Azithromycin Avexima pills 500mg, 3pcs

Composition

Active ingredient: azithromycin dihydrate-524.00 mg (based on azithromycin) – 500.00 mg; Excipients (core): calcium hydrophosphate dihydrate 103.60 mg; microcrystalline cellulose 31.20 mg; hyprolose 53.20 mg; sodium lauryl sulfate 2.40 mg;croscarmellose sodium 30.40 mg; magnesium stearate 7.60 mg;talc 7.60 mg; Excipients (film coating):  VIVACOAT®, type PA-1 R-000-20.00 mg (polydextrose-3.0 mg, titanium dioxide-6.0 mg, talc-2.0 mg, polyethylene glycol 3350-1.2 mg, hypromellose 6-7.8 mg).

Pharmacological action

Pharmacotherapeutic group: Antibiotic-Azalid Pharmacodynamics

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 subunit of the ribosome, 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 has activity 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. In most cases, people are sensitive to azithromycin:

• aerobic gram-positive microorganisms:  Staphylococcus aureus
• (methicillin-sensitive), Streptococcus pneumoniae (penicillin-sensitive), Streptococcus pyogenes
• 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.
• other microorganisms:  Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi

Microorganisms capable of developing resistance to azithromycin:

• Streptococcus pneumoniae (penicillin-resistant).

Microorganisms initially resistant to azithromycin:

• aerobic gram-positive microorganisms:  Enterococcus faecalis, Staphylococcus spp. (methicillin-resistant staphylococci with a very high frequency have acquired resistance to macrolides);
• gram-positive bacteria resistant to erythromycin;
• anaerobes:  Bacteroides fragilis.

Pharmacokinetics

Suction.

After oral use, azithromycin is well absorbed and quickly distributed in the body. After a single dose of 500 mg: bioavailability-37% (the effect of “primary passage” through the liver), the maximum concentration (Cmax) (04 mg/l) in blood plasma is reached in 2-3 hours.

Distribution.

Apparent volume of distribution – 311 l / kg binding to plasma proteins is inversely proportional to serum concentration and is 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. It easily passes through histohematic barriers and enters the tissues. The concentration 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 and loses its activity. Output. Azithromycin has a very long half-life of 35-50 hours. The half-life from tissues is much 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 intestine and 6% through the kidneys.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to azithromycin:

• upper respiratory tract and ENT infections (sinusitis, tonsillitis, pharyngitis, otitis media)
• lower respiratory tract infections (acute bronchitis, exacerbation of chronic bronchitis, pneumonia, including those caused by atypical pathogens)
• skin and soft tissue infections (erysipelas, impetigo, secondary infected dermatoses, acne vulgaris of moderate severity)
• urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis)
• the initial stage of Lyme disease (borreliosis) is erythema migrans

Use during pregnancy and lactation

Pregnancy

During pregnancy, azithromycin is used only if the intended benefit to the mother exceeds the potential risk to the fetus. Breast-feedingif you need to use the drug during breastfeeding, it is recommended to stop breastfeeding.

Contraindications

• Hypersensitivity to azithromycin, erythromycin, other macrolides or ketolides, or other components of the drug
• severe hepatic insufficiency (Child-Pugh class C)
• children under 12 years of age with a body weight of less than 45 kg (for 500 mg tablets)
• children under 3 years of age (for 125 mg tablets)
• concomitant use with ergotamine and dihydroergotamine
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption

With caution

• , myasthenia gravis;
• mild to moderate hepatic impairment (Child-Pugh class A and B);
• end-stage renal failure with a glomerular filtration rate (GFR) of less than 10 ml / min;
• in patients with proarrhythmogenic factors (especially in elderly patients): with congenital or acquired QT prolongation in patients receiving therapy with antiarrhythmic drugs class IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotics (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin, levofloxacin), disorders of water and electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, clinically significant bradycardia, arrhythmia or severe heart failure;
• the simultaneous use of digoxin, warfarin, cyclosporine.

Side effects

Infectious diseases: infrequently-candidiasis (including oral and genital mucosa), pneumonia, pharyngitis, gastroenteritis, respiratory diseases, rhinitis; unknown frequency-pseudomembranous colitis.

From the blood and lymphatic system: infrequently-leukopenia, neutropenia, eosinophilia; very rarely-thrombocytopenia, hemolytic anemia. From the side of metabolism:  infrequently – anorexia. Allergic reactions: infrequently-angioedema, hypersensitivity reaction; unknown frequency – anaphylactic reaction. From the nervous system: often-headache; infrequently-dizziness, impaired taste sensations, 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 visual organ:  infrequently-visual impairment. Hearing disorders and labyrinth disorders: infrequently-hearing disorder, vertigo; unknown frequency-hearing impairment up to deafness and / or tinnitus. From the cardiovascular system: infrequently-palpitations, flushes of blood to the face; unknown frequency-decrease in blood pressure, increase in the QT interval on the ECG, arrhythmia of the “pirouette” type, ventricular tachycardia. From the respiratory system: infrequently-shortness of breath, nosebleeds. From the digestive system: 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. From the liver and biliary tract: infrequently-hepatitis; rarely-impaired liver function, 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. From the skin and subcutaneous tissues: infrequently-skin rash, pruritus, urticaria, dermatitis, dry skin, sweating; rarely-photosensitization reaction; unknown frequency-Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme. Musculoskeletal disorders: 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. Local reactions: often-pain and inflammation at the injection site. Other services:  infrequently-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 AST, ALT, 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 blood glucose, an increase in the number of platelets, an increase in hematocrit, an increase in the concentration of bicarbonates in blood plasma, a change in the content of sodium in blood plasma.

Interaction

Antacid medications

Antacids do not affect the bioavailability of azithromycin but reduce the Cmax in blood plasma by 30%. Therefore, azithromycin should be taken at least 1 hour before or 2 hours after taking antacids and food.

Cetirizine

Concomitant 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 QT interval.

Didanosine (dideoxyinosine)

Concomitant use of azithromycin (1200 mg / day) and didanosine (400 mg / day) There were no changes in the pharmacokinetic parameters of didanosine in 6 HIV-infected patients 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 P-glycoprotein substrate in the blood serum. Thus, when using azithromycin and digoxin simultaneously, it is necessary to take into account the possibility of increasing the concentration of digoxin in the blood serum.

Zidovudine

Concomitant use 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.

Ergot alkaloids

Given the theoretical possibility of ergotism, concomitant use of azithromycin with ergot alkaloid derivatives is not recommended.

Drugs that are metabolized with the participation of cytochrome P450 isoenzymes Azithromycin weakly interacts with cytochrome P450 isoenzymes. Azithromycin was not found to be involved in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin is not an inhibitor or inducer of cytochrome P450 isoenzymes.

Pharmacokinetic studies were conducted on the concomitant use of azithromycin and drugs that are metabolized with the participation of cytochrome P450 isoenzymes.

Atorvastatin

Concomitant use of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause changes in blood concentrations of atorvastatin (based on the analysis of HMG-CoA reductase inhibition). However, in the post-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 plasma concentrations of carbamazepine and its active metabolite in patients receiving concomitant azithromycin.

Cimetidine

In pharmacokinetic studies of the effect of a single dose of cimetidine on the pharmacokinetics of azithromycin, no changes in the pharmacokinetics of azithromycin were detected when cimetidine was administered 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 use 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 indirect oral anticoagulants (coumarin derivatives).

Cyclosporine

In a pharmacokinetic study involving healthy volunteers who took oral azithromycin (500 mg/day once)for 3 days and then cyclosporine (10 mg / kg / day once), a significant increase in Cmax and the area under the concentration-time curve from 0 to 5 hours (AUC0-5) of cyclosporine in blood plasma was detected. Caution should be exercised when using these drugs simultaneously. If the concomitant use of these drugs is necessary, it is necessary to monitor the concentration of cyclosporine in the blood plasma and adjust the dose accordingly.

Efavirenz

Concomitant 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

Concomitant use 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 a decrease in the Cmax of azithromycin (by 18%) in blood plasma was observed, which was not clinically significant.

Indinavir

Concomitant use of azithromycin (1200 mg once) did not cause a statistically significant effect on the pharmacokinetics of indinavir (800 mg 3 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 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, no causal relationship has been established between the use of azithromycin and rifabutin and neutropenia.

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 or its main circulating metabolite in blood plasma.

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 macrolides has been shown to cause arrhythmia and prolongation of the QT interval.

Theophylline

There was no interaction between 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

Concomitant use of trimethoprim / sulfamethoxazole with azithromycin did not significantly affect the total plasma exposure or renal excretion of trimethoprim or sulfamethoxazole. Serum concentrations of azithromycin were consistent with detectable concentrations in other studies.

How to take it, course of use and dosage

The drug is taken orally 1 time/day for 1 hour before or 2 hours after meals, without chewing.

Adults and children over 12 years of age and weighing more than 45 kg with infections of the upper and lower respiratory tract, ENT organs, skin and soft tissue infections ( with the exception of chronic migrating erythema) – 500 mg / day for 1 dose for 3 days (course dose-1.5 g). For acne vulgaris of moderate severity-500 mg 1 time/day for 3 days, then 500 mg 1 time per week for 9 weeks; the course dose is 6 g. The first weekly dose should be taken 7 days after the first daily dose (the 8th day from the start of treatment), the next 8 weekly doses – with an interval of 7 days. For acute infections of the genitourinary organs (uncomplicated urethritis or cervicitis) – 1 g once. For Lyme disease (borreliosis) for the treatment of stage I (erythema migrans) – 1 g on day 1 and from day 2 to day 5-500 mg daily (course dose-3 g). For the treatment of elderly patients over 65 years of age, the same doses are used as for adults. Since this category of patients may have proarrhythmogenic factors, it is necessary to pay special attention to the possibility of developing arrhythmia and ventricular tachycardia of the “pirouette”type. If renal function is impaired (creatinine clearance greater than 40 ml/min), no dose adjustment is required.No dose adjustment is required for moderate hepatic impairment.

Overdose

Symptoms: Nausea, temporary hearing loss, 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 24 – hour intervals.

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 the presence of symptoms of impaired liver function such as rapidly increasing asthenia jaundice darkening of the urine tendency to bleeding hepatic encephalopathy azithromycin therapy should be discontinued and a study of the functional state of the liver should be conducted.

With impaired renal function: in patients with GFR of 10-80 ml/min, no dose adjustment is required, azithromycin therapy should be carried out with caution under the control of renal function.

As with other antibacterial agents, patients with azithromycin should be regularly examined for the presence of non-susceptible microorganisms and signs of superinfections, including fungal ones. Azithromycin should not be used for longer courses than indicated in the instructions, since the pharmacological properties of azithromycin allow us to recommend a short and simple dosage regimen.

There are no data on possible interactions between azithromycin and ergotamine and dihydroergotamine derivatives, but due to the development of ergotism when macrolides are co-administered with ergotamine and dihydroergotamine derivatives, this combination is not recommended.

With prolonged use of azithromycin, pseudomembranous colitis caused by Clostridium difficile may develop both in the form of mild diarrhea and severe colitis.

Clostridial pseudomembranous colitis should be excluded if antibiotic-associated diarrhea develops while taking azithromycin and 2 months after the end of therapy. Drugs that inhibit intestinal motility are contraindicated.

When treated with macrolides, including azithromycin, prolongation of cardiac repolarization and QT interval was observed, which increases the risk of developing 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 Class IA antiarrhythmic drugs (quinidine procainamide) III (dofetilide amiodarone and sotalol) cisapride terfenadine antipsychotic drugs (pimozide) antidepressants (citalopram) fluoroquinolones (moxifloxacin and levofloxacin) in patients with impaired 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 can provoke the development of myasthenic syndrome or cause an exacerbation of myasthenia gravis.

Influence on the ability to drive vehicles and mechanisms:

With 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.

Active ingredient

Azithromycin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets