Azithromycin pills 500mg, 3pcs

Composition

One film-coated tablet contains: Active ingredient: azithromycin dihydrate ( in terms of azithromycin) – 500,000 mg;

excipients:

microcrystalline cellulose-36,000 mg;

lactose monohydrate-33,464 mg;

povidone K-30-26,000 mg;

crospovidone-26,000 mg;

sodium lauryl sulfate-1,300 mg;

colloidal silicon dioxide-6,600 mg;

magnesium stearate-6,600 mg;

film coating: [hypromellose – 12,000 mg, talc – 4,000 mg, titanium dioxide – 2,200 mg, macrogol 4000 (polyethylene glycol 4000) – 1,800 mg] or [dry mix for film coating containing hypromellose (60%), talc (20%), titanium dioxide (11%), macrogol 4000 (polyethylene glycol 4000) (9%)] – 20,000 mg.

Pharmacological properties

Pharmacotherapeutic group: Antibiotic-utilidad ATKH: 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.

Table 1. Scale of sensitivity of microorganisms to azithromycin (minimum inhibitory concentration (MIC) mg / l):

Micro-organisms	MIC mg / l
Staphylococcus	<1	>2>
Streptococcus A B C G	<025	>05>
S. pneumoniae	<025	>05>
H. influenzae	<012	>4>
M. catarrhalis	<05	>05>
N. gonorrhoeae	<025	>05

In most cases, people are sensitive to azithromycin:

– 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. ;

– 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 that are initially resistant:

– 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:

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 in the blood (04 mg / l) is created after 2-3 hours the apparent volume of distribution – 31 l / kg binding to plasma 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 blood plasma, and in the focus of infection-24-34% higher than in healthy tissues.

Azithromycin has a very long half-life of 30-50 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 (tonsillitis pharyngitis sinusitis otitis media);

– infections of the lower respiratory tract (bronchitis acute exacerbation of chronic bronchitis);

– community-acquired pneumonia including caused by atypical pathogens (see “Special instructions”);

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

– initial stage of Lyme disease (borreliosis) is a migratory erythema (erythema migrans);

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

Use during pregnancy and lactation

Azithromycin is used during pregnancy only when the benefit to the mother outweighs the possible risk to the fetus. During treatment with azithromycin, breastfeeding is suspended.

Contraindications

– hypersensitivity to azithromycin erythromycin other macrolides to catholicam or other components of the drug;

– violation of liver function, severe;

– severe impairment of renal function (creatinine clearance (CC) of less than 40 ml/min);

– children’s age up to 12 years with body weight less than 45 kg (500 mg tablets);

– children’s age up to 3 years (for tablets 125 mg);

– the period of breastfeeding;

– concomitant use with ergotamine and dihydroergotamine;

– lactose intolerance lactase deficiency, glucose-galactose malabsorption.

With caution:

Pregnancy; myasthenia gravis; mild to moderate hepatic impairment; mild to moderate renal impairment (creatinine clearance greater than 40 ml / min); elderly patients; 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 drugs (quinidine procainamide) III (dofetilide amiodarone and sotalol) cisapride terfenadine antipsychotic drugs (pimozide) antidepressants (citalopram) fluoroquinolones (moxifloxacin 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.

Side effects

the incidence 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 01% but less than 1%; rarely – not less than 001% but less than 01%; very rarely – less than 001% (including isolated cases).

Infectious diseases:

infrequently-candidiasis, including oral and genital mucosa;

very rarely-pseudomembranous colitis.

From the side of metabolism and nutrition: often – anorexia.

Allergic reactions:

often-pruritus skin rash;

infrequently-hypersensitivity reactions photosensitization reaction urticaria Stevens-Johnson syndrome angioedema;

very rarely – anaphylactic reaction erythema multiforme toxic epidermal necrolysis.

Blood and lymphatic system disorders:

often – eosinophilia lymphopenia;

infrequently-leukopenia neutropenia;

very rarely – thrombocytopenia hemolytic anemia.

Respiratory system disorders:

infrequently – pneumonia pharyngitis respiratory diseases rhinitis shortness of breath nosebleeds.

Nervous system disorders:

often – headache dizziness paresthesia violation of taste sensations; infrequently-hypesthesia drowsiness insomnia nervousness;

rarely-agitation;

very rarely-anxiety aggression syncope convulsions psychomotor hyperactivity loss of sense of smell (or anosmia) and taste sensations myasthenia gravis anxiety;

frequency unknown – perversion of smell delirium hallucinations.

From the side of the organ of vision: often-a violation of visual clarity.

Hearing disorders and labyrinth disorders:

often-deafness;

infrequently-tinnitus hearing disorder;

rarely-vertigo.

From the cardiovascular system:

infrequently-palpitation sensation “flushes” of blood to the skin of the face;

very rarely-decrease in blood pressure increase in the QT interval arrhythmia of the “pirouette” type ventricular tachycardia.

From the gastrointestinal tract:

very often – nausea flatulence abdominal pain diarrhea;

often-dyspepsia vomiting;

infrequently-constipation gastritis gastroenteritis 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-increased activity of “hepatic” transaminases increased bilirubin concentration hepatitis;

rarely-impaired liver function;

very rarely-cholestatic jaundice liver failure (in rare cases with a fatal outcome, mainly against the background of severe liver dysfunction) liver necrosis fulminant hepatitis.

From the side of the skin:

infrequently – dermatitis dry skin increased sweating.

Musculoskeletal and connective tissue disorders:

often-arthralgia;

infrequently-osteoarthritis myalgia back pain neck pain.

From the genitourinary system:

infrequently-increased plasma urea and creatinine levels dysuria renal pain metrorrhagia testicular dysfunction;

very rarely-interstitial nephritis acute renal failure. Laboratory parameters:

often-a decrease in the concentration of bicarbonates in blood plasma an increase in the amount of: basophils monocytes neutrophils;

infrequently-an increase in the number of platelets an increase in hematocrit; an increase in the activity of alkaline phosphatase an increase in the content of chlorine an increase in the concentration of glucose in blood plasma an increase in the concentration of bicarbonates in blood plasma a change in the content of sodium in blood plasma a change in the concentration of potassium.

Other services:

often-weakness;

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

Interaction

Antacids do not affect the bioavailability of azithromycin but reduce the maximum concentration in the blood by 30%. Therefore, azithromycin should be taken at least one hour before or two hours after taking these drugs or eating.

Azithromycin does not affect the plasma concentrations of carbamazepine cimetidine didanosine efavirenz fluconazole indinavir midazolam triazolam trimethoprim/ sulfamethoxazole cetirizine sildenafil and methylprednisolone when administered concomitantly. 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.

Concomitant use of azithromycin and rifabutin does not affect the concentration of each drug in the blood plasma. 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.

In a pharmacokinetic study involving healthy volunteers who took oral azithromycin (500 mg/day once)for three days and then cyclosporine (10 mg / kg / day once) showed a significant increase in the maximum concentration in blood plasma and the area under the “concentration-time” curve of cyclosporine. 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.

With the simultaneous use of digoxin and azithromycin, it is necessary to monitor the concentration of digoxin in blood plasma. many macrolides increase the absorption of digoxin in the intestine.

If concomitant use with indirect anticoagulants (such as warfarin and other coumarin-type anticoagulants) is necessary, careful monitoring of prothrombin time is recommended.

Concomitant use of terfenadine and macrolide antibiotics has been found to cause arrhythmia and prolongation of the QT interval. Based on this, the above-mentioned complications cannot be excluded with simultaneous use of terfenadine and azithromycin.

Simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times a day) causes an increase in steady-state concentrations of azithromycin in blood plasma. No clinically significant side effects were observed and no dose adjustment is required for azithromycin co-administered with nelfinavir.

Azithromycin weakly interacts with cytochrome P 450 isoenzymes; it was not found that azithromycin participates in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin is not an inducer or inhibitor of cytochrome P450 isoenzymes.

There was no interaction between azithromycin and theophylline.

When used concomitantly with zidovudine, azithromycin does not affect the pharmacokinetic parameters of zidovudine in blood plasma or the elimination of its metabolite glucuronide by night. Nevertheless, the concentration of the active metabolite of phosphorylated zidovudine in peripheral vascular mononuclear cells increases. The clinical significance of this fact is not clear.

Concomitant use of macrolides with ergotamine and dihydroergotamine may cause their toxic effects.

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

How to take, course of use 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 over 45 kg

For infections of the upper and lower respiratory tract ENT organs of the skin and soft tissues: take 1 tablet (500 mg) once a day for 3 days (a course dose of 15 g).

For acne vulgaris of moderate severity: 1 tablet (500 mg) once a day for 3 days, then 1 tablet (500 mg) once a week for 9 weeks (course dose of 60 g). The first weekly tablet should be taken 7 days after taking the first daily tablet (the 8th day from the start of treatment), followed by 8 weekly tablets-at intervals of 7 days.

Lyme disease (initial stage of borreliosis) – erythema migrans: once a day for 5 days: Day 1 – 10 g (2 tablets of 500 mg), then from day 2 to day 5-05 g (1 tablet of 500 mg) (course dose of 30 g).

For urinary tract infections caused by Chlamydiatrachomatis (urethritis cervicitis): uncomplicated urethritis / cervicitis – 10 g (2 tablets of 500 mg) once.

Children aged 3-12 years with a body weight of less than 45 kg

For infections of the upper and lower respiratory tract ENT organs of the skin and soft tissues: based on 10 mg / kg of body weight once a day for 3 days (a course dose of 30 mg / kg). For the convenience of dosing, it is recommended to use table No. 2.

Table 2. Calculation of the dose of Azithromycin for children weighing less than 45 kg:

Body weight	Amount of azithromycin in tablets
18-30 kg	2 tablets of 125 mg (250 mg of azithromycin)
31-44 kg	3 tablets of 125 mg (375 mg of azithromycin)
not less than 45 kg	prescribed doses recommended for adults

For pharyngitis / tonsillitis caused by Streptococcus pyogenes, azithromycin is used at a dose of 20 mg / kg / day for 3 days (a course dose of 60 mg / kg). The maximum daily dose is 500 mg.

Lyme disease (initial stage of borreliosis) – erythema migrans: 20 mg / kg 1 time per day on the 1st day, then at the rate of 10 mg/kg of body weight 1 time per day from the 2nd to the 5th day. The course dose is 60 mg / kg.

Patients with impaired renal function

No dose adjustment is required in patients with mild to moderate renal impairment (creatinine clearance > 40 ml / min).

Patients with impaired liver function

In patients with mild to moderate hepatic impairment, no dose adjustment is required.

Elderly patients

No dose adjustment is required. Since elderly patients may have current proarrhythmogenic conditions, caution should be exercised when using Azithromycin due to the high risk of developing cardiac arrhythmias, including pirouette-type arrhythmias.

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 intervals of 24 hours. Azithromycin should not be used for the treatment of pneumonia in patients who cannot receive oral therapy due to the severity of the disease and/or who have the following risk factors: cystic fibrosis bacteremia or suspected conditions that can change the body’s response to the course of the disease (immunodeficiency functional asplenia, etc. ) patients requiring hospitalization elderly or debilitated patients.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 liver dysfunction such as rapidly increasingsevere asthenia jaundice darkening of the urine tendency to bleed hepatic encephalopathy Azithromycin therapy should be discontinued and a liver function study should be performed.

In patients with mild to moderate renal impairment (creatinine clearance greater than 40 ml/min), Azithromycin therapy should be carried out with caution under the control of renal function. In end-stage renal failure (creatinine clearance less than 10 ml / min), there is an increase in the concentration of azithromycin in blood plasma by 33%.

Microbial resistance may develop if the recommended duration of therapy courses is not observed. 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.

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.

It should be remembered that for the prevention of pharyngitis/tonsillitis caused by Streptococcus pyogenes and for the prevention of acute rheumatic fever, the drug of choice is usually penicillin.

With prolonged use of Azithromycin, pseudomembranous colitis caused by Clostridium Difficile may develop in the form of both mild diarrhea and severe colitis. If diarrhea develops while taking Azithromycin and 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded. The use of drugs that inhibit intestinal motility is contraindicated. Delayed ventricular repolarization syndrome – QT prolongation syndrome-increases the risk of arrhythmias, including pirouette-type arrhythmias, when taking macrolides and azithromycin. Caution when using azithromycin should be observed in patients with prolonged QT interval receiving therapy with class IA III antiarrhythmic drugs cisapride with hypokalemia or hypomagnesemia clinically significant bradycardia arrhythmia or severe heart failure.

Caution should be exercised when concomitantly using Azithromycin and antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin levofloxacin), cyclosporine, as well as in elderly patients.

The use of Azithromycin may 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.

Form of production

Film-coated tablets

Storage conditions

Store in a dark place at a temperature not exceeding 25°C.

Keep out of the reach of children.

Shelf

life is 3 years.

Do not use after the expiration date.

Active ingredient

Azithromycin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets