatic insufficiency.

    In the presence of symptoms of liver dysfunction, such as rapidly increasing asthenia, jaundice, darkening of the urine, a tendency to bleeding, hepatic encephalopathy, drug therapy should be discontinued and a study of the functional state of the liver should be carried out.

    For mild to moderate renal dysfunction (CC greater than 40 mL / min), Azithromycin-LEXVM® should be administered with caution under the control of the kidney function.

    As with the use of other antibacterial drugs, patients with azithromycin therapy should be examined regularly for the presence of non-susceptible microorganisms and signs of development of superinfections, including fungal ones.

    The drug Azithromycin-LEXVM® should not be used with longer courses than indicated in the instructions, since the pharmacokinetic properties of azithromycin allow us to recommend a short and simple dosing regimen.

    There is no data on the possible interaction between azithromycin and derivatives of ergotamine and dihydroergotamine, but due to the development of ergotism with the simultaneous use of macrolides with derivatives of ergotamine and dihydroergotamine, this combination is contraindicated.

    With prolonged use of the drug, the development of pseudomembranous colitis caused by Clostridium difficile, as in the form of mild diarrhea, and severe colitis. With the development of diarrhea against the background of taking azithromycin, and also 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded.

    Syndrome of delayed repolarization of the ventricles - syndrome of lengthening the interval QT -increases the risk of arrhythmias, including arrhythmias such as "pirouette" against the background of taking macrolides, as well as the drug Azithromycin-LEXVM®. Caution when using azithromycin should be observed in patients with proarrhythmogenic factors (especially in elderly patients),including with congenital or acquired lengthening of the interval QT: in patients receiving antiarrhythmic drugs in classes IA (quinidine, procainamide), III (dofetil, amiodarone, sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin, levofloxacin), in patients with disturbed water-electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, clinically significant bradycardia, cardiac arrhythmia or severe heart failure.

    The use of azithromycin may provoke the development of a myasthenic syndrome or cause an exacerbation of myasthenia gravis.

    Effect on the ability to drive transp. cf. and fur:

    Given the likelihood of side effects from the nervous system and the organ of vision, caution should be exercised when driving vehicles and during occupations with potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

    Form release / dosage:

    The tablets covered with a film membrane 250 mg, 500 mg.

    Packaging:

    Tablets 250 mg

    3 tablets per blister from Al / PVC.1 or 2 blisters are placed in a cardboard box together with an instruction for use.

    Tablets 500 mg

    3 tablets per blister from Al / PVC. 1 or 2 blisters are placed in a cardboard box together with an instruction for use.

    Storage conditions:

    In a dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after expiry date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002817
    Date of registration:13.01.2015 / 25.06.2015
    Expiration Date:13.01.2020
    The owner of the registration certificate:PROTEK-SVM, LLC PROTEK-SVM, LLC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp22.06.2017
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