Azithromycin pills 500 mg, 3 pcs. – Biochemist

Composition

Active ingredient: 500 mg (respectively for each dose) of azithromycin dihydrate – 524,0 mg (in terms of azithromycin) – 500,0 mg;excipients of the tablet core: cellulose microcrystalline (type 101) is 122,0 mg, cellulose microcrystalline (type 12) – 16,0 mg, corn starch pregelatinization – 100,0 mg, croscarmellose sodium – 20,0 mg, magnesium stearate – 9.0 mg, talc – 9.0 mg, the weight of the tablet core – 900,0 mg;excipients film shell: hypromellose USD 11.8 mg, macrogol (polyethylene glycol) 6000 and 4.6 mg titanium dioxide – 1,86 mg, Polysorbate 80 to 1.74 mg; mass of tablet, film-coated 920,0 mg

Pharmacological action

Azithromycin is a broad-spectrum bacteriostatic 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 microbial cell protein synthesis. Binding to the 50S ribosomal subunit of bacterial cells, it inhibits peptidtranslase at the translation stage and suppresses protein synthesis, slowing down the growth and reproduction of bacteria. In high concentrations, it has a bactericidal effect. It is active against a number of gram-positive, gram-negative, anaerobic, intracellular and other microorganisms. Microorganisms may initially be resistant to the action of an antibiotic or may become resistant to it. Scale of sensitivity of microorganisms to azithromycin (Minimum inhibitory concentration (MIC), mg / l)In most cases, sensitive microorganisms:1. Gram-positive Staphylococcus aureus aerobes (methicillin-sensitive strains)Streptococcus pneumoniae (penicillin-sensitive strains)Streptococcus pyogenes2. Gram-negative aerobes: Haemophilus influenzaeHaemophilus parainfluenzaeLegionella pneumophilaMoraxella catarrhalisPasteurella multocidaNeisseria gonorrhoeae3. AnaerobesClostridium perfringensFusobacterium spp. Prevotella spp. Porphyromonas spp.4. Other microorganisms Chlamydia trachomatisChlamydia pneumoniaChlamydia psittaciMycoplasma pneumoniaeMycoplasma hominisBorrelia Burgdorferi Microorganisms capable of developing resistance to azithromycin: Gram-positive aerobesstreptococcus pneumoniae (penicillin-resistant strains)Initially resistant microorganisms:Gram-positive aerobesenterococcus faecalis staphylococcus spp. (methicillin-resistant strains of staphylococcus with a very high frequency have acquired resistance to macrolides)Gram-positive bacteria resistant to erythromycin. Anaerobes of Acteroides fragilis. Pharmacokineticsabsorption: After oral administration, azithromycin is well absorbed and quickly distributed in the body. After a single 500 mg dose, the bioavailability is 37% (due to the “first pass” effect through the liver). The maximum concentration (0.4 mg/l) in the blood is created after 2-3 hours. Distribution: The apparent volume of distribution is 31.1 l / kg, protein binding is inversely proportional to the blood concentration and is 7-50%. Penetrates 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 penetrates through histohematic barriers and enters the tissues. The concentration of azithromycin in tissues and cells is 10-50 times higher than in blood plasma, and in the focus of infection-24-34% higher than in healthy tissues. Metabolism: Azithromycin is demethylated in the liver, losing its activity. Deduction: Azithromycin has a very long half-life of 35-50 hours. The tissue half-life is significantly longer. The therapeutic concentration of azithromycin is maintained up to 5-7 days after the last dose. Azithromycin is mainly excreted unchanged-50% through the intestines,6% by the kidneys.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug:- Upper respiratory tract and ENT infections (pharyngitis/tonsillitis, sinusitis, otitis media);- Lower respiratory tract infections: acute bronchitis, exacerbation of chronic bronchitis, pneumonia, including those caused by atypical pathogens; – Skin and soft tissue infections (acne vulgaris of moderate severity, erysipelas, impetigo, secondary infected dermatoses);- Initial stage of Lyme disease (borreliosis) – erythema migrans (erythema migrans); – Urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis).

Use during pregnancy and lactation

During pregnancy and lactation, it is used only if the intended benefit to the mother exceeds the potential risk to the fetus and child. If it is necessary to use the drug during breastfeeding, it is recommended to suspend breastfeeding.

Contraindications

Hypersensitivity to azithromycin, erythromycin, other macrolides or ketolides, or other components of the drug; severe hepatic impairment; children under 12 years of age with a body weight of less than 45 kg (for 500 mg and 250 mg tablets); children under 3 years of age (for 125 mg tablets); simultaneous administration with ergotamine and dihydroergotamine. With caution, myasthenia gravis; mild to moderate hepatic impairment; end-stage renal failure with GFR (glomerular filtration rate) less than 10 ml / min; in patients with proarrhythmogenic factors (especially in elderly patients): patients with congenital or acquired prolongation of the QT interval, in patients receiving therapy with antiarrhythmic drugs of classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with impaired water and oxygen balance. 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.

Side effects

the Frequency of side effects is classified in accordance with the recommendations of the world health organization: very often – at least 10%; often – not less than 1% but < 10%; infrequently – no more than 0.1% but < 1%; rarely – not less than 0.01%, but less than 0.1%; very rarely – less than 0.01%; frequency unknown – cannot be determined based on available data. Infectious diseases: infrequently-candidiasis, including oral mucosa, vaginal infection, pneumonia, fungal infection, bacterial infection, pharyngitis, gastroenteritis, respiratory diseases, rhinitis; unknown frequency-pseudomembranous colitis. Blood and lymphatic system disorders: 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. Nervous system disorders: often-headache; infrequently-dizziness, impaired taste sensations, paresthesia, drowsiness, insomnia, nervousness; rarely-agitation; unknown frequency-hypesthesia, anxiety, aggression, fainting, convulsions, psychomotor hyperactivity, loss of sense of smell, perversion of smell, loss of taste sensations, myasthenia gravis, delirium, hallucinations. From the side of the visual organ: infrequently-visual impairment. Hearing disorders and labyrinth disorders: infrequently – hearing disorder, vertigo; unknown frequency – hearing impairment, including deafness and / or tinnitus. From the cardiovascular system: infrequently-palpitation of the heart, “flushes” of blood to the face; unknown frequency-lowering of blood pressure, increase in the QT interval on the electrocardiogram, arrhythmia of the “pirouette” type, ventricular tachycardia. Respiratory system disorders: infrequently-shortness of breath, nosebleeds. From the gastrointestinal tract: very often – diarrhea; often-nausea, vomiting, abdominal pain; infrequently-flatulence, dyspepsia, constipation, gastritis, dysphagia, bloating, dry oral mucosa, belching, ulcers of the oral mucosa, increased salivary gland secretion; very rarely – discoloration of the tongue, pancreatitis. Liver and biliary tract disorders: infrequently-hepatitis; rarely-liver dysfunction, cholestatic jaundice; unknown frequency-liver failure (in rare cases-with a fatal outcome, mainly against the background of severe liver dysfunction); liver necrosis, fulminant hepatitis. Skin and subcutaneous tissue disorders: infrequently-skin rash, pruritus, urticaria, dermatitis, dry skin, sweating; rarely-photosensitization reaction; unknown frequency-Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug rash with eosinophilia and systemic manifestations (DRESS-syndrome). 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 area; unknown frequency-interstitial nephritis, acute renal failure. From the genitals and breast: infrequently – metrorrhagia, testicular dysfunction. Other services: infrequently – edema, asthenia, malaise, fatigue, facial 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 blood plasma; infrequently – an increase in the activity of aspartate aminotransferase, alanine aminotransferase, an increase in the concentration of bilirubin in blood plasma, an increase in the concentration of urea in blood plasma, an increase in the concentration of creatinine in blood phosphatases in blood plasma, increased chloride content in blood plasma, increased glucose concentration in blood, increased platelet count, decreased hematocrit, increased bicarbonate concentration in blood plasma, changes in sodium content in blood plasma.

Interaction

Antacid preparations Antacid preparations 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 eating. Cetirizine Simultaneous administration 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 QT interval. Didanosine (dideoxyinosine)Concomitant use of azithromycin (1200 mg / day) and didanosine (400 mg / day) In 6 HIV-infected patients, there were no changes in the pharmacokinetic indications of didanosine compared to the placebo group. Digoxin (P-glycoprotein substrates)Concomitant use of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates, such as digoxin, leads to an increase in the concentration of the P-glycoprotein substrate in the blood serum. Thus, when using digoxin and azithromycin simultaneously, it is necessary to take into account the possibility of increasing the concentration of digoxin in the blood serum. Zidovudine Simultaneous administration of azithromycin (a single dose of 1000 mg and multiple doses of 1200 mg or 600 mg) has little effect on the pharmacokinetics, including renal excretion 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 cytochrome P450 isoenzymes. Azithromycin has not been shown to be involved in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin is not an inhibitor or inducer of cytochrome P450 isoenzymes. Ergot Alkaloidsaccepting the theoretical possibility of ergotism, simultaneous use of azithromycin with ergot alkaloid derivatives is contraindicated. Pharmacokinetic studies were conducted on the concomitant use of azithromycin and drugs that are metabolized with the participation of cytochrome P450 enzymes. Simultaneous administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause changes in plasma concentrations of atorvastatin (based on the analysis of MMC-CoA reductase inhibition). However, in the acute marketing period, there have been isolated reports of rhabdomyolysis in patients receiving concomitant azithromycin and statins. CarbamazepinE pharmacokinetic studies in healthy volunteers did not reveal a significant effect on the concentration of carbamazepine and its active metabolite in blood plasma in patients receiving azithromycin at the same time. CimetidinE In pharmacokinetic studies of the effect of a single dose of cimetidine on the pharmacokinetics of azithromycin, there were no changes in the pharmacokinetics of azithromycin, provided that cimetidine was used 2 hours before azithromycin. Indirect anticoagulants (coumarin derivatives)In pharmacokinetic studies, azithromycin did not affect the anticoagulant effect of a single dose of 15 mg of warfarin taken in healthy volunteers. Potentiation of the anticoagulant effect has been reported after concomitant administration of azithromycin and indirect anticoagulants (coumarin derivatives). Although no causal relationship has been established, the need for frequent monitoring of prothrombin time should be considered when using azithromycin in patients receiving oral indirect anticoagulants (coumarin derivatives). Cyclosporin In a pharmacokinetic study involving healthy volunteers who took azithromycin (500 mg/day once) and then cyclosporin (10 mg/kg/day once) orally for 3 days, a significant increase in the maximum concentration in blood plasma (Cmax) and the area under the concentration-time curve (AUC0-5) of cyclosporin was revealed. Caution should be exercised when using these drugs simultaneously. If simultaneous use of these drugs is necessary, it is necessary to monitor the concentration of cyclosporine in blood plasma and adjust the dose accordingly. Simultaneous administration of azithromycin (600 mg / day once) and efavirenz (400 mg/day) daily for 7 days did not cause any clinically significant pharmacokinetic interaction. Simultaneous administration of azithromycin (1200 mg once) did not alter the pharmacokinetics of fluconazole (800 mg once). The total exposure and half-life of azithromycin did not change with concomitant use of fluconazole, but there was a decrease in the Cmax of azithromycin (by 18%), which was not clinically significant. Indinavir Simultaneous administration 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). Methylprednisolonazithromycin has no significant effect on the pharmacokinetics of methylprednisolone. Simultaneous administration of azithromycin (1200 mg) and nelfinavir (750 mg 3 times a day) causes an increase in the steady-state concentration of azithromycin in the blood serum. No clinically significant side effects were observed and no dose adjustment of azithromycin is required when co-administered with nelfinavir. Rifabutin Simultaneous use of azithromycin and rifabutin does not affect the concentration of each of the drugs in the blood serum. Neutropenia has sometimes been observed with concomitant use of azithromycin and rifabutin. Although neutropenia has been associated with rifabutin use, a causal relationship between the use of azithromycin and rifabutin combination and neutropenia has not been established. Sildenafil When used in healthy volunteers, there was no evidence of the effect of azithromycin (500 mg / day daily for 3 days) on the AUC and Cmax of sildenafil and its main circulating metabolite. TerfenadinE In pharmacokinetic studies, there was no evidence of an interaction between azithromycin and terfenadine. Isolated cases were reported where the possibility of such an interaction could not be completely excluded, but there was no concrete evidence that such an interaction took place. Concomitant use of terfenadine and macrolide antibiotics has been shown to cause arrhythmia and prolongation of the QT interval. Theophylline has not been shown to interact with azithromycin and theophylline. Triazolam / midazolam There were no significant changes in pharmacokinetic parameters when azithromycin was co-administered with triazolam or midazolam at therapeutic doses. Trimethoprim / sulfamethoxazole Simultaneous administration of trimethoprim/sulfamethoxazole with azithromycin did not significantly affect Cmax, total exposure, or renal excretion of trimethoprim or sulfamethoxazole. The concentration of azithromycin in the blood serum corresponded to those detected in other studies.

How to take, course of administration and dosage

Inside, without chewing, at least 1 hour before or 2 hours after meals,1 time a day. Adults and children over 12 years of age with a body weight of more than 45 kg. For infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues: 500 mg (1 tablet of 500 mg or 2 tablets of 250 mg) 1 time a day for 3 days (a course dose of 1.5 g). For acne vulgaris of moderate severity: 500 mg (1 tablet of 500 mg or 2 tablets of 250 mg) 1 time a day for 3 days, then 500 mg (1 tablet of 500 mg or 2 tablets of 250 mg) 1 time a week for 9 weeks (a course dose of 6.0 g). The first weekly tablet should be taken 7 days after taking the first daily tablet (the 8th day from the start of treatment), the next 8 weekly tablets – at intervals of 7 days. For Lyme disease (initial stage of borreliosis) – erythema migrans: 1 time a day for 5 days: Day 1 – 1.0 g (2 tablets of 500 mg or 4 tablets of 250 mg), then from day 2 to day 5-500 mg (1 tablet of 500 mg or 2 tablets of 250 mg) (course dose 3.0 g).

Overdose

Symptoms: temporary hearing loss, nausea and vomiting, diarrhea. Treatment: symptomatic.

Special instructions

If one dose of Azithromycin is missed, the missed dose should be taken as early as possible, and the subsequent dose should be taken at intervals of 24 hours. Azithromycin should be taken at least 1 hour before or 2 hours after taking antacid medications. Azithromycin should be used with caution in patients with mild to moderate hepatic impairment due to the possibility of developing fulminant hepatitis and severe hepatic insufficiency. In case of impaired liver function: in the presence of symptoms of impaired liver function, such as: rapidly increasing asthenia, jaundice, darkening of the urine, tendency to bleeding, hepatic encephalopathy – therapy with Azithromycin should be discontinued and a study of the functional state of the liver should be conducted.With impaired renal function: No dose adjustment is required in patients with GFR of 10-80 ml / min. As with other antibacterial agents, patients with Azithromycin should be regularly evaluated for the presence of non-susceptible microorganisms and signs of superinfections, including fungal infections. 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 simple dosage regimen. There are no data on a possible interaction between azithromycin and derivatives of ergotamine and dihydroergotamine, but due to the development of ergotism when macrolides are used simultaneously with derivatives of ergotamine and dihydroergotamine, this combination is contraindicated. With prolonged use of Azithromycin, pseudomembranous colitis caused by Clostridium difficile may develop, both in the form of mild diarrhea and severe colitis. If antibiotic-associated diarrhea develops while taking azithromycin, as well as 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded. Drugs that inhibit intestinal motility are contraindicated. Macrolide treatment, including azithromycin, has been associated with prolonged cardiac repolarization and QT interval, which increases the risk of cardiac arrhythmias, including pirouette-type arrhythmias. Caution should be exercised when using azithromycin in patients with proarrhythmogenic factors (especially in elderly patients), including those with congenital or acquired QT prolongation; in patients taking antiarrhythmic drugs of classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotics (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), in patients with impaired water-electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, clinically significant bradycardia, cardiac arrhythmia or severe heart failure. The use of azithromycin can provoke the development of myasthenic syndrome or cause an exacerbation of myasthenia gravis. Influence on the ability to drive vehicles, mechanisms In the development of undesirable effects from the nervous system and the visual organ, care should be taken when performing actions that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

In a dark place at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 2 years. Do not use the drug after the expiration date.

Active ingredient

Azithromycin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Weight

Weight: 130 gr.