Azithromycin Zentiva - instructions for use, dose, side effects, contraindications

core: starch corn pregelatinized corn - 42,500 mg, croscarmellose sodium - 9,000 mg, calcium hydrophosphate - 115,625 mg, magnesium stearate - 6,375 mg, sodium lauryl sulfate - 1,500 mg.

shell: hypromellose 2910/5 - 7,300 mg, titanium dioxide - 3,100 mg, macrogol 6000 - 0,700 mg, talc - 1,250 mg, emulsion simethicone SE 4 (water - 67.4%, siloxanes and silicones - 30.0%, methylated cellulose - 2.5%, sorbic acid - 0.1%) - 0.050 mg, polysorbate 80 - 0.100 mg.

Each tablet, film-coated 500 mg contains:

active substance:

azithromycin 500,000 mg (in the form of azithromycin dihydrate - 524.052 mg); Excipients:

core: starch corn pregelatinized - 85,000 mg, croscarmellose sodium - 18,000 mg, calcium hydrophosphate - 231.250 mg, magnesium stearate - 12.750 mg, sodium lauryl sulfate - 3,000 mg.

shell: hypromellose 2910/5 - 14,600 mg, titanium dioxide - 6,200 mg, macrogol 6000 - 1,400 mg, talc - 2,500 mg, emulsion simethicone SE 4 (water - 67.4%, siloxanes and silicones - 30.0%, methylated cellulose - 2.5%, sorbic acid - 0.1%) - 0.100 mg, polysorbate 80 - 0.200 mg.

Description:

250 mg tablets: round, biconvex tablets, covered with a film shell, from white to almost white.

Tablets 500 mg: tablets of oblong form, film-coated, from white to almost white.

Pharmacotherapeutic group:Antibiotic - azalide

ATX: & nbsp

J.01.F.A.10 Azithromycin

Pharmacodynamics:

Azithromycin is a bacteriostatic broad-spectrum 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 protein synthesis of a microbial cell. Communicating with 50S-a subunit of the ribosome, inhibits peptidranslokase at the stage of translation, inhibits protein synthesis, slowing the growth and multiplication 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.

Gram-positive cocci are sensitive to azithromycin: Streptococcus pneumoniae (penicillin-sensitive strains),Streptococcus pyogenes, Staphylococcus aureus (methicillin-sensitive strains); aerobic gram-negative bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis, Pasteurella multocida, Neisseria gonorrhoeae; some anaerobic microorganisms: Clostridium perfringens, Fusobacterium spp., Prevotella spp., Porphyriomonas spp .; and also: Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.

Microorganisms with acquired resistance to azithromycin: aerobic Gram-positive microorganisms - Streptococcus pneumoniae (penicillin-resistant strains and strains with moderate sensitivity to penicillin). Microorganisms with natural resistance: aerobic gram-positive microorganisms - Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis (methicillin-resistant strains), anaerobic microorganisms - Bacteroides fragilis.

Cases of cross-resistance between Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococcus), Enterococcus faecalis and Staphylococcus aureus (methicillin-resistant strains) to erythromycin, azithromycin, other macrolides and lincosamides are described.

Azithromycin has not been used to treat infectious diseases caused by Salmonella typhi (MIC <16 mg / L) and Shigella spp.

The sensitivity scale of microorganisms to azithromycin (Minimum inhibitory concentration (MIC) mg / l).

Microorganisms	MIC, mg / l
Microorganisms	Sensitive	Sustainable
Staphylococcus spp.	< 1	>2
Streptococcus spp. (groups A, B, C, G)	<0,25	>0,5
Streptococcus pneumoniae	<0,25	>0,5
Haemophilus influenzae	<0,12	>4
Moraxella catarrhalis	<0,25	>0,5
Neisseria gonorrhoeae	<0,25	>0,5

Pharmacokinetics:

After oral administration azithromycin well absorbed from the gastrointestinal tract, which is due to its stability in acidic environment and lipophilicity, and quickly distributed in the body. After a single oral administration of 500 mg of azithromycin, the maximum concentration in the blood plasma is reached after 2-3 hours and is 0.4 mg / l. Bioavailability is 37%. Azithromycin well penetrates the respiratory tract, organs and tissues of the urogenital tract (in particular, the prostate gland), the skin and soft tissues. High concentration in tissues (10-50 times higher than in plasma) and a long half-life are due to low binding of azithromycin to blood plasma proteins, as well as its ability to penetrate into eukaryotic cells and concentrate in medium with a low pH surrounding the lysosome. This, in turn, determines the large apparent volume of distribution (31.1 l / kg) and high plasma clearance. The ability of azithromycin to accumulate mainly in lysosomes is especially important for the eradication of intracellular pathogens. It is proved that phagocytes deliver azithromycin in places of infection localization, where it is released during phagocytosis. The concentration of azithromycin in the foci of infection is significantly higher than in healthy tissues (an average of 24-34%). Despite the high concentration in phagocytes, azithromycin does not have a significant effect on their function. The connection with plasma proteins is 7-50% (inversely proportional to the concentration in the blood).

In the liver azithromycin demethylated; the metabolites formed are not active.

In azithromycin, prolonged T_1/2- 35-50 h. The therapeutic concentration of azithromycin is maintained up to 5-7 days after the last dose, which allowed to develop short (3-day and 5-day) courses of treatment. Azithromycin is output mainly in the unmodified form: 50% through the intestine, 6% through the kidneys.

Indications:

Infectious-inflammatory diseases caused by microorganisms susceptible to azithromycin:

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

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

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

Uncomplicated urinary tract infections caused by Chlamydia trachomatis (urethritis and / or cervicitis);

The initial stage of Lyme disease (borreliosis) is migratory erythema (erythema migrans).

Contraindications:

- Hypersensitivity to azithromycin, erythromycin, other macrolides, or ketolides, or other components of the drug;

- Dysfunction of the liver of a severe degree;

- Violation of the function of the kidneys of severe degree (creatinine clearance <40 ml / min);

- Children under 12 years old with body weight less than 45 kg;

- The period of breastfeeding;

- Simultaneous reception with ergotamine and dihydroergotamine.

Carefully:

Myasthenia gravis; violations of liver function of mild and moderate severity; disturbance of renal function of mild and moderate severity (creatinine clearance> 40 ml / min); at arrhythmias, the presence of pro-arrhythmic factors in patients with prolonged QT interval (congenital and acquired) or risk factors for QT prolongation (receiving antiarrhythmic drugs of classes IA, III, cisapride, hypokalemia or hypomagnesemia, clinically significant bradycardia or severe heart failure); simultaneous use of antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin, levofloxacin), cyclosporine, terfenadine, warfarin, digoxin; elderly patients.

Pregnancy and lactation:

In pregnancy, taking the drug is only possible if the intended benefit to the mother exceeds the potential risk to the fetus.

At the time of treatment with azithromycin, breastfeeding is suspended.

Dosing and Administration:

Inside, 1 hour before or 2 hours after eating, without chewing, 1 time per day.

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, with infections of the skin and soft tissues (excluding chronic migrating erythema) - 500 mg / day for 1 reception for 3 days (exchange dose - 1.5 g); - with acne vulgaris of medium severity: 1 tab. (500 mg) once a day for 3 days, then 1 table. (500 mg) once a week for 9 weeks; the course dose is 6 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 subsequent 8 weekly tablets - with an interval of 7 days; - with acute infections of the urogenital organs (uncomplicated urethritis or cervicitis) - 1 g (2 tablets, 500 mg) once;

- with Lyme disease (borreliosis) for the treatment of stage I (erythema migrans) - 1 g on the first day and from 2 to 5 days 500 mg daily (course dose - 3 g);

Patients of advanced age (age over 65 years)

For the treatment of elderly patients, the same dosages are used as for adults. Taking into account that among elderly patients there may be people with the presence of arrhythmogenic factors, it is necessary to pay special attention to the possibility of developing cardiac arrhythmia and pirouette ventricular tachycardia in them.

If the kidney function is impaired (creatinine clearance is more than 40 ml / min) - dose adjustment is not required.

If there is a violation of the liver: with a moderate violation of liver function, dose adjustment is not required.

Side effects:

The incidence of adverse reactions is represented by organ systems and according to the classification of the Medical Dictionary of Regulatory Activities (MedDRA): very frequent (> 10%), frequent (≥ 1% and <10%), infrequent (≥ 0.1% and <1%), rare (≥ 0.01% and <0.1%), very rare (<0.01%), the frequency is unknown (it is not possible to determine the frequency of occurrence according to available data).

Violations from the blood and lymphatic system: frequent - eosinophilia, lymphocytopenia; infrequent - leukopenia, neutropenia; rare thrombocytopenia, hemolytic anemia.

Violations from the nervous system: frequent - headache, dizziness, paresthesia, a violation of taste; infrequent - hypoesthesia, drowsiness, insomnia; very rare - anxiety, fainting, convulsions, psychomotor hyperactivity, loss of smell (or anosmia), perversion of smell, loss of taste sensations, myasthenia gravis.

Disorders of the psyche: infrequent - increased excitability, insomnia; rare - agitation; frequency unknown - aggressiveness, anxiety, delirium, hallucinations.

Disorders from the side of the organ of vision: frequent - impaired vision.

Hearing disorders and labyrinthine disorders: frequent - reversible hearing impairment up to deafness (with long-term administration of high doses); infrequent - noise in the ears; rare - vertigo.

Disorders from the heart: infrequent - a feeling of palpitations; very rare - lengthening of the interval Q-T, arrhythmia of the type "pirouette", ventricular tachycardia.

Violations from the vessels: infrequent - "tides" of blood to the face; frequency unknown - lowering blood pressure.

Disorders from the gastrointestinal tract: very frequent - nausea, flatulence, diarrhea; frequent - pain in the abdomen, vomiting,dyspepsia; infrequent - constipation, gastritis, dysphagia, bloating, dryness of the oral mucosa, belching, ulcers of the oral mucosa, increased secretion of the salivary glands; very rare - change the color of the tongue.

Disorders from the endocrine system: very rare - pancreatitis.

Disorders from the kidneys and urinary tract: infrequent - increased concentration of urea and creatinine in the blood plasma, dysuria, pain in the kidneys; very rare -interstitial nephritis, acute renal failure.

Violations from the genitals and breast: infrequent - metrorrhagia, dysfunction of the testicles.

Disorders from the immune system: infrequent - hypersensitivity reactions, angioedema; frequency unknown - anaphylactic reaction.

Disturbances from the skin and subcutaneous tissues: frequent - itchy skin, skin rash; infrequent - photosensitization reaction, hives, Stevens-Johnson syndrome, dry skin, sweating; very rare - erythema multiforme, toxic epidermal necrolysis.

Disorders from the metabolism and nutrition: frequent - anorexia, a change in the concentration of potassium.

Infectious diseases: infrequent - candidiasis, incl. mucous membrane of the oral cavity and genitals, vaginal infections, pneumonia, fungal infections, bacterial infections, pharyngitis, gastroenteritis, respiratory diseases, rhinitis; frequency unknown - pseudomembranous colitis.

Disorders from the liver and bile ducts: infrequent - hepatitis; rare - a violation of liver function; very rare - cholestatic jaundice, liver failure (in rare cases with a fatal outcome, mainly on the background of severe violations of the liver function); liver necrosis, fulminant hepatitis.

Disturbances from the musculoskeletal system and connective tissue: infrequent - osteoarthritis, myalgia, back pain, neck pain; frequency unknown - arthralgia.

Disturbances from the respiratory system, chest and mediastinal organs: infrequent - epistaxis, dyspnea.

General disorders and disorders at the site of administration: frequent - weakness; infrequent - chest pain, peripheral edema, asthenia, malaise, face swelling, fever

Laboratory and instrumental data: frequent - an increase in the number of basophils, monocytes, neutrophils,decrease or increase in the concentration of bicarbonates in the blood plasma; infrequent - increasing the activity of "liver" transaminases, increasing the concentration of bilirubin in the blood plasma, increasing the activity of alkaline phosphatase, increasing the level of chlorine in the blood plasma, increasing the concentration of glucose in the blood plasma, increasing the number of platelets, increasing hematocrit, changing the sodium content in blood plasma.

Overdose:

Symptoms: nausea, temporary loss of hearing, vomiting, diarrhea, abdominal pain, impaired liver function.

Treatment: gastric lavage, symptomatic therapy (reception of activated charcoal), control of vital functions.

Interaction:

Antacid agents (aluminum and magnesium-containing) slow down and reduce the absorption of azithromycin (for oral forms), so the interval between their intake should be 1 hour before or 2 hours after ingestion and these medications.

When combined azithromycin does not affect the concentration of atorvastatin in the blood plasma, but there is a risk of rhabdomyolysis.

When the combined use of warfarin and azithromycin (in normal doses), the changes in prothrombin time are notHowever, given that the interaction of macrolides and warfarin may enhance the anticoagulation effect, patients need to carefully monitor prothrombin time.

With the joint administration of digoxin and azithromycin, it is necessary to control the concentration of digoxin in the blood, since many macrolides increase the absorption of digoxin in the intestine, thereby increasing its concentration in the blood plasma.

If combined with cimetidine 2 hours before taking azithromycin, there is no effect on the pharmacokinetics of azithromycin.

When joint use of azithromycin with rifabutin should take into account the risk of developing neutropenia.

There is no evidence of the effect of azithromycin on blood concentrations of triazolam, midazolam, efavirenz, fluconazole, indinavir, trimethoprim / sulfamethoxazole, when combined, but this interaction should not be ruled out, since the interaction of macrolides with the above drugs is known.

With the joint use of azithromycin with ergotamine or dihydroergotamine, their toxic effect (vasospasm, dysesthesia) may be increased.There is no data on the possible interaction between azithromycin and derivatives of ergotamine and dihydroergotamine, but because of the development of ergotism with the simultaneous use of macrolides with derivatives of ergotamine and dihydroergotamine, these combinations are contraindicated.

Caution should be exercised when using terfenadine and azithromycin concomitantly, since it has been established that simultaneous administration of terfenadine and various types of antibiotics causes arrhythmia and lengthening of the Q-T interval. Proceeding from this, it is impossible to exclude the aforementioned complications in the joint use of terfenadine and azithromycin.

If it is necessary to simultaneously use with cyclosporine, it is recommended to monitor the concentration of cyclosporin in the blood plasma.

Simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times a day) causes an increase in the equilibrium concentration of azithromycin in the blood plasma. Clinically significant side effects were not observed and correction of the dose of azithromycin with its simultaneous application with nelfinavir is not required.

When combined with zidovudine azithromycin does not affect the pharmacokinetic parameters of zidovudine in blood plasma or the excretion of his and his metabolite glucuronide by the kidneys, but at the same time the concentration of the active metabolite - phosphorylated zidovudine - in mononuclear cells of peripheral vessels increases. The clinical significance of this fact is unclear.

Azithromycin weakly interacts with isoenzymes of the cytochrome P450 system. It was not revealed that azithromycin participates in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin It is not an inducer and inhibitor of isoenzymes to the cytochrome P450 system.

When combined azithromycin does not affect the concentration in the blood plasma of drugs: carbamazepine, cimetidine, didanosine, efavirenz, fluconazole, indinavir, midazolam, theophylline, triazolam, cetirizine, trimethoprim / sulfamethoxazole, sildenafil, rifabutin and methylprednisolone.

Special instructions:

If you miss one dose of Azithromycin Zentiva, the missed dose should be taken as soon as possible, and the subsequent dose - with interruptions of 24 hours.

The drug Azithromycin Zentiva should be used at least 1 hour before and 2 hours after taking antacid preparations.

After the withdrawal of the treatment, hypersensitivity reactions in some patients may persist, which requires specific therapy under the supervision of a physician.

The drug Azithromycin Zentiva should be used with caution in patients with mild to moderate liver function impairment due to the possibility of developing fulminant hepatitis and severe hepatic insufficiency. In the presence of symptoms of liver dysfunction, such as rapidly increasing asthenia, jaundice, darkening of the urine, a tendency to bleeding, hepatic encephalopathy, the drug should be discontinued and an examination of the functional state of the liver should be performed.

For mild to moderate renal impairment (creatinine clearance> 40 mL / min), Azithromycin Zentiva should be administered with caution under the control of the kidney function. At the terminal stage of renal failure (creatinine clearance <10 ml / min), the concentration of azithromycin in the blood plasma is increased by 33%.

Azithromycin is not a drug of choice for the prevention of pharyngitis / tonsillitis caused by Streptococcus pyogenes, and the prevention of acute rheumatic fever.

As with the use of other antibacterial drugs, with the drug Azithromycin Zentiva should regularly monitor patients for the presence of resistant microorganisms and signs of development of superinfections, including. fungal.

The drug Azithromycin Zentiva should not be used for longer courses than indicated in the instructions, because pharmacokinetic properties of azithromycin allow us to recommend a short and convenient dosage regimen.

With prolonged use of Azithromycin Zentiva, the development of pseudomembranous colitis caused by Clostridium difficile, both in the form of mild diarrhea and in the form of severe colitis, is possible. With the development of diarrhea against the background of taking azithromycin, and also 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded.

The syndrome of delayed repolarization of the ventricles (syndrome of prolongation of the interval QT) increases the risk of arrhythmias (including arrhythmias such as "pirouette") against the background of taking macrolides.Caution when using azithromycin should be observed in patients with prolonged QT interval receiving therapy with antiarrhythmic agents of classes IA, III, cisapride, hypokalemia or hypomagnesemia, clinically significant bradycardia, arrhythmia or severe heart failure.

The use of macrolides may provoke the development of myasthenic syndrome or cause an exacerbation of myasthenia gravis.

Effect on the ability to drive transp. cf. and fur:

With the development of undesirable effects from the nervous system and the organ of vision, care should be taken when performing actions requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Tablets, film-coated 250 mg, 500 mg.

Packaging:Tablets, film-coated 250 mg: 3 or 6 tablets in a blister of PVC / A1. For 1 or 2 blisters (3 tablets each) or 1 blister (6 tablets) together with the instructions for use are placed in a cardboard box.
Tablets, film-coated 500 mg: 3 tablets in a blister of PVC / A1. Each blister along with the instruction for use is placed in a cardboard box.

Storage conditions:

Does not require special storage conditions.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-002491

Date of registration:30.12.2011

Date of cancellation:2017-12-19

The owner of the registration certificate:Zentiva c.s.Zentiva c.s. Czech Republic

Manufacturer: & nbsp

ZENTIVA, k.s. Czech Republic

Representation: & nbspZENTIVA PHARMA, LLCZENTIVA PHARMA, LLC

Information update date: & nbsp19.12.2017

Illustrated instructions

Instructions

Azithromycin Zentiva (Azithromycin Zentiva)