Composition, form of production and packaging
Tablets covered with a film membrane of yellow color, capsular, biconvex; Two layers are visible on the cross-section, the inner layer is white or almost white.
1 tab.
azithromycin (in the form of dihydrate) 250 mg
Auxiliary substances: lactulose - 300 mg, calcium phosphate dihydrate - 59.8 mg, corn starch - 24 mg, hypromellose - 5 mg, sodium lauryl sulfate - 1.2 mg, croscarmellose sodium - 20 mg, magnesium stearate - 6 mg, microcrystalline cellulose - up to 700 mg .
The composition of the coating: (hypromellose 9.49 mg, titanium dioxide 5.2 mg, macrogol 4000 4.16 mg, talc 1.12 mg, tropeline-O 0.03 mg) up to 720 mg.
6 pcs. - packings of cellular contour (1) - packs cardboard.
Tablets covered with a film membrane of yellow color, capsular, biconvex; Two layers are visible on the cross-section, the inner layer is white or almost white.
1 tab.
azithromycin (in the form of dihydrate) 500 mg
Auxiliary substances: lactulose - 600 mg, calcium phosphate dihydrate - 119.6 mg, corn starch - 48 mg, hypromellose - 10 mg, sodium lauryl sulfate - 2.4 mg, croscarmellose sodium - 40 mg, magnesium stearate - 12 mg, microcrystalline cellulose - up to 1400 mg .
The composition of the shell: (hypromellose - 18.98 mg, titanium dioxide - 10.4 mg, macroline 4000 - 8.32 mg, talc - 2.24 mg, tropelin-O 0.06 mg) - up to 1440 mg.
3 pcs. - packings of cellular contour (1) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
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 the 50S subunit of the ribosome, it inhibits the peptidranslokase at the translation stage and suppresses 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 can initially be resistant to the action of an antibiotic or acquire resistance to it.
Microorganisms MIC, mg / l
Sensitive Resistant
Staphylococcus <1> 2
Streptococcus A, B, C, G <0.25> 0.5
Streptococcus pneumonia <0.25> 0.5
Haemophilus influenza <0.12> 4
Moraxella catarrhalis <0.5> 0.5
Neisseria gonorrhoeae <0.25> 0.5
In most cases, sensitive microorganisms:
1 . Gram-positive aerobes:
Staphylococcus aureus methicillin-sensitive
Streptococcus pneumoniae penicillin-sensitive
Streptococcus pyogenes
2. Gram-negative aerobes:
Haemophilus influenzae
Haemophilus parainfluenzae
Legionella pneumophila
Moraxella catarrhalis
Pasteurella multocida
Neisseria gonorrhoeae
3. Anaerobes:
Clostridium perfringens
Fusobacterium spp.
Prevotella spp.
Porphyromonas spp.
4. Other microorganisms:
Chlamydia trachomatis
Chlamydia pneumoniae
Chlamydia psittaci
Mycoplasma pneumoniae
Mycoplasma hominis
Borrelia burgdorferi
Microorganisms that can develop resistance to azithromycin
Streptococcus pneumoniae penicillin-resistant
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 is well absorbed and quickly distributed in the body. Bioavailability after a single dose of 500 mg - 37% (the effect of "first passage"), 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, binding to plasma proteins is inversely proportional to the concentration in the blood and leaves 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 is 10-50 times higher than in plasma, and the focus of infection is 24-34% higher than in healthy tissues.
Azithromycin has a very long T 1/2 - 35-50 h. T 1/2 of the tissues is much larger. The therapeutic concentration of azithromycin is maintained up to 5-7 days after the last dose.
Azithromycin is excreted, basically, in an 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;
- skin and soft tissue infections: common acne vulgaris, rye, impetigo, secondarily infected dermatitis;
- the initial stage of Lyme disease (borreliosis) - migrating erythema (erythema migrans);
- Urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis).
DOSING MODE
Ecomed В® is taken orally, without chewing, once a day, regardless of food intake. The drug is taken at least 1 hour before or 2 hours after a meal.
Adults (including the elderly) and children over 12 years of age with a body weight of over 45 kg
In infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues: 0.5 g / day for 3 days (course dose - 1.5 g).
For acne vulgaris of medium severity: 0.5 g / day for 3 days, then 0.5 g once a week for 9 weeks. 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. Course dose 6.0 g.
With migrating erythema: 1 time per day for 5 days, 1st day 1.0 g, then from 2nd to 5th day for 0.5 g. Course dose 3.0 g.
For infections of the urogenital tract caused by Chlamydia trachomatis (urethritis, cervicitis): 1.0 g once.
When used in patients with impaired renal function of mild severity, dose adjustment is not required.
When used in patients with impaired liver function of mild and moderate severity , in elderly patients dose adjustment is not required.
Elderly patients: dose adjustment is not required. Caution should be exercised in elderly patients with persistent pro-arrhythmic factors due to the high risk of arrhythmias, incl. arrhythmias of the "pirouette" type.
SIDE EFFECT
The incidence of adverse events is classified according to WHO recommendations: 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, incl. mucous membrane of the oral cavity and genitals, pneumonia, pharyngitis, gastroenteritis, respiratory diseases, rhinitis; an unknown frequency is pseudomembranous colitis.
From 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, dyspnoea, 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 disturbances: infrequently - hearing disorder, vertigo; unknown frequency - hearing impairment, incl. deafness and / or tinnitus.
From the side of the cardiovascular system: infrequently - a feeling of palpitations, flushes of blood to the face; unknown frequency - lowering blood pressure, increasing the QT interval on the ECG, arrhythmia such as "pirouette", ventricular tachycardia.
From the respiratory system: infrequently - shortness of breath, nosebleed.
From the digestive 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 biliary tract: infrequently - hepatitis; rarely - a violation of the liver, cholestatic jaundice; unknown frequency - hepatic insufficiency (in rare cases with a fatal outcome, mainly against a background of severe impairment of 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.
On the part of 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 kidneys; unknown frequency - interstitial nephritis, acute renal failure.
From the genitals and the breast: infrequently - metrorrhagia, dysfunction of the 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, an increase in the number of basophils, an increase in the number of monocytes, an increase in the number of neutrophils, a decrease in the concentration of bicarbonates in the blood plasma; infrequent increase in the activity of AST, ALT, increased bilirubin concentration in the blood plasma, increased urea concentration in the blood plasma, increased creatinine concentration in the blood plasma, a change in the potassium content in the blood plasma, increased activity of the AP in the 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 bicarbonate in the blood plasma, changing the sodium content in the blood plasma.
CONTRAINDICATIONS
- hypersensitivity to antibiotics of macrolides,
- hypersensitivity to other components of the drug;
severe hepatic impairment;
- severe renal failure (CC below 40 ml / min);
- Children under 12 years of age with a body weight of less than 45 kg (for this dosage form);
- breast-feeding;
- simultaneous administration with ergotamine and dihydroergotamine.
Carefully
- Myasthenia gravis;
- violations of liver function of mild and moderate severity;
- violations of the kidneys of mild and moderate severity (CC more than 40 ml / min);
- in patients with proarrhythmogenic factors (especially in elderly patients): with congenital or acquired prolongation of the QT interval, in patients receiving antiarrhythmic drugs of classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride,
terphenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with disturbances in the water-electrolyte balance, especially in the case of hypokalemia or
hypomagnesemia, with clinically significant bradycardia, cardiac arrhythmia or severe heart failure;
- simultaneous use of terfenadine, warfarin, digoxin,
cyclosporine.
PREGNANCY AND LACTATION
Azithromycin in pregnancy is recommended to be prescribed only in cases when the expected benefit from taking it for the mother exceeds the potential risk to the fetus.
During treatment with azithromycin, breastfeeding is suspended.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in severe renal failure.
If renal dysfunction of mild and moderate severity (CC is more than 40 ml / min), azithromycin therapy should be performed with caution under the control of the state of kidney function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in severe hepatic insufficiency.
The drug should be used with caution in patients with impaired liver function of mild and moderate severity 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.
APPLICATION FOR CHILDREN
This dosage form is contraindicated in children under 12 years of age with a body weight of less than 45 kg.
APPLICATION IN ELDERLY PATIENTS
Correction of the dose is not required. Caution should be exercised in elderly patients with persistent pro-arrhythmic factors due to the high risk of arrhythmias, incl.arrhythmias of the "pirouette" type.
SPECIAL INSTRUCTIONS
In case of missed intake of a single dose, the missed dose should be taken as soon as possible, and the subsequent dose with interruptions of 24 hours.
The drug should be taken at least 1 hour before or 2 hours after taking antacid preparations.
The drug should be used with caution in patients with impaired liver function of mild and moderate severity because of 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.
If renal dysfunction of mild and moderate severity (CC is more than 40 ml / min), azithromycin therapy should be performed with caution under the control of the state of kidney function.
As with the use of other antibacterial drugs, azithromycin should be regularly monitored for susceptible microorganisms and signs of development of superinfections, incl. number of fungal.
The drug should not be used for longer courses than indicated in the instructions, because 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 prolonged use of azithromycin, pseudomembranous colitis caused by Clostridium difficile can develop, both in the form of mild diarrhea and severe colitis. With the development of antibiotic-associated diarrhea against the background of taking the drug, and also after 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded.
When treating macrolides, incl. azithromycin, there was an increase in cardiac repolarization and QT interval, which increased the risk of cardiac arrhythmias, incl.arrhythmias of the "pirouette" type.
Caution should be exercised when using the drug in patients with proarrhythmogenic factors (especially in elderly patients): with congenital or acquired QT interval prolongation, in patients taking antiarrhythmic drugs of classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with disturbances in the water-electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, with 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.
Impact on the ability to drive vehicles and manage mechanisms
With the development of undesirable effects from the nervous system and the organs of vision, care should be taken when performing actions requiring increased concentration of attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: temporary loss of hearing, nausea, vomiting, diarrhea.
Treatment is symptomatic.
DRUG INTERACTION
Antacid preparations
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 1 hour before or 2 hours after taking these drugs and food.
Cetiruzen
Simultaneous use of azithromycin with cetirizine (20 mg) for 5 days in healthy volunteers did not lead to pharmacokinetic interaction and a significant change in the QT interval.
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, incl. azithromycin, with substrates of the P-glycoprotein, such as digoxin, leads to an increase in the concentration of the P-glycoprotein substrate in the 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
Simultaneous use of azithromycin (a single dose of 1000 mg and repeated administration of 1200 or 600 mg) has a slight effect on the pharmacokinetics, including.kidney removal of zidovudine or its glucuronide metabolite. However, the use of azithromycin caused an increase in the concentration of 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 is involved in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin 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
Simultaneous use of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause changes atorvastatin concentrations in plasma (based on analysis of the inhibition of HMG-CoA reductase). However, in the post-registration period, some were reported cases of rhabdomyolysis in patients receiving both azithromycin and statins.
Karbamazepii
In pharmacokinetic studies in healthy volunteers did not reveal a significant impact on the concentration of carbamazepine and its active metabolite in the blood plasma of patients treated with azithromycin at the same time.
cimetidine
The pharmacokinetic studies a single dose of cimetidine effect on the pharmacokinetics of azithromycin is not revealed changes pharmacokinetics of azithromycin provided use of cimetidine for 2 hours to azithromycin.
Indirect anticoagulants (coumarin derivatives)
In pharmacokinetic studies of azithromycin had no effect on the anticoagulant effect of a single dose of 15 mg of warfarin in healthy volunteers received. It has been reported to potentiate the anticoagulant effect after simultaneous application of azithromycin and indirect anticoagulants (coumarin derivatives). Despite the fact that a causal link has not been established, it is necessary to take into account the need for frequent monitoring of PV in the application of azithromycin in patients receiving oral anticoagulants of indirect action (coumarin derivatives).
Cyclosporin
In pharmacokinetic study involving healthy volunteers for 3 days ingested azithromycin (500 mg / day one), and then the cyclosporin (10 mg / kg / day once) revealed a significant increase in Cmax in the blood plasma and the AUC 0-5 cyclosporine. Caution must be exercised while the use of these drugs. If necessary, the simultaneous use of these drugs need to be monitored in the blood plasma concentration of cyclosporine and adjust the dose.
Efavirenz
simultaneous use of azithromycin (600 mg / day one) and efavirenz (400 mg / day) daily for 7 days did not cause any clinically significant pharmacokinetic interaction.
Fluconazole
simultaneous use of azithromycin (1200 mg single dose) did not alter the pharmacokinetics of fluconazole (800 mg dose). Total exposure and T 1/2azithromycin is not changed while the application of fluconazole, however, the observed decrease in C max of azithromycin (18%), which had no clinical significance.
Indinavir
simultaneous use of azithromycin (1200 mg single dose) had no statistically significant effect on the pharmacokinetics of indinavir (800 mg 3 times / day for 5 days).
Methylprednisolone
Azithromycin has no significant effect on the pharmacokinetics of methylprednisolone.
Nelfinavir
simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times / day) causes an increase in C ssazithromycin in serum. No clinically significant side effects were not observed, and correction dose of azithromycin when applied simultaneously with nelfinavir not required.
Rifabutin
simultaneous use of azithromycin and rifabutin is not affected by the concentration of each drug in the serum. With simultaneous use of azithromycin and rifabutin sometimes observed neutropenia. Despite the fact that neutropenia 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 not received proof effect of azithromycin (500 mg / day, daily for 3 days) on the AUC and C maxsildenafil or its main circulating metabolite.
Terfenadine
In pharmacokinetic studies were not obtained evidence interactions between azithromycin and terfenadine. It reported a few cases, when the possibility of such an interaction could not be excluded completely, but there was no specific evidence that such an interaction has taken place. It has been found that the simultaneous use of terfenadine and macrolides can cause arrhythmia and lengthening the interval QT.
Theophylline
There was no interaction between azithromycin and theophylline.
Truazolam / mudazolam
Significant changes pharmacokinetic parameters, while the application of azithromycin with midazolam or triazolam in therapeutic doses were not identified.
Trimethoprim / sulfamethoxazole
simultaneous use of trimethoprim / sulfamethoxazole with azithromycin showed no significant effect on C max , the overall exposure or excretion by the kidneys trimethoprim or sulfamethoxazole. The concentration of azithromycin in blood serum consistent with detectable in other studies.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
Store in a dry, dark place at a temperature of no higher than 25 В° C. Keep out of the reach of children. Shelf life - 2 years. Do not use after the expiration date.
