Composition, form of production and packaging
Tablets covered with a film membrane from white to almost white, round, biconvex.
azithromycin dihydrate 262.026 mg,
which corresponds to the content of azithromycin 250 mg
Excipients: corn pregelatinized corn starch - 42.5 mg, croscarmellose sodium - 9 mg, calcium hydrophosphate - 115.625 mg, magnesium stearate - 6.375 mg, sodium lauryl sulfate - 1.5 mg.
The composition of the membrane: hypromellose 2910/5 - 7.3 mg, titanium dioxide 3.1 mg, macrogol 6000-700 Ојg, talc 1.25 mg, emulsion simethicone SE4 (water 67.4%, siloxanes and silicones 30%, methylated cellulose 2.5% sorbic acid - 0.1%) - 50 Ојg, polysorbate 80 - 100 Ојg.
3 pcs. - blisters (1) - packs of cardboard.
3 pcs. - blisters (2) - packs of cardboard.
6 pcs. - blisters (1) - packs of cardboard.
Tablets, covered with a film shell from white to almost white, oblong.
azithromycin dihydrate 524.052 mg,
which corresponds to the content of azithromycin 500 mg
Excipients: corn pregelatinized corn starch - 85 mg, croscarmellose sodium - 18 mg, calcium hydrophosphate - 231.25 mg, magnesium stearate - 12.75 mg, sodium lauryl sulfate - 3 mg.
The composition of the membrane: hypromellose 2910/5 - 14.6 mg, titanium dioxide 6.2 mg, macrogol 6000 1.4 mg, talc 2.5 mg, emulsion simethicone SE4 (water 67.4%, siloxanes and silicones 30%, methylated cellulose 2.5% sorbic acid - 0.1%) - 100 Ојg, polysorbate 80 - 200 Ојg.
3 pcs. - blisters (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
Bacteriostatic antibiotic of a wide spectrum of action from the group of macrolides - azalides. 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 50S subunit of ribosomes, 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.
Gram-positive cocci are sensitive to azithromycin: Streptococcus pneumoniae (penicillin-sensitive strains), Streptococcus pyogenes, Staphylococcus aureus (methicillin-sensitive strains); aerobic gram-negative bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis, Pasteurella multocida, Neisseria gonorrhoeae; some anaerobic microorganisms: Clostridium perfringens, Fusobacterium spp., Prevotella spp., Porphyriomonas spp .; as well as Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.
Microorganisms with acquired resistance to azithromycin: aerobic gram-positive microorganisms-Streptococcus pneumoniae (penicillin-resistant strains and strains with moderate sensitivity to penicillin).
Microorganisms with natural resistance: aerobic gram-positive microorganisms - Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis (methicillin-resistant strains), anaerobic microorganisms - Bacteroides fragilis.
Cases of cross-resistance between Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococcus), Enterococcus faecalis and Staphylococcus aureus (methicillin-resistant strains) to erythromycin, azithromycin, other macrolides and lincosamides are described.
Azithromycin has not been used to treat infectious diseases caused by Salmonella typhi (MIC <16 mg / L) and Shigella spp.
The sensitivity scale of microorganisms to azithromycin (Minimum inhibitory concentration (MIC) mg / l).
Microorganisms MIC, mg / l
Staphylococcus spp. ? 1> 2
Streptococcus spp. (groups A, B, C, G)? 0.25> 0.5
Streptococcus pneumoniae? 0.25> 0.5
Haemophilus influenzae? 0.12> 4
Moraxella catarrhalis? 0.25> 0.5
Neisseria gonorrhoeae? 0.25> 0.5
Minimum inhibitory concentrations (MIC) of azithromycin.
MPC 90 (Ојg / ml) Microorganisms
MPC 90 В± 0.01 Ојg / ml Haemophilus ducreyi, Mycoplasma pneumoniae
IPC 90 0.01-0.1 Ојg / ml Actinomyces spp., Bordetella pertussis, Borrelia burgdorferi, Gardnerella vaginalis, Mobiluncus spp., Moraxella catarrhalis, Propionibacterium acnes
BMC 90 0.01-2 Ојg / ml Bacteriodes bivius, Bordetella parapertussis, Brucella melitensis, Campylobacter jejuni, Clostridium perfringens, Fusobacterium necrophorum, Haemophilus influenzae, Haemophilus parainfluenzae, Helicobacter pylori, Chlamydia pneumoniae, Chlamydia trachomatis, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella haemolytica, Pasteurella multocida , Peptococcus spp., Peptostreptococcus spp., Plesiomonas shigelloides, Staphylococcus aureus, Streptococcus agalactiae, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, Streptococcus group C, F, G, Ureaplasma urealyticum, Vibrio cholerae, Vibrio parahaemolyticus
IGK 90 2-8 Ојg / ml Acinetobacter calcoaceticus, Aeromonas hydrophylia, Bacteroides fragilis, Bacteroides oralis, Clostridium difficile, Escherichia coli, Eubacterium lentum, Fusobacterium nucleatum, Salmonella enteritidis, Salmonella typhi, Shigella sonnei, Yersinia enterocolitica
MIC> 90 > 10 Ојg / ml Citrobacter spp., Corynebacterium spp., Enterobacter aerogenes, Enterobacter cloacae, Enterococcus faecalis, Enterococcus faecium, Eubacterium limosum, Klebsiella pneumoniae, Klebsiella oxytoca, Mycoplasma hominis, Proteus spp., Pseudomonas aeruginosa, Serratia marcescens
After taking the drug inside, azithromycin is well absorbed from the digestive tract, which is due to its resistance in acidic environment and lipophilicity.
After a single intake of 500 mg of azithromycin C max in blood plasma is achieved after 2-3 hours and is 0.4 mg / l. Bioavailability is 37%.
Azithromycin is rapidly distributed in the body. It penetrates well into the respiratory tract, organs and tissues of the urogenital tract (in particular, into the prostate gland), into the skin and soft tissues. High concentrations in tissues (10-50 times higher than in plasma) and long T 1/2 are due to low binding of azithromycin to blood plasma proteins, as well as its ability to penetrate eukaryotic cells and concentrate in a medium with a low pH surrounding the lysosome . This, in turn, determines a large apparent V d (31.1 l / kg) and high plasma clearance. The ability of azithromycin to accumulate mainly in lysosomes is especially important for the eradication of intracellular pathogens. It is proved that phagocytes deliver azithromycin to the site of infection, where it is released during phagocytosis.
The concentration of azithromycin in the foci of infection is significantly higher than in healthy tissues (an average of 24-34%). Despite the high concentration in phagocytes, azithromycin does not significantly affect their function.
Binding to plasma proteins - 7-50% (inversely proportional to the concentration in the blood).
In the liver demethylated, the metabolites formed are not active.
In azithromycin, the long T 1/2 is 35-50 hours. The therapeutic concentration of azithromycin is maintained up to 5-7 days after the last dose, which allows the development of short (3-day and 5-day) courses of treatment. Azithromycin is excreted mainly unchanged: 50% through the intestine, 6% - by the kidneys.
Infectious-inflammatory diseases caused by microorganisms susceptible to azithromycin:
- infections of the upper respiratory tract and ENT organs (sore throat, sinusitis, tonsillitis, pharyngitis, otitis media);
- Infections of the lower respiratory tract (acute bronchitis, exacerbation of chronic bronchitis, pneumonia, including those caused by atypical pathogens);
- infections of the skin and soft tissues (acne vulgaris of medium severity, erysipelas, impetigo, secondarily infected dermatoses);
- uncomplicated urinary tract infections caused by Chlamydia trachomatis (urethritis and / or cervicitis);
- the initial stage of Lyme disease (borreliosis) - migrating erythema (erythema migrans).
The drug is taken orally 1 time / day for 1 hour before or 2 hours after eating, without chewing.
Adults and children over 12 years of age and weighing more than 45 kg
When infections of the upper and lower respiratory tract, ENT organs, with infections of the skin and soft tissues (except for chronic migrating erythema) , 500 mg / day for 1 reception for 3 days (exchange dose - 1.5 g).
For acne vulgaris of moderate severity - 500 mg 1 time / day for 3 days, then 500 mg once a week for 9 weeks; course dose - 6 g. The first weekly tablet should be taken 7 days after the first
daily tablet (the 8th day from the beginning of treatment), the subsequent 8 weekly tablets - with an interval of 7 days.
In acute infections of the urogenital organs (uncomplicated urethritis or cervicitis) - 1 g (2 tablespoons of 500 mg) once.
With Lyme disease (borreliosis) for the treatment of stage I (erythema migrans) - 1 g in day 1 and from 2 to 5 days - 500 mg daily (course dose - 3 g).
For treatment of patients older than 65 years , the same dose as for adults is used. Taking into account that among elderly patients there may be people with the presence of arrhythmogenic factors, it is necessary to pay special attention to the possibility of developing cardiac arrhythmia and ventricular pirouette tachycardia.
When violation of kidney function (CK more than 40 ml / min) dose adjustment is not required.
With a moderate violation of liver function, dose adjustment is not required.
The incidence of adverse reactions is represented by organ systems and according to the classification of the Medical Dictionary of Regulatory Activities (MedDRA): very frequent (> 10%), frequent (> 1% and <10%), infrequent (> 0.1% and <1 %), rare (> 0.01% and <0.1%), very rare (<0.01%), the frequency is unknown (it is not possible to determine the frequency of occurrence according to available data).
On the part of the hematopoiesis system: frequent - eosinophilia, lymphocytopenia; infrequent - leukopenia, neutropenia; rare thrombocytopenia, hemolytic anemia.
From the nervous system: frequent - headache, dizziness, paresthesia, a violation of taste sensations; infrequent - hypoesthesia, drowsiness, insomnia; very rare - anxiety, fainting, convulsions, psychomotor hyperactivity, loss of smell (or anosmia), perversion of smell, loss of taste sensations, myasthenia gravis.
From the side of the psyche: infrequent - increased excitability, insomnia; rare - agitation; frequency unknown - aggressiveness, anxiety, delirium, hallucinations.
From the side of the organ of vision: frequent - impaired vision.
From the side of the hearing organ and labyrinthine disorders: frequent - reversible hearing impairment up to deafness (with prolonged intake of high doses); infrequent - noise in the ears; rare - vertigo.
From the heart: infrequent - a feeling of heartbeat; very rare - prolongation of the QT interval, arrhythmia such as "pirouette", ventricular tachycardia.
From the side of the vessels: infrequent - the "tides" of blood to the face; frequency unknown - decrease in blood pressure.
From the gastrointestinal tract: very frequent - nausea, flatulence, diarrhea; frequent - abdominal pain, vomiting, indigestion; infrequent - constipation, gastritis, dysphagia, bloating, dryness of the oral mucosa, belching, ulcers of the oral mucosa, increased secretion of the salivary glands; very rare - change the color of the tongue.
From the endocrine system: very rare - pancreatitis.
From the side of the kidneys and urinary tract: infrequent - increased concentration of urea and creatinine in the blood plasma, dysuria, pain in the kidneys; very rare - interstitial nephritis, acute renal failure.
From the genitals and breast: infrequent - metrorrhagia, dysfunction of testicles.
From the immune system: infrequent - hypersensitivity reactions, angioedema; frequency unknown - anaphylactic reaction.
From the skin and subcutaneous tissues: frequent - itchy skin, skin rash; infrequent - photosensitization reaction, hives, Stevens-Johnson syndrome, dry skin, sweating; very rare - erythema multiforme, toxic epidermal necrolysis.
From the side of metabolism and nutrition: frequent - anorexia, a change in the concentration of potassium.
Infectious diseases: infrequent - candidiasis, incl. mucous membrane of the oral cavity and genitals, vaginal infections, pneumonia, fungal infections, bacterial infections, pharyngitis, gastroenteritis, respiratory diseases, rhinitis; frequency unknown - pseudomembranous colitis.
From the liver and biliary tract: infrequent - hepatitis; rare - a violation of liver function; very rare - cholestatic jaundice, liver failure (in rare cases with a fatal outcome, mainly on the background of severe violations of the liver function); liver necrosis, fulminant hepatitis.
From the musculoskeletal system and connective tissue: infrequent - osteoarthritis, myalgia, back pain, neck pain; frequency unknown - arthralgia.
From the respiratory system: infrequent - epistaxis, dyspnea.
General disorders and disorders at the site of administration: frequent - weakness; infrequent - chest pain, peripheral edema, asthenia, malaise, face swelling, fever.
On the part of laboratory indicators: frequent - an increase in the number of basophils, monocytes, neutrophils, a decrease or increase in the concentration of bicarbonates in the blood plasma; infrequent - increased activity of hepatic transaminases, increased bilirubin concentration in the blood plasma, increased activity of alkaline phosphatase, an increase in the level of chlorine in the blood plasma, an increase in the concentration of glucose in the blood plasma, an increase in the number of platelets, an increase in hematocrit, a change in the sodium content in the blood plasma.
- impaired hepatic function;
- impaired renal function of severe degree (CC <40 ml / min);
- the period of lactation (breastfeeding);
- Children under 12 years old with a body weight of less than 45 kg;
- simultaneous administration with ergotamine and dihydroergotamine;
- hypersensitivity to azithromycin, erythromycin, other macrolides, or ketolides, or other components of the drug.
With caution should be used in myasthenia gravis; violations of liver function of mild and moderate severity; violations of kidney function of mild and moderate severity (CK> 40 ml / min); at arrhythmias, the presence of pro-arrhythmic factors in patients with prolonged QT interval (congenital and acquired) or risk factors for QT prolongation (receiving antiarrhythmic drugs of classes IA, III, cisapride, hypokalemia or hypomagnesemia, clinically significant bradycardia or severe heart failure); with the simultaneous use of antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin, levofloxacin), cyclosporine, terfenadine, warfarin, digoxin; as well as elderly patients.
PREGNANCY AND LACTATION
The use of the drug during pregnancy is possible in the event that the intended use for the mother exceeds the potential risk to the fetus.
If it is necessary to use the drug during lactation, breastfeeding should be stopped.
APPLICATION FOR FUNCTIONS OF THE LIVER
The drug is contraindicated in cases of impaired renal function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated for violations of liver function.
APPLICATION FOR CHILDREN
It is used in children over 12 years of age and with a body weight of more than 45 kg.
If you miss a regular dose of Azithromycin Zentiva, the missed dose should be taken as soon as possible, and the subsequent dose should be taken at 24-hour intervals.
The drug Azithromycin Zentiva should be used at least 1 hour before and 2 hours after taking antacid preparations.
After the withdrawal of treatment, hypersensitivity reactions in some patients may persist, which requires specific therapy under the supervision of a physician.
The drug Azithromycin Zentiva should be used with caution in patients with mild to moderate liver function abnormalities 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, the drug should be discontinued and an examination of the functional state of the liver should be performed.
For mild to moderate renal impairment (CC> 40 mL / min), Azithromycin Zentiva should be administered with caution under the control of the kidney function. At the terminal stage of renal failure (CK <10 ml / min), the concentration of azithromycin in the blood plasma was increased by 33%.
Azithromycin is not a drug of choice for the prevention of pharyngitis / tonsillitis caused by Streptococcus pyogenes, and prevention of acute rheumatic fever.
As with the use of other antibacterial drugs, with the drug Azithromycin Zentiva should regularly monitor patients for the presence of resistant microorganisms and signs of development of superinfections, including. fungal.
The drug Azithromycin Zentiva should not be used for longer courses than indicated in the instructions, because pharmacokinetic properties of azithromycin allow us to recommend a short and convenient dosage regimen.
With prolonged use of Azithromycin Zentiva, the development of pseudomembranous colitis caused by Clostridium difficile, as in the form of mild diarrhea, and in the form of 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.
The syndrome of delayed repolarization of the ventricles (syndrome of prolongation of the interval QT) increases the risk of arrhythmias (including arrhythmias such as "pirouette") against the background of taking macrolides. Caution when using azithromycin should be observed in patients with prolonged QT interval receiving therapy with antiarrhythmic agents of classes IA, III, cisapride, hypokalemia or hypomagnesemia, clinically significant bradycardia, arrhythmia or severe heart failure.
The use of macrolides may provoke the development of myasthenic syndrome or cause an exacerbation of myasthenia gravis.
Impact on the ability to drive vehicles and manage mechanisms
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.
Symptoms: nausea, temporary loss of hearing, vomiting, diarrhea, abdominal pain, impaired liver function.
Treatment: gastric lavage, symptomatic therapy (reception of activated charcoal), control of vital functions.
Antacids (aluminum and magnesium-containing) slow down and reduce the absorption of azithromycin (for oral forms), so the interval between their intake should be 1 hour before or 2 hours after ingestion and these medications.
When combined, azithromycin does not affect the concentration of atorvastatin in the blood plasma, but there is a risk of rhabdomyolysis.
With the combined use of warfarin and azithromycin (in usual doses), no changes in prothrombin time have been detected, however, given the interaction between macrolides and warfarin, anticoagulant action may be enhanced, patients need to carefully monitor prothrombin time.
With the joint administration of digoxin and azithromycin, it is necessary to monitor the concentration of digoxin in the blood, many macrolides increase absorption of digoxin in the intestine, thereby increasing its concentration in the blood plasma.
If combined with cimetidine 2 hours before the administration of azithromycin, there is no effect on the pharmacokinetics of azithromycin.
When joint use of azithromycin with rifabutin should take into account the risk of developing neutropenia.
No data about the effect of azithromycin concentration in blood triazolam, midazolam, cimetidine, efavirenz, fluconazole, indinavir, trimethoprim / sulfamethoxazole in their joint application, but do not exclude the possibility of such interaction, as known macrolide interaction with the above drugs.
When the joint application of azithromycin with ergotamine or dihydroergotamine may enhance their toxic action (vasospasm, dysesthesia). No data on possible interactions between azithromycin and derivatives ergotamine and dihydroergotamine, but because of the development ergotism while the use of macrolides derivatives with ergotamine and dihydroergotamine combination data contraindicated.
Care must be taken in the combined use of terfenadine and azithromycin, since it has been found that simultaneous reception of terfenadine and various types of arrhythmia and antibiotics causes lengthening of the interval QT. On this basis, we can not exclude the above complications in the combined use of terfenadine, and azithromycin.
If necessary, the simultaneous application of cyclosporin is recommended to control the concentration of cyclosporine in the blood plasma. The simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times / day) causes an increase of the equilibrium concentration of azithromycin in plasma. No clinically significant side effects were observed and correction dose of azithromycin when applied simultaneously with nelfinavir not required.
While the use of zidovudine, azithromycin does not affect the pharmacokinetic parameters of plasma levels of zidovudine or its excretion by the kidneys and its glucuronide metabolite, but at the same time increases the concentration of the active metabolite - phosphorylated zidovudine - in mononuclear cells of peripheral blood vessels. The clinical
significance of this fact is not clear.
Azithromycin weakly interacts with the cytochrome P450 isozymes system. Not found that azithromycin is involved in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin is not an inducer and an inhibitor of cytochrome P450 isoenzymes.
In a joint application of azithromycin does not affect the concentration of drug in the blood plasma, carbamazepine, cimetidine, didanosine, efavirenz, fluconazole, indinavir, midazolam, theophylline, triazolam, cetirizine, trimethoprim / sulfamethoxazole, sildenafil, rifabutin and methylprednisolone.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.