Instructions for Azithromycin
On 1 tablet of 500 mg
Active ingredient: azithromycin dihydrate - 531.00 mg, in terms of azithromycin - 500.0 mg.
Excipients (core): microcrystalline cellulose - 240.00 mg, pregelatinized starch - 100.00 mg, croscarmellose sodium - 20.00 mg, magnesium stearate - 9.00 mg.
Auxiliary substances (shell): opadry II 85F48105 White - 30.00 mg, incl. polyvinyl alcohol - 14.07 mg, macrogol 3350 - 7.08 mg, talc - 5.22 mg, titanium dioxide - 3.63 mg.
After oral administration, azithromycin is well absorbed and quickly distributed in the body. After a single dose of 500 mg, bioavailability is 37% (the effect of "primary passage"), the maximum plasma concentration (C max) - 0.4 mg / l is created after 2-3 hours, the volume of distribution - 31 l / kg.
Binding to plasma proteins is inversely proportional to the concentration in the blood and is 7-50%. It penetrates cell membranes (effective for infections caused by intracellular pathogens).
Transported by phagocytes, polymorphonuclear leukocytes and macrophages to the site of infection, where it is released in the presence of bacteria.
Easily passes through histohematogenous barriers and enters the tissue. Concentration in tissues and cells is 10-50 times higher than in blood plasma, and in the focus of infection - by 24-34% more than in healthy tissues.
The half-life is 35-50 hours. The half-life of tissues is much longer. The therapeutic concentration of azithromycin is maintained for up to 5-7 days after the last dose.
Azithromycin is excreted mainly in unchanged form - 50% of the intestine, 6% of the kidneys. In the liver it is demethylated, losing activity.
- Infectious and inflammatory diseases caused by microorganisms sensitive to azithromycin:
- 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, including caused by atypical pathogens);
- Infections of the skin and soft tissues (common acne of moderate severity, erysipelas, impetigo, and secondarily infected dermatosis);
- The initial stage of Lyme disease (borreliosis)
- erythema migrans (erythema migrans);
- Uncomplicated urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis).
Azithromycin is a broad-spectrum bacteriostatic from the group of macrolide-azalides.
It has a wide range of antimicrobial action. The mechanism of action of azithromycin is associated with the suppression of microbial cell protein synthesis.
Binding to the 50S subunit of the ribosomes of bacterial cells, inhibits peptide translocation at the translation stage and inhibits protein synthesis, slowing the growth and reproduction of bacteria. In high concentrations has a bactericidal effect.
It has activity against a number of gram-positive, gram-negative, anaerobic, intracellular and other microorganisms.
Microorganisms may initially be resistant to the action of the or may become resistant to it.
Sensitive: aerobic gram-positive microorganisms - Staphylococcus aureus (methicillin-sensitive), Streptococcus pneumoniae (penicillin-sensitive), Streptococcus pyogenes, Streptococcus group A, B, C, G; aerobic gram-negative microorganisms - Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis, Pasteurella multocida, Neisseria gonorrhoeae; anaerobic microorganisms — Clostridium perfringens, Fusobacterium spp., Prevotella spp., Porphyromonas spp .; others - Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi. Microorganisms capable of developing azithromycin resistance: Gram-positive aerobes are Streptococcus pneumoniae (penicillin-resistant strains).
Natural resistance microorganisms: Gram-positive aerobes - Enterococcus faecalis, Staphylococcus spp. (methicillin-resistant strains); anaerobes - Bacteroides fragilis. Cases of cross-resistance of Streptococcus pneumoniae, Streptococcus pyogenes (beta-hemolytic streptococcus group A), Enterococcus faecalis, and Staphylococcus aureus, including Staphylococcus aureus (methicillin-resistant strains) to erythromycin, azythyromatitis, azythyrophyrosis, aythyroid syndrome, azythyromatitis, Erythrophytesis, erythromycin, and antiarrhythmias are described.
Azithromycin Side Effects:
The frequency of side effects is classified according to the recommendations of the World Health Organization: very often - at least 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% (including isolated cases).
Infectious diseases: infrequently - candidiasis, including the mucous membrane of the oral cavity and genitalia, pneumonia, pharyngitis, gastroenteritis, respiratory diseases, rhinitis; very rarely - pseudomembranous colitis.
From the side of blood and lymphatic system: often - eosinophilia, lymphopenia, basophilia, monocytosis, increase in the number of neutrophils; infrequently - leukopenia, neutropenia; very rarely - thrombocytopenia, hemolytic anemia. Metabolism and nutrition: often - anorexia.
Allergic reactions: often - pruritus, skin rash; infrequently - hypersensitivity reactions, photosensitivity reactions, dermatitis, dry skin, sweating, urticaria, Stevens-Johnson syndrome, angioedema; very rarely - anaphylactic reaction, erythema multiforme, toxic epidermal necrolysis.
From the nervous system: often - headache, dizziness, paresthesia, impaired taste sensations; infrequently - hypoesthesia, drowsiness, insomnia, nervousness, agitation; very rarely - anxiety, aggression, fainting, convulsions, psychomotor hyperactivity, loss of smell (or anosmia) and taste, perversion of smell, myasthenia, delusions, hallucinations.
On the part of the organ of hearing and labyrinth disorders: often - hearing loss, deafness; infrequently - tinnitus; rarely - vertigo. On the part of the organ of vision: often - a violation of clarity of vision. Since the cardiovascular system: infrequently - a sensation of heartbeat, "flush" of blood to the face; very rarely, a decrease in blood pressure, an increase in the QT interval on an electrocardiogram, a pirouette-type arrhythmia, and ventricular tachycardia.
On the part of the respiratory system: infrequently - shortness of breath, epistaxis. On the part of the gastrointestinal tract: very often - nausea, diarrhea, abdominal pain, flatulence; often - dyspepsia, vomiting; infrequently - constipation, gastritis, dysphagia, bloating, dryness of the oral mucosa, belching, ulcers of the oral mucosa, increased salivary gland secretion; very rarely - change the color of the tongue, pancreatitis.
On the part of the liver and biliary tract: infrequently - increased activity of "liver" transaminases, increasing the concentration of bilirubin, hepatitis; rarely, liver dysfunction, cholestatic jaundice; very rarely - liver failure (in rare cases with a fatal outcome, mainly due to severe liver dysfunction); liver necrosis, fulminant hepatitis.
On the part of the musculoskeletal system and connective tissue: infrequently - osteoarthritis, myalgia, back pain, neck pain; very rarely - arthralgia. On the part of the kidneys and urinary tract: infrequently - dysuria, pain in the kidneys, increasing the concentration of urea and creatinine in the blood plasma; very rarely - interstitial nephritis, acute renal failure.
From the genital organs and mammary glands: infrequently - metrorrhagia, dysfunction of the testicles. Laboratory indicators: often - a decrease in plasma bicarbonate concentration; Infrequently, a change in plasma concentration of potassium, an increase in alkaline phosphatase activity, an increase in plasma chlorine and glucose concentrations, an increase in platelet count, an increase in hematocrit, an increase in bicarbonate concentration, and a change in plasma sodium concentration.
Other: infrequently - asthenia, malaise, feeling tired, swelling of the face, chest pain, peripheral edema, fever.
Special conditions Azithromycin:
In case of missing a single dose of Azithromycin, the missed dose should be taken as early as possible, and the next dose should be taken 24 hours apart. Azithromycin should be taken at least 1 hour before or 2 hours after taking antacid medications. A drug
Azithromycin should be used with caution in patients with mild to moderate hepatic impairment due to the possibility of the development of fulminant hepatitis and severe liver failure. If there are symptoms of abnormal liver function, such as rapidly increasing asthenia, jaundice, dark urine, bleeding tendency, hepatic encephalopathy, therapy with Azithromycin should be stopped and a study of the functional state of the liver should be carried out. In case of impaired renal function of mild and moderate severity (CC more than 40 ml / min), azithromycin therapy should be carried out with caution under the control of the state of kidney function.
It must be remembered that for the prevention of pharyngitis / tonsillitis caused by Streptococcus pyogenes, as well as for the prevention of acute rheumatic fever, penicillin is usually the drug of choice. As with the use of other antibacterial drugs, with Azithromycin therapy, patients should be regularly examined for the presence of refractory microorganisms and signs of the development of superinfection, including fungal ones.
The drug Azithromycin should not be used for longer courses than indicated in the instructions, since the pharmacokinetic properties of azithromycin allow us to recommend a short and convenient dosage regimen. There is no data on the possible interaction between azithromycin and ergotamine and dihydroergotamine derivatives, but due to the development of ergotism with the simultaneous use of macrolides with ergotamine and dihydroergotamine derivatives, this combination is contraindicated. diarrhea and severe colitis.
With the development of diarrhea in the presence of azithromycin, as well as 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded.
In mild cases, it is enough to cancel azithromycin and use ion-exchange resins (Kolestiramine, Colestipol), in severe cases, it is shown to compensate for the loss of fluid, electrolytes and protein, the appointment of vancomycin or metronidazole. Do not use drugs that inhibit intestinal peristalsis.
The syndrome of delayed ventricular repolarization - a syndrome of lengthening the QT interval - increases the risk of developing arrhythmias, including pirouette-type arrhythmias while taking macrolides, and also Azithromycin.
Caution should be exercised when using azithromycin in patients with pro-arrhythmogenic factors (especially in elderly patients), including congenital or acquired prolongation of the QT interval: in patients receiving therapy with antiarrhythmic agents of classes IA (quinidine, procainamide) III (dofetidil, amiodarone , sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin, levofloxacin), in patients with impaired water and electrolyte balance, Aubin in the case of hypokalemia or hypomagnesemia, clinically significant bradycardia, cardiac arrhythmia or severe heart failure. The use of azithromycin may trigger the development of myasthenic syndrome or cause exacerbation of myasthenia. Influence on ability to drive vehicles and work with mechanisms
With the development of undesirable effects on the part of the nervous system and the organ of vision, care should be taken when performing actions that require increased concentration and psychomotor speed.
Hypersensitivity to azithromycin, other macrolides or ketolides, or other components of the drug; severe liver dysfunction (Child-Pugh class C); severe renal dysfunction (CC less than 40 ml / min); children's age up to 12 years with a body weight less than 45 kg (for tablets 500 mg); children's age up to 3 years (for tablets of 125 mg); breastfeeding period; concomitant use with ergotamine and dihydroergotamine. Carefully:
Myasthenia gravis; liver dysfunction mild to moderate severity; impaired renal mild and moderate severity (CC more than 40 ml / min); arrhythmia, in the presence of pro-arrhythmogenic factors (especially in elderly patients), including congenital or acquired lengthening of the QT interval; in patients receiving therapy with antiarrhythmic drugs of classes IA (quinidine, procainamide), III (dofetidil, amiodarone, sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin, Ivo, Ivo, Ivo, Ivo, Ivo, Ivo, Ivo, Ivo, Ivo, Ivo, Imoxifloxacin, Izo, Imoxifloxin, Imoxifloxin, Imoxifloxin, Imoxifloxinum water-electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, clinically significant bradycardia, severe heart failure; simultaneous use of warfarin, digoxin, cyclosporine. Pregnancy and lactation:
Use of the drug during pregnancy is possible only in cases where the intended benefit to the mother outweighs the potential risk to the fetus.
If necessary, the use of the drug during lactation should decide on the termination of breastfeeding.
Drug Interactions Azithromycin:
Antacid drugs do not affect the bioavailability of azithromycin, but reduce the maximum concentration of azithromycin in the blood by 30%, so azithromycin should be taken 1 hour before or 2 hours after taking antacids. Simultaneous use of azithromycin with cetirizine (20 mg) in healthy volunteers for 5 days did not lead to a pharmacokinetic interaction and a significant change in the QT interval.
The simultaneous use of azithromycin (1200 mg / day) and didanosine (400 mg / day) in 6 HIV-infected patients showed no changes in the pharmacokinetic parameters of didanosine compared with the placebo group.
The simultaneous use of macrolide antibacterial drugs, including azithromycin, with P-glycoprotein substrates, such as digoxin, leads to an increase in the concentration of P-glycoprotein substrate in the blood plasma. Thus, with simultaneous use of digoxin and azithromycin, it is necessary to consider the possibility of increasing the concentration of digoxin in the blood plasma.
Simultaneous use of azithromycin (a single dose of 1000 mg and repeated administration of 1200 mg or 600 mg) has a slight effect on the pharmacokinetics, including kidney excretion, zidovudine or its glucuronide metabolite. However, the concentration of the active metabolite, phosphorylated zidovudine, increases in peripheral blood mononuclear cells.
The clinical significance of this fact is unclear. Azithromycin poorly interacts with cytochrome P450 isoenzymes. It has not been 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. Given the theoretical possibility of the development of ergotism, simultaneous use of azithromycin with ergot alkaloid derivatives (ergotamine, dihydroergotamine) is not recommended. Pharmacokinetic studies of the simultaneous use of azithromycin and drugs, the metabolism of which occurs with the participation of cytochrome P450 isoenzymes, were conducted.
Atorvastatin: simultaneous use of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause changes in plasma concentrations of atorvastatin (based on the HMG-CoA reductase inhibition assay). However, there have been reports of cases of rhabdomyolysis in patients receiving both azithromycin and statins. Carbamazepine: in pharmacokinetic studies involving healthy volunteers, no significant effect was found on the concentration of carbamazepine and its active metabolite in blood plasma, while using azithromycin. Cimetidine:
in pharmacokinetic studies of the effect of a single dose of cimetidine on azithromycin pharmacokinetics, no changes in azithromycin pharmacokinetics were detected, provided that cimetidine was used 2 hours before azithromycin.
Indirect anticoagulants (coumarin derivatives): In pharmacokinetic studies, azithromycin did not affect the anticoagulant effect of warfarin in a single dose of 15 mg taken by healthy volunteers.
The potentiation of the anticoagulant effect has been reported after the simultaneous use of azithromycin and indirect anticoagulants (coumarin derivatives).
Despite the fact that a causal relationship has not been established, it is recommended that careful monitoring of prothrombin time in patients is recommended, while azithromycin and indirect anticoagulants (coumarin derivatives) should be used simultaneously.
Cyclosporine: in pharmacokinetic studies involving healthy volunteers who took azithromycin orally for 3 days (500 mg / day once) and then cyclosporine (10 mg / kg / day once), a significant increase in the maximum plasma concentration and under the concentration-time curve of cyclosporine.
Caution should be exercised with the simultaneous use of these drugs. If necessary, the simultaneous use of these drugs, it is necessary to monitor the concentration of cyclosporine in the blood plasma and adjust the dose accordingly.
Efavirenz: simultaneous use of azithromycin (600 mg / day once) and efavirenz (400 mg / day) daily for 7 days did not cause any clinically significant pharmacokinetic interaction. Fluconazole: co-administration of azithromycin (1200 mg once) did not change the pharmacokinetics of fluconazole (800 mg once). The total exposure and half-life did not change with the simultaneous use of fluconazole, however, they noted a decrease in the maximum concentration of 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 has no significant effect on the pharmacokinetics of methylprednisolone. Nelfinavir: simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg three times a day) causes an increase in the equilibrium concentration of azithromycin in the blood plasma.
No clinically significant adverse effects were observed and dose adjustment of azithromycin, when used simultaneously with nelfinavir, is not required. Rifabutin: the simultaneous use of azithromycin and rifabutin does not affect the concentration of each of the drugs in the blood plasma.
With simultaneous use of azithromycin and rifabutin, neutropenia has sometimes been 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, there is no evidence of the effect of azithromycin (500 mg / day daily for 3 days) on the maximum plasma concentration and area under the concentration-time curve of sildenafil and its main metabolite. Terfenadine: In pharmacokinetic studies, no evidence of interaction between azithromycin and terfenadine was obtained.
It was reported on isolated cases where the possibility of such an interaction could not be completely excluded, but there was no concrete evidence that such an interaction had taken place. It was found that the simultaneous use of terfenadine and macrolide-class causes arrhythmia and prolongation of the QT interval.
Theophylline: no interaction between azithromycin and theophylline was detected. Triazolam / midazolam: There were no significant changes in pharmacokinetic parameters with simultaneous use of azithromycin with triazolam or midazolam at therapeutic doses.
Trimethoprim / sulfamethoxazole: the simultaneous use of trimethoprim / sulfamethoxazole with azithromycin did not reveal a significant effect on the maximum concentration, total exposure or excretion of trimethoprim or sulfamethoxazole by the kidneys. Plasma azithromycin concentration was consistent with that found in other studies.
Inside, without chewing, once a day, at least 1 hour before or 2 hours after meals. Adults and children over 12 years old with a body weight over 45 kg.
For infections of the upper and lower respiratory tract, upper respiratory tract, skin and soft tissues: 500 mg 1 time a day for 3 days (course dose 1.5 g). The initial stage of Lyme disease: 1 time per day for 5 days: 1st day - 1000 mg, then from 2nd to 5th day - 500 mg each (course dose 3.0 g).
In urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis): uncomplicated urethritis / cervicitis - 1000 mg once.
Common acne moderate severity: course dose is 6 g: 500 mg 1 time per day for 3 days, then 500 mg 1 time per week for 9 weeks. The first weekly pill should be taken 7 days after taking the first daily pill (8th day from the start of treatment), the next 8 weekly pills - with an interval of 7 days.
Children aged 3 to 12 years with a body weight less than 45 kg.
For infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues: at the rate of 10 mg / kg body weight 1 time per day for 3 days (course dose 30 mg / kg). For pharyngitis / tonsillitis caused by Streptococcus pyogenes: At the rate of 20 mg / kg / day for 3 days (course dose 60 mg / kg). The maximum daily dose is 500 mg.
Initial Lyme Disease:
On the 1st day - at a dose of 20 mg / kg of body weight 1 time per day, then from 2 to 5th day - daily at a dose of 10 mg / kg body weight 1 time per day (course dose 60 mg / kg).
In case of impaired renal function: in patients with impaired renal function of mild and moderate severity (CC more than 40 ml / min) dose adjustment is not required.
In case of impaired liver function: in case of impaired liver function, mild and moderate severity does not require dose adjustment Elderly patients: dose adjustment is not required.
Since older people may have pro-arrhythmic conditions, care should be taken when using the drug, due to the high risk of developing cardiac arrhythmias, including pirouette-type arrhythmias.
temporary hearing loss, nausea and vomiting, diarrhea. Treatment: symptomatic.