Active substanceAzithromycinAzithromycin
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  • Dosage form: & nbspcapsules
    Composition:

    1 capsule contains:

    active substance azithromycin dihydrate 262.05 mg, in terms of azithromycin - 250 mg;

    auxiliary substances: microcrystalline cellulose 43.95 mg, sodium lauryl sulfate 1.40 mg, magnesium stearate 12.60 mg.

    Hard gelatin capsule No. 1 ** 75.00 mg, gelatin q.s., titanium dioxide (E-171) q.s., indigocarmine q.s.

    ** - capsules contain sulfur dioxide 200 ppmm as a preservative.

    Description:

    Hard gelatin capsules №1, the case of blue color, the lid of blue color. The contents of the capsules are a powder or compacted mass from white to light yellow, disintegrating when pressed.

    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. Communicating with 50S-a subunit of the ribosome, inhibits peptidranslokase at the stage of translation and inhibits protein synthesis, slowing the growth and multiplication of bacteria. In high concentrations has a bactericidal effect.

    It has activity against a number of gram-positive, gram-negative, anaerobes, intracellular and other microorganisms.

    Microorganisms may initially be resistant to the action of the antibiotic or may acquire resistance to it.

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

    Microorganisms

    MIC, mg / l

    Sensitive

    Sustainable

    Staphylococcus

    < 1

    >2

    Streptococcus A, B, C, G

    <0,25

    >0,5

    S. pneumonia

    <0,25

    >0,5

    AND. influenzae

    <0,12

    > 4

    M. catarrhalis

    <0,5

    >0,5

    N. gonorrhoeae

    <0,25

    >0,5

    In most cases, sensitive microorganisms

    - Gram-positive aerobes

    Staphylococcus aureus Methicillin-sensitive
    Streptococcus
    pneumoniae Penicillin-sensitive
    Streptococcus
    pyogenes

    - Gram-negative aerobes

    Haemophilus influenzae
    Haemophilus parainfluenzae

    Legionella pneumophila

    Moraxella catarrhalis

    Pasteurella multocida

    Neisseria gonorrhoeae

    - Anaerobes

    Clostridium perfringens
    Fusobacterium spp.

    Prevotella spp.

    Porphyriomonas spp.

    - Other microorganisms

    Chlamydia trachomatis
    Chlamydia pneumoniae

    Chlamydia psittaci

    Mycoplasma pneumoniae

    Mycoplasma hominis

    Borrelia burgdorferi

    Microorganisms capable of developing resistance to azithromycin

    Gram-positive aerobes

    Streptococcus pneumoniae Penicillin-stable

    Initially, resistant microorganisms

    Gram-positive aerobes

    Enterococcus faecalis

    Staphylococci (methicillin-resistant staphylococci exhibit a very high degree of resistance to macrolides)

    Gram-positive bacteria resistant to erythromycin.

    Anaerobes

    Bacteroides fragilis

    Pharmacokinetics:

    After oral administration azithromycin well absorbed and quickly distributed in the body. After a single dose of 500 mg bioavailability is 37% (the effect of "first pass"), the maximum concentration (0.4 mg / l) in the blood is created after 2-3 hours, the apparent volume of distribution is 31.1 l / kg, protein binding inversely proportional to the concentration in the blood and is 7-50%. Penetrates through cell membranes (effective for infections caused by intracellular pathogens). It is transported by phagocytes to the site of infection, where it is released in the presence of bacteria. Easily passes 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 azithromycin, a very long half-life is 35-50 hours. The half-life of tissues is much longer. The therapeutic concentration of azithromycin is maintained to 5-7 days after the last dose. Azithromycin is output, basically, in the unchanged form - 50% of the intestine, 6% of the kidneys. In the liver, demethylated, losing activity.

    Indications:

    Infectious-inflammatory diseases caused by microorganisms sensitive to the preparation:

    - Infections of the upper respiratory tract and ENT organs (pharyngitis / tonsillitis, sinusitis, otitis media);

    - Infections of the lower respiratory tract: acute bronchitis, exacerbation of chronic bronchitis, pneumonia, incl. caused by atypical pathogens;

    - Infections of the skin and soft tissues (erysipelas, impetigo, secondarily infected dermatoses);

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

    - Urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis).
    Contraindications:

    Increased sensitivity to azithromycin, erythromycin, other macrolides or ketolides, or other components of the preparation; Heavy hepatic insufficiency (Child-Pugh class C); severe renal dysfunction (creatinine clearance (CK) less than 40 ml / min); children under 12 years of age with a body weight of less than 45 kg; simultaneous reception with ergotamine and dihydroergotamine.

    Carefully:

    Myasthenia gravis; light and moderate abnormal liver function; mild and moderate renal dysfunction (CC more than 40 ml / min); In patients with proarrhythmogenic factors (especially in elderly patients): with congenital or acquired lengthening the interval QT, in patients receiving therapy antiarrhythmic drugs classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with disturbances of water-electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, cardiac arrhythmia, or severe cardiac insufficiency; simultaneous use of digoxin, warfarin, cyclosporine.

    Pregnancy and lactation:In pregnancy and during breastfeeding apply only if the intended benefit to the mother exceeds the potential risk to the fetus and the baby. If it is necessary to use the drug during breastfeeding, it is recommended to suspend breastfeeding. WHO recommends azithromycin as a drug of choice in the treatment of chlamydial infection in pregnant women.
    Dosing and Administration:

    Inside, 1 time per day, at least 1 hour before or 2 hours after meals. Adults (including the elderly) and children over 12 years of age with a body weight of over 45 kg

    With infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues

    500 mg (2 capsules) 1 time per day for 3 days (course dose 1.5 g).

    With Lyme disease (the initial stage of borreliosis) - migratory erythema (erythema migrans)

    1 time per day for 5 days: 1st day - 1.0 g (4 capsules), then from 2 to 5 days - 500 mg (2 capsules) (course dose 3.0 g).

    With infections of the urogenital tract, caused by Chlamydia trachomatis (urethritis, cervicitis)

    Uncomplicated urethritis / cervicitis - 1 g (4 capsules) once.

    In case of impaired renal function: when used in patients with mild and moderate renal dysfunction (KC more than 40 ml / min) dose adjustment is not it takes.

    When a violation of liver function: when used in patients with mild and moderate impairment of liver function, dose adjustment is not required.

    Elderly patients: correction of the dose is not required. Since older people may already have current pro-rhythmogenic conditions, caution with the use of Sumamed ®, due to the high risk of developing cardiac arrhythmias, including arrhythmias such as pirouettes.

    Side effects:

    Frequency of side effects classified according to the recommendations of the World Health Organization: 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 mucous membrane of the oral cavity and genitals, pneumonia, pharyngitis, gastroenteritis, respiratory diseases, rhinitis; an unknown frequency is pseudomembranous colitis.

    On the part of the blood and lymphatic system: infrequently - leukopenia, neutropenia, eosinophilia; very rarely - thrombocytopenia, hemolytic anemia.

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

    Allergic reactions: infrequently angioedema, hypersensitivity reaction; an unknown frequency is an anaphylactic reaction.

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

    From the side of the organ of vision: infrequently - impaired vision.

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

    From the cardiovascular system: infrequently - a feeling of palpitations, "tides" of blood to the face; unknown frequency - lowering of arterial pressure, increase in QT interval on electrocardiogram, arrhythmia of "pirouette" type, ventricular tachycardia.

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

    From the gastrointestinal tract: very often - diarrhea; often - nausea, vomiting, abdominal pain; infrequent - meteorism, dyspepsia, 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 abnormal liver function, cholestatic jaundice; unknown frequency - hepatic insufficiency (in rare cases with a fatal outcome mainly on the background of severe violations of the liver function); liver necrosis, fulminant hepatitis.

    From the skin and subcutaneous tissues: infrequently - skin rash, itching, hives, dermatitis, dry skin, sweating; rarely - the reaction of photosensitization; unknown frequency - Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.

    From the musculoskeletal system: 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 the breast: infrequently - metrorrhagia, dysfunction of testicles.

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

    Laboratory data: often a decrease in the number of lymphocytes, an increase in the number of eosinophils, increasing the number of basophils, increasing number of monocytes, increase number of neutrophils, decrease concentration of bicarbonates in the blood plasma; infrequently, increased activity of aspartate aminotransferase, alanine aminotransferase, increased bilirubin concentration in the blood plasma, increased urea concentration in the blood plasma, increased plasma creatinine concentration, a change in potassium in the blood plasma, increased activity of alkaline phosphatase in the blood plasma, an increase in the level of chlorine in the blood plasma , an increase in the concentration of glucose in the blood, an increase in the number platelets, increase of hematocrit, increase of bicarbonate concentration in blood plasma, change of sodium content in blood plasma.

    Overdose:

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

    Treatment: symptomatic.

    Interaction:

    Antacid preparations

    Antacid preparations do not affect bioavailability 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.

    Cetirizine

    Simultaneous use within 5 days in healthy volunteers of azithromycin withcetirizine (20 mg) did not lead to pharmacokinetic interaction and significant change interval QT.

    Didanosine (dideoxyinosine)

    Simultaneous application azithromycin (1200 mg / day) and didanosine (400 mg / day) in 6 HIV-infected patients showed no changes in pharmacokinetic indications didanosine compared with the placebo group.

    Digoxin (substrates of P-glycoprotein)

    Simultaneous use of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates, such as digoxin, leads to an increase in the concentration of substrate P-glycoprotein in the blood serum. Thus, with simultaneous application of azithromycin and digoxin, the possibility of increasing the serum digoxin concentration blood.

    Zidovudine

    Simultaneous application azithromycin (a single dose of 1000 mg and multiple administration of 1200 mg or 600 mg) has little effect on the pharmacokinetics, including the excretion of zidovudine or its zidovudine glucuronide metabolite. However, the use of azithromycin caused an increase in the concentration phosphorylated zidovudine, a clinically active metabolite in peripheral blood mononuclear cells. The clinical significance of this fact dont clear.

    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 inductor isoenzymes of cytochrome P450.

    Alkaloids of ergot

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

    Pharmacokinetic studies were conducted simultaneous use of azithromycin and drugs whose metabolism occurs with participation of cytochrome P450 isoenzymes.

    Atorvastatin

    Simultaneous application Atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause a change in the concentrations of atorvastatin in the blood plasma (based on the inhibition of GMK-CoA reductase). However, in postregistrational period, separate reports were received on cases of rhabdomyolysis in patients receiving concomitantly azithromycin and statins.

    Carbamazepine

    In pharmacokinetic studies involving healthy volunteers, there was no significant effect on the concentration of carbamazepine and its active metabolite in blood plasma in patients receiving concomitantly 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 a single a dose of 15 mg of warfarin taken by healthy volunteers. Potential anticoagulant effect was reported after simultaneous use of azithromycin and indirect anticoagulants (coumarin derivatives). Although a causal relationship has not been established, consideration should be given to the need for frequent monitoring of prothrombin time when azithromycin is used in patients who receive oral anticoagulants of indirect action (coumarin derivatives).

    Cyclosporin

    In a pharmacokinetic study involving healthy volunteers who within 3 days were ingested azithromycin (500 mg / day once), and then ciclosporin (10 mg / kg / day once), there was a significant increase in the maximum concentration in the blood plasma (Cmax) and the area under the curve "concentration-time" (AUC0-5) 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 application azithromycin (600 mg / day once) and efavirenz (400 mg / day) daily for 7 days did not cause any clinically significant pharmacokinetic interaction.

    Fluconazole

    Simultaneous application azithromycin (1200 mg once) did not change the pharmacokinetics of fluconazole (800 mg once). The total exposure and the half-life of azithromycin did not change with the simultaneous use of fluconazole, but a decrease in Cmah azithromycin (by 18%), which had no clinical significance.

    Indinavir

    Simultaneous application azithromycin (1200 mg once) did not cause a statistically significant effect on the pharmacokinetics of indinavir (800 mg three times a day for 5 days).

    Methylprednisolone

    Azithromycin does not render significant impact on pharmacokinetics of methylprednisolone.

    Nelfinavir

    Simultaneous application azithromycin (1200 mg) and nelfinavir (750 mg 3 times a day) causes an increase in equilibrium concentrations azithromycin in serum. Clinically significant side effects were not observed and dose adjustment of azithromycin at its simultaneous application with nelfinavir is not required.

    Rifabutin

    Simultaneous application azithromycin and rifabutin does not affect the concentration of each of the drugs in the blood serum. 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 is not established.

    Sildenafil

    When used in healthy volunteers, no evidence of the effect of azithromycin (500 mg / day daily for 3 days) on AUC and Cmah sildenafil or its main circulating metabolite.

    Terfenadine

    In pharmacokinetic studies, no evidence was obtained interactions between azithromycin and terfenadine. It was reported about isolated cases, when the possibility of such interaction could not be excluded completely, but there was not a single one concrete evidence that such an interaction took place.

    It was found that the simultaneous use of terfenadine and macrolides may cause arrhythmia and lengthening of the interval QT.

    Theophylline

    There was no interaction between azithromycin and theophylline.

    Triazolam / midazolam

    Significant changes in pharmacokinetic parameters with the simultaneous use of azithromycin with triazolam or midazolam in therapeutic doses are not revealed.

    Trimethoprim / sulfamethoxazole

    Simultaneous use of trimethoprim / sulfamethoxazole with azithromycin did not reveal a significant effect on Cmah, total exposure or kidney excretion of trimethoprim or sulfamethoxazole. The concentrations of azithromycin in the serum corresponded to those detected in other studies.

    Special instructions:

    In case of missing one dose of Sumamed ® - the missed dose should be taken as soon as possible, and the subsequent dose - with interruptions of 24 hours.

    The drug Sumamed® should be taken at least one hour before or two hours after taking antacid preparations.

    Sumamed ® 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 impaired liver function, such as rapidly accruing asthenia, jaundice, darkening of the urine, a tendency to bleeding, hepatic encephalopathy therapy with Sumamed ® should be discontinued and a study of the functional state of the liver should be carried out.

    For mild to moderate renal dysfunction (KC more than 40 mL / min), Sumamed® should be administered with caution under the control of the kidney function.

    As with the use of other antibacterial drugs, with the treatment with Sumamed®, patients should be regularly monitored for the presence of non-susceptible microorganisms and signs of development of superinfections, including fungal ones.Sumamed ® 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 because of the development of ergotism with the simultaneous use of macrolides with derivatives of ergotamine and dihydroergotamine, this combination is not recommended.

    With long-term use of Sumamed®, it is possible to develop pseudomembranous colitis caused by Clostridium difficile, as in the form of mild diarrhea, and severe colitis. In the development of antibiotic-associated diarrhea against the background of taking the drug Sumamed®, and also 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded.

    When treating macrolides, including azithromycin, prolonged cardiac repolarization and interval QT, increasing the risk of developing cardiac arrhythmias, including arrhythmias such as pirouettes.

    Caution should be used when using Sumamed ® in patients with proarrhythmogenic factors (especially in elderly patients): with congenital or acquired interval lengthening QT, in patients receiving antiarrhythmic drug therapy classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with disturbances of the water-electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, cardiac arrhythmia, or severe cardiac insufficiency.

    The use of Sumamed ® can provoke the development of myasthenic syndrome or cause an exacerbation of myasthenia gravis.

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

    With the development of undesirable effects from the nervous system and the organ of vision, care should be taken when performing actions requiring increased concentration of attention and speed of psychomotor reactions.

    Form release / dosage:

    Capsules 250 mg.

    Packaging:

    6 capsules per blister of PVC / PVDC / aluminum foil.

    1 blister together with instructions for use in a cardboard box.

    Storage conditions:Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:П N015662 / 02
    Date of registration:18.05.2009
    The owner of the registration certificate:Pliva of Hrvatska dooPliva of Hrvatska doo Croatia
    Manufacturer: & nbsp
    Representation: & nbspPliva of Hvartska dooPliva of Hvartska doo
    Information update date: & nbsp26.10.2015
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