Active substanceAzithromycinAzithromycin
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  • Dosage form: & nbsplyophilizate for solution for infusion
    Composition:

    1 bottle contains:

    Active ingredient: Azithromycin dihydrate 524.10 mg azithromycin, based on 500.00 mg;

    Excipients: Citric acid monohydrate 420.56 mg 188.00 mg sodium hydroxide, sodium hydroxide q.s.

    Description:The lyophilized powder is white or almost white in color.
    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. By binding to 505-subunit of the ribosome inhibits peptidtranslokazu to the broadcast stage and inhibits protein synthesis by slowing growth and reproduction 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 (Minimal 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

    H. influenzae

    <0,12

    > 4

    M. catarrhal is

    <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:

    Azithromycin rapidly penetrates from the blood serum into the tissues. Concentrating in phagocytes and not breaking their functions, azithromycin migrates to the focus of inflammation, accumulating directly in infected tissues.

    The pharmacokinetics of azithromycin in healthy volunteers after a single intravenous infusion lasting more than 2 hours in a dose of 1000-4000 mg (concentration of the solution 1 mg / ml) is linear and proportional to the administered dose. The half-life of the drug is 65-72 hours. A high level of the observed volume of distribution (33.3 l / kg) and plasma clearance (10.2 ml / min / kg) suggests that a long half-life of the drug is a consequence of the accumulation of antibiotic in tissues followed by its slow release.

    In healthy volunteers with intravenous infusion of azithromycin 500 mg (concentration of the solution I mg / ml) for 3 hours, the maximum concentration of the drug in the blood serum was 1.14 μg / ml. The minimum serum level (0.18 μg / ml) was observed for 24 hours and the area under the concentration-time curve was 8.03 μg-h / ml. Similar pharmacokinetic values ​​were also obtained in patients with community-acquired pneumonia who received intravenous infusions (3 hrs) for 2 to 5 days.

    Following administration of azithromycin daily dose of 500 mg (infusion duration 1 hour) for 5 days on average 14% of the dose is excreted by the kidneys during the 24 hour dosing interval.

    The drug is metabolized in the liver. Metabolites do not have antimicrobial activity.

    Indications:

    - Community-acquired pneumonia of severe course caused by Chlamydia pneumoniae, Haemophilus influenzae, Legionella pneumophila, Moraxella catarrhalis, Mycoplasma pneumoniae, Staphylococcus aureus or Streptococcus pneumoniae

    - Infectious-inflammatory diseases of small pelvic organs of severe course (endometritis and salpingitis), caused by Chlamydia trachomatis, or Neisseria gonorrhoeae and Mycoplasma hominis

    Contraindications:

    Hypersensitivity to azithromycin, erythromycin, other macrolides or ketolides, or other components of the drug; heavy abnormal liver function; severe renal dysfunction (creatinine clearance (CK) less than 40 ml / min); children's age till 18 years; simultaneous reception with ergotamine and dihydroergotamine.

    Carefully:

    Myasthenia gravis; mild to moderate liver dysfunction; 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 of 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 heart failure; 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.
    Dosing and Administration:

    Intravenously (iv) drip for 3 hours infusion solution at a concentration of 1 mg / ml, for 1 hour - at a concentration of 2 mg / ml. It is necessary to avoid the introduction of higher concentrations due to hazard the occurrence of reactions at the injection site.

    Sumamed® can not be injected intravenously in a jet or intramuscular injection.

    Community-acquired pneumonia

    500 mg / day iv once a day for at least two days (if necessary, the treatment course may be prolonged, but not more than 5 days, as decided by the doctor in charge). After the end of intravenous administration, the use of azithromycin for oral administration at a dose of 500 mg / day is recommended once to complete the 7-10 day general course of treatment.

    Infectious-inflammatory diseases of the pelvic organs

    500 mg / day IV once a day for 2 days (iv treatment is no more than 5 days). After the end of intravenous administration, the use of azithromycin for oral administration at a daily dose of 250 mg / day is recommended once until the complete completion of the 7-day general course of treatment.

    The period of the transition from intravenous administration to the reception of Sumamed ® is determined by the physician in accordance with the data of the clinical examination.

    In case of impaired renal function: at use in patients with mild to moderate renal dysfunction (KC more than 40 ml / min) dose adjustment is not required.

    When a violation of liver function: when application in patients with mild and moderate dysfunction of the liver dose adjustment is not required.

    Elderly patients: correction of the dose is not required.Since the elderly are already may have ongoing pro-arrhythmogenic conditions, caution should be exercised when using Sumamed®, due to the high risk of developing cardiac arrhythmias, including pirouette-type arrhythmias.

    Children under 18 years of age: efficacy and safety of use in children of the dosage form of the drug Sumamed ", intended for intravenous infusions, has not been established.

    Solution for infusion is prepared in 2 stages:

    Stage 1 - Preparation of the reconstituted solution. To the contents of the vial (500 mg of azithromycin) 4.8 ml of sterile water for injection are added and shaken thoroughly until the powder is completely dissolved. In 1 ml of reconstituted solution contains 100 mg of azithromycin.

    The reconstituted solution should be used immediately for further dilution.

    The reconstituted solution is checked for the absence of visible undissolved particles, otherwise the solution should not be used.

    2 stage - dilution of reconstituted solution (100 mg / ml) is administered immediately before administration according to the table below.

    The concentration of azithromycin

    amount

    solvent

    in solution


    for infusions


    1.0 mg / ml

    500 ml

    2.0 mg / ml

    250 ml

    In the vial with the solvent (physiological solution - 0.9% sodium chloride, 5% dextrose solution, Ringer's solution), add the reconstituted solution to a final concentration of azithromycin of 1.0-2.0 mg / ml. The prepared solution is checked for the absence of visible undissolved particles, otherwise the solution should not be used.

    The prepared diluted solution should be used immediately.

    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 oral and genital mucosa, 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; unknown frequency - anaphylactic reaction.

    From the nervous system: often - headache; infrequently - dizziness, a violation of taste, 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 side of the cardiovascular system: infrequently - a feeling of palpitations, "tides" of blood to the face; unknown frequency - lowering blood pressure, increasing the interval QT on the electrocardiogram, arrhythmia of the type "pirouette", 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 - a violation of the liver, 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, violation functions of the testicles.

    Local reactions: often pain and inflammation at the injection site.

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

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

    Overdose:

    Symptoms: nausea, temporary hearing loss, vomiting, diarrhea, abdominal pain, abnormal liver function.

    Treatment: symptomatic.

    Interaction:

    Cetirizine

    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.

    Didanosine (dideoxyinosine)

    Simultaneous use of azithromycin (1200 mg / day) and didanosine (400 mg / day) in 6 HIV-infected patients showed no change in the pharmacokinetic indications of 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 the simultaneous use of azithromycin and digoxin, it is necessary to take into account the possibility of increasing the concentration of digoxin in the blood serum.

    Zidovudine

    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.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 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 It is not an inhibitor and inducer of cytochrome P450 isoenzymes.

    Alkaloids of ergot

    Given the theoretical possibility of the emergence of 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

    The simultaneous use of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause a change in the concentrations of atorvastatin in blood plasma (based on the inhibition of HMG-CoA reductase). However, in the post-marketing period, separate reports were received on cases of rhabdomyolysis in patients receiving concomitantly azithromycin and statins.

    Carbamazepine

    In pharmacokinetic studies involving healthy volunteers, no significant effect on the concentration of carbamazepine and its active metabolite in blood plasma in patients receiving concomitantly azithromycin.

    Cimetidine

    In pharmacokinetic studies the effect of a single dose of cimetidine on the pharmacokinetics of azithromycin showed no changes in the pharmacokinetics of azithromycin, 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 dose of 15 mg of warfarin taken by healthy volunteers. Potentialization has been reported anticoagulant effect after simultaneous use of azithromycin and anticoagulants of indirect action (coumarin derivatives). Although there is no causal relationship, consideration should be given to the need for frequent monitoring prothrombin time with the use of azithromycin in patients who receive oral anticoagulants indirect action (derivatives coumarin).

    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 "concentration-time" curve (AUC0-5) cyclosporine. Care should be taken when using these drugs at the same time. If necessary, simultaneous use of these drugs, it is necessary to monitor the concentration of cyclosporine in the blood plasma and, accordingly, adjust the dose.

    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 of azithromycin did not change with simultaneous application of fluconazole, however, a decrease in Cmah azithromycin (by 18%), which had no clinical significance.

    Indinavir

    Simultaneous use of 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 significantly affect the pharmacokinetics methylprednisolone.

    Nelfinavir

    Simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times a day) causes an increase in the equilibrium concentrations of azithromycin in the blood serum. 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 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 has not been established.

    Sildenafil

    When used in healthy volunteers, 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. Individual cases were reported where the possibility of such interaction could not be ruled out completely, but there was not one concrete proof 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. Concentrations azithromycin in the serum corresponded to those detected in other studies.

    Special instructions:

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

    In the presence of symptoms of liver dysfunction, such as rapidly growing asthenia, jaundice, darkening of the urine, a tendency to bleeding, hepatic encephalopathy with Sumamed® should be stopped and a study of the functional state of the liver.

    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 pro-arrhythmic factors (especially in elderly patients), including congenital or acquired lengthening of the interval QT; in patients taking antiarrhythmic drugs classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with violations water-electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, clinically significant bradycardia, cardiac arrhythmia or severe heart failure.

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

    Efficacy and safety of use in children under 18 years of the medicinal form of the drug Sumamed ®, intended for IV infusion, is not established. Patients on a diet with limited sodium intake should be aware of the fact that one bottle contains 198.3 mg of sodium (sodium hydroxide is an auxiliary substance) when treated with Sumamed®.

    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:

    Liofilizate for the preparation of a solution for infusions 500mg.

    Packaging:

    By 500 mg of the active ingredient in a glass colorless vial,Corked with bromobutyl or chlorobutyl cork and crimped with an aluminum cap.

    5 vials with instructions for use in a cardboard box.

    Storage conditions:

    List B.

    Lyophilizate - at a temperature not exceeding 25 ° С.

    The prepared solution - use immediately.

    Shelf life:

    2 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:П N015662 / 01
    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: & nbsp20.08.2015
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