Azithromycin pills 500mg, 3pcs – Borisov

Composition

One tablet contains:

Active ingredient:

azithromycin-500 mg (in the form of azithromycin dihydrate-524.05 mg);

excipients:  calcium hydrophosphate dihydrate, hypromellose, corn starch, starch 1500, partially pregelatinized corn starch, sodium lauryl sulfate, magnesium stearate, microcrystalline cellulose, Opadray II (including polyvinyl alcohol, talc, macrogol 3350, lecithin (soy), titanium dioxide E 171, iron oxide yellow E 172, aluminum varnish based on indigo carm and on E 132).

Pharmacological action

Pharmacotherapy group

Antibiotic-azalide

ATX code

J01FA10

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 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.

Scale of sensitivity of microorganisms to azithromycin (Minimum inhibitory concentration (MIC) mt / l):

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 perffingens

Fusobacterium spp.

Prevotella spp.

Porphyriomonas spp.

4. Other microorganisms

Chlamydia trachomatis

Chlamydia pneumoniae

Chlamydia psittaci

Mycoplasma pneumoniae

Mycoplasma hominis

Borrelia burgdorferi

Microorganisms capable of developing resistance to azithromycin

Gram-positive aerobes

Streptococcus pneumoniae penicillin-resistant

Initially resistant microorganisms

Gram-positive aerobes

Enterococcus faecalis

Staphylococci (methicillin-resistant staphylococci with a very high frequency have acquired resistance to macrolides).

Gram-positive bacteria resistant to erythromycin.

Anaerobes

Baderoides fragilis

Pharmacokinetics:

After oral use, azithromycin is well absorbed and quickly distributed in the body. After a single dose of 500 mg bioavailability – 37% (“first pass” effect) the maximum concentration (04 mg/l) in the blood is created after 2-3 hours the apparent volume of distribution – 311 l / kg binding to proteins is inversely proportional to the concentration in the blood 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 plasma, and in the focus of infection-24-34% higher than in healthy tissues.

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% by the intestines and 6% by the kidneys. In the liver, it is demethylated losing its activity.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to azithromycin:

– infections of the upper respiratory tract and ENT organs (sinusitis tonsillitis pharyngitis otitis media);

– infections of the lower respiratory tract (bronchitis acute exacerbation of chronic bronchitis and pneumonia, including those caused by atypical pathogens);

infections of skin and soft tissues (erysipelas impetigo secondarily infected dermatoses, acne vulgaris moderate severity);

– urinary tract infection caused by Chlamydia trachomatis (urethritis cervicitis);

– Lyme disease (borreliosis) in the initial stage (erythema migrans).

Use during pregnancy and lactation

The use of the drug during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.

If it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Contraindications

-Hypersensitivity to azithromycin and other components of the drug to erythromycin and other macrolides ketolides to soy and peanuts;

– severe liver failure (Child-Pugh class C);

– children under 12 years of age with a body weight of less than 45 kg;

– simultaneous use with ergotamine and dihydroergotamine.

With caution:

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

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 less than 10%; infrequently – not less than 01% but less than 1%; rarely – not less than 001% but less than 01%; very rarely – less than 001%; frequency unknown – cannot be estimated from 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-synesthesia anxiety aggression syncope 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-vertigo hearing disorder; unknown frequency – hearing disorders including deafness and / or tinnitus.

From the cardiovascular system:  infrequently-palpitation sensation “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) acute generalized exanthematous pustulosis (OGEP)

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: infrequently-edema asthenia malaise feeling tired facial edema chest pain fever peripheral edema.

Laboratory data: often – decrease in the number of lymphocytes increase in the number of eosinophils increase in the number of basophils increase in the number of monocytes increase in the number of neutrophils decrease in the concentration of bicarbonates in the blood plasma; infrequently – increase in the activity of aspartate aminotransferase alanine aminotransferase increase in the concentration of bilirubin in the blood plasma increase in the concentration of urea in the blood plasma increase in the concentration of creatinine in the blood plasma change in the content of potassium in the blood plasma increase in the activity of alkaline phosphatase in the blood plasma increase in the content of chlorides in the blood blood glucose concentrations increase in platelet count decrease in hematocrit increase in bicarbonate concentration in blood plasma change in sodium content in blood plasma.

Interaction

Antacid medications

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 one hour before or two hours after taking these drugs and eating.

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) in 6 HIV-infected patients showed 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 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.

Azithromycin weakly interacts with cytochrome P450 isoenzymes. It was not found that azithromycin is involved in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin is not an inhibitor or inducer of cytochrome P450 isoenzymes.

Ergot alkaloids

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

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 the concentration of atorvastatin in blood plasma (based on the analysis of inhibition of MMC-CoA reductase). 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 oral indirect 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 the maximum concentration in blood plasma (Cmax) and the area under the concentration-time curve (AUC0-5) of cyclosporine 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%)was observed which was not clinically relevant.

Indinavir

Concomitant 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 3 times a day) causes an increase in steady-state concentrations 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.

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

The concomitant use of trimethoprim / sulfamethoxazole with azithromycin did not significantly affect the Cmax of total exposure or renal excretion of trimethoprim or sulfamethoxazole. Serum concentrations of azithromycin were consistent with those found in other studies.

How to take it, course of use and dosage

Inside 1 hour before or 2 hours after meals 1 time a day without chewing with a sufficient amount of water.

Adults and children over 12 years of age with a body weight of more than 45 kg:

– for upper respiratory tract and ENT infections (sinusitis, tonsillitis, pharyngitis, otitis media) – 500 mg / day in one dose for 3 days (course dose-15 g);

– for acne vulgaris of moderate severity-500 mg / day for 3 days, then 500 mg / day 1 time a week for 9 weeks (course dose-60 g). The first weekly the tablet should be applied after 7 days after the first daily tablets (8th day of treatment) next 8 weekly