AzitRus - instructions for use, doses, side effects, contraindications

Azithromycin is a bacteriostatic broad-spectrum antibiotic from the group of macrolides-azalides. We have a wide spectrum of antimicrobial action. The mechanism of the action of azithromycin is associated with the suppression of the synthesis of the protein of the microbial cell. By binding to the 508 subunit of the ribosome, it inhibits peptidranslokase at the translation stage and suppresses protein synthesis, and bacterial growth AT high concentrations have bactericidal effect.

It has activity against a number of gram-positive, gram-negative, anaerobes, intracellular and other microorganisms.

Microorganisms may initially be resistant to the action of the antibiotic or may acquire resistance to it.

Sensitive microorganisms:

aerobic gram-positive microorganisms - Staphylococcus aureus (methicillin-sensitive strains), Streptococcus pneumoniae (penicillin-sensitive strains), 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 .. Porphiyriomonas spp .;

other microorganisms - Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci. Mycoplasma pneumoniae. Mycoplasma hominis, Borrelia burgdorferi;

Microorganisms that can develop resistance to azithromycin:

aerobic gram-positive microorganisms - Streptococcus pneumoniae (penicillin-resistant strains and strains with an average sensitivity to penicillin).

Microorganisms with initial resistance:

aerobic gram-positive microorganisms - Enterococcus faecalis. Staphylococci (methicillin-resistant strains),

anaerobic makeup positive microorganisms - Bacteroides fragilis.

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

Microorganisms	MITO mg / l *
Microorganisms	Sensitive	Sustainable
Staphylococcus	no more 1	more than 2
Streptococcus A. B, C, G	not more than 0,25	more than 0.5
Streptococcus pneumoniae	not more than 0,25	more than 0.5
Haemophilus influenzae	not more than 0.12	more than 4
Moraxella catarrhal is	no more than 0.5	more than 0.5
Neisseria gonorrhoeae	not more than 0,25	more than 0.5

Pharmacokinetics:

Azithromycin is rapidly absorbed from the gastrointestinal tract, which is due to its stability in the acidic environment and lipophilicity. Quickly distributed throughout the body, while in the tissues are reached high concentrations of antibiotic. After oral administration of 500 mg, the maximum concentration of azithromycin in the blood plasma is achieved after 2.5-2.9 hours and is 0.4 mg / l. Bioavailability is 47.5% Azithromycin well penetrates the respiratory tract, organs and tissues of the urogenital tract (in particular, the prostate gland), the skin and soft tissues. ATHigh concentrations 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 eukaryotic cells and concentrate in a medium with a low pH. surrounding the lysosome. This, in turn, determines a 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 elimination 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%) and correlates with the degree of inflammatory edema. Azithromycin remains in bactericidal concentrations for 5-7 days after the last dose, which allowed the development of short (3-day and 5-day) treatment courses.

In the liver demethylated, the metabolites formed are not active.

Excretion of azithromycin from the blood plasma takes place in 2 ethanes: the half-life period is 14-20 hours in the interval from 8 to 24 hours after the drug administration and 41 hours in the interval from 24 to 72 hours, which allows using the drug once a day.

The drug is produced mainly through the intestine in an unchanged form - 50%, a small part is excreted by the kidneys - 6%.

Indications:

Infectious-inflammatory diseases caused by microorganisms susceptible to azithromycin:

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

- infection 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 (erysipelas, impetigo, secondarily infected dermatoses);

- urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis);

- the initial stage of Lyme disease (borreliosis) - migrating erythema (erythema migrans).

Contraindications:

Hypersensitivity to azithromycin, erythromycin, other macrolides or ketolides, or other components of the drug; severe liver function disorders (Child-Pugh class C); severe renal dysfunction (creatinine clearance (CK) less than 40 ml / min); simultaneous administration with ergotamine and dihydroergotamine; children under 12 years of age with a body weight of less than 45 kg; breast-feeding.

Carefully:

Pregnancy; myasthenia gravis; impaired liver function of mild and moderate severity; disturbance of renal function of mild and moderate severity (QC more than 40 ml / min); the patients with the presence of pro-arrhythmic factors (especially in elderly patients) with congenital or acquired lengthening of the interval QT, in patients receiving antiarrhythmic drug therapy classes IA (quinidine, procainamide), III (dofetilide, amiodarone, sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with disturbances of water-electrolyte balance, especially in case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, cardiac arrhythmia or severe heart failure: simultaneous use of warfarin, digoxin, ciclosporin.

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 stopped (excreted in breast milk).

Dosing and Administration:

Inside, 1 hour before or 2 hours after meals 1 time per day.

Adults and children over 12 years of age with a body weight above 45 kg with infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues - 0.5 g (2 capsules) 1 time per day for 1 reception for 3 days (course dose - 1.5 g).

In cases of urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis) - once I g (4 capsules).

With Lyme disease (the initial stage of borreliosis) migrating viewers- (erythema migrans) - I g (4 capsules) on the first day and 0.5 g (2 capsules) daily from 2 to 5 days (course dose - 3 g).

In case of impaired renal function: when used in patients with impaired renal function of mild severity (CC greater than 40 ml / min), dose adjustment is not required.

If there is a violation of the liver: when used in patients with impaired liver function of mild and moderate severity, dose adjustment is not required.

Elderly patients: correction of the dose is not required. Since elderly people may already have current pro-rhythmogenic conditions, caution should be exercised when using AzitRus® because of the high risk of developing cardiac arrhythmias, including pirouette arrhythmias.

Side effects:

The frequency of side effects is classified according to WHO recommendations very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%; The unknown frequency can not be estimated from the available data.

Infectious diseases: infrequently - candidiasis, including mucous membranes of the mouth and genitals, pneumonia, pharyngitis, gastroenteritis, respiratory diseases, rhinitis; unknown frequency - pseudomembranous colitis.

From the side of the blood and lymphatic system: infrequently - leukopenia, neutropenia, eosinophilia; very rarely - thrombocytopenia, hemolytic anemia.

From the side of metabolism and nutrition: infrequently - anorexia

Allergic reactions: infrequently - angioedema, reaction hypersensitivity; an unknown frequency is an anaphylactic reaction.

From the nervous system: often - headache; infrequently - dizziness, paresthesia, a violation of taste sensations, 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 organ of vision: infrequently - impaired vision.

From the side of the hearing organ and labyrinthine disorders: infrequently - hearing disorder, vertigo; unknown frequency - hearing impairment, including deafness and / or tinnitus.

From the cardiovascular system: infrequently - a feeling of palpitations, "tides" of blood to the face; unknown frequency - lowering blood pressure, increasing the interval QT on the electrocardiogram, arrhythmia tina "pirouette", ventricular tachycardia.

From the respiratory system: infrequently - shortness of breath, nosebleed.

From the gastrointestinal tract: very often it is diarrhea; hour then - nausea, vomiting, pain in the abdomen; infrequent - meteorism, dyspepsia, gastritis, constipation, dysphagia, bloating, dryness of the oral mucosa, belching, ulcers of the oral mucosa. increased secretion of salivary glands; very rarely - a discoloration of the tongue, pancreatitis.

From the liver and bile ducts: infrequently - hepatitis, rarely - a violation of the liver, cholestatic jaundice; unknown frequency - hepatic insufficiency (in rare cases with a detailed outcome mainly against a background of severe impairment of liver function), liver necrosis, fulminant hepatitis.

From the skin and subcutaneous tissues: infrequently - skin rash, itching, hives, dermatitis, dry skin, sweating; rarely - the reaction of photosensitization; unknown frequency - Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.

From the musculoskeletal system: infrequently - osteoarthritis, myalgia, pain in the blue, neck pain, unknown frequency - arthralgia

From the side of the kidneys and urinary tract: infrequent dysuria, pain in the kidney, unknown frequency - interstitial nephritis, acute renal failure.

From the genitals and the breast: infrequently - metrorrhagia, dysfunction of testicles.

Other: infrequently - asthenia, malaise, fatigue, face 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 the blood plasma. Infrequent increase in activity of aspartate aminotransferase, alanine aminotransferase, an increase in bilirubin concentration in the blood plasma, an increase in the concentration of urea in the blood plasma, an increase in serum creatinine, a change in the potassium content in the blood plasma, an increase in the activity of alkaline phosphatase in the blood plasma, an increase in the level of chlorine in the blood plasma, increasing blood glucose, increasing the number of platelets, increasing hematocrit, increasing the concentration of bicarbonates in the blood plasma, changing the contents Nia sodium in the blood plasma.

Overdose:

Symptoms: nausea, temporary loss of hearing, vomiting, diarrhea.

Treatment: symptomatic therapy: gastric lavage.

Interaction:

Antacid preparations

Antacid preparations do not affect the bioavailability of azithromycin, but reduce the maximum concentration in blood plasma by 30%, the hollow drug should be taken at least one hour before or two hours after taking these drugs and food.

Cetirizine

Simultaneous use of azithromycin with cetirizine (20 mg each) for 5 days does not lead to a pharmacokinetic interaction and a significant change in the interval QT.

Didanosine (dideoxyinosine)

Simultaneous use of azithromycin (1200 mg / day) and didanosine (400 mg / day) does not lead to changes in pharmacokinetic indications of didanosine.

Digoxin (substrates of P-glycoprotein)

Simultaneous 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 plasma. Thus, with the simultaneous use of azithromycin and digoxin, it is necessary to consider the possibility of increasing the concentration of digoxin in the blood plasma.

Zidovudine

When combined with zidovudine azithromycin (a single dose of 1000 mg and a multiple dose of 1200 mg or 600 mg) have little effect on the pharmacokinetics, including the excretion of zidovudine or its glucuronide metabolite by the kidneys.However, the use of azithromycin causes 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.

Isozymes of cytochrome R₄₅₀

Azithromycin weakly interacts with cytochrome isoenzymes R₄₅₀. It was not revealed that azithromycin participates in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin is not an inhibitor and inducer of cytochrome isoenzymes R₄₅₀.

Alkaloids of ergot

Given the theoretical possibility of the emergence of ergotism, the simultaneous use of azithromycin with derivatives of ergot alkaloids, pharmacokinetic studies of the simultaneous use of azithromycin and preparations metabolized with the participation of cytochrome P450 isoenzymes were not recommended.

Atorvastatin

Simultaneous use of atorvastatin (10 mg daily) and azithromycin (500 mg daily) does not lead to changes in the concentrations of atorvastatin in the blood plasma (based on the inhibition of GMK-CoA reductase). However, separate reports have been received about cases of rhabdomyolysis in patients taking concomitantly azithromycin and statins.

Carbamazepine

There was no significant effect on the concentration of carbamazepine and its active metabolite in blood plasma in patients receiving concomitantly azithromycin.

Cimetidine

There was no effect of a single dose of cimetidine on the pharmacokinetics of azithromycin, provided cimetidine is used for 2 hours to azithromycin.

Anticoagulants of indirect action (coumarin derivatives)

In pharmacokinetic studies azithromycin did not affect the anticoagulant effect of a single dose of 15 mg of warfarin. Potential anticoagulation was reported after simultaneous use of azithromycin and anticoagulantgindirect reactants (coumarin derivatives). Although a causal relationship has not been established, consideration should be given to the need for frequent monitoring of prothrombin time when azithromycin is used in patients who receive oral anticoagulants of indirect action (coumarin derivatives).

Cyclosporin

With the simultaneous use of azithromycin (500 mg / day once) and cyclosporine (10 mg / kg / day once) for 3 days there is an increase in the maximum concentration in the blood plasma (Cmax) and the area under the "concentration-time" curve (AUC_0-5) cyclosporine. Caution should be exercised when using drugs at the same time, it is necessary to monitor the concentration of cyclosporine in the blood plasma and, accordingly, adjust the dose.

Efavirenz

Simultaneous use of azithromycin (600 mg / day once) and efavirenz (400 mg / day) daily for 7 days does not cause any clinically significant pharmacokinetic interaction.

Fluconazole

The simultaneous use of azithromycin (1200 mg once) and fluconazole (800 mg once) does not change the pharmacokinetics of the latter. The total exposure and the half-life of azithromycin do not change, but a decrease in Cmah azithromycin (by 18%), which has no clinical significance.

Indinavir

Simultaneous use of azithromycin (1200 mg once) does not cause a statistically significant effect on the pharmacokinetics of indinavir (800 mg 3 times / day for 5 days).

Methylprednisolone

Azithromycin does not significantly affect the pharmacokinetics methylprednisolone.

Nelfinavir

Simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3twice a day) causes an increase in the equilibrium concentration of azithromycin in the blood plasma. No clinically significant side effects were observed, and a dose adjustment of azithromycin with its simultaneous application with nelfinavir is not required.

Rifabutin

Simultaneous use of azithromycin and rifabutin does not affect the concentration of each drug in the blood plasma. With the simultaneous use of azithromycin and rifabutin, neutropenia was sometimes observed. Despite the fact that neutropenia was associated with rifabutin, a causal relationship between the combination of these drugs and neutropenia has not been established.

Sildenafil

With simultaneous application, no effect of azithromycin (500 mg / day per day for 3 days) on AUC and Cmah sildenafil or its main circulating metabolite.

Terfenadine

In pharmacokinetic studies, no evidence was found for the interaction between azithromycin and terfenadine. Individual cases were reported where the possibility of such interaction could not be ruled out completely, but there was not one concrete proof that such an interaction took place.It was found that the simultaneous use of terfenadine and macrolides may cause arrhythmia and lengthening of the interval QT.

Theophylline

There was no interaction between azithromycin and theophylline.

Triazolam / midazolam

Significant changes in pharmacokinetic parameters with the simultaneous use of azithromycin with triazolam or midazolam in therapeutic doses are not revealed.

Trimethoprim / sulfamethoxazole

Simultaneous use of trimethoprim / sulfamethoxazole with azithromycin did not reveal a significant effect on Cmah, total exposure or excretion of the kidneys of trimethoprim or sulfamethoxazole. The concentrations of azithromycin in the blood plasma were consistent with those found in other studies.

Special instructions:

Do not take with food.

In case of missed intake of a single dose of the drug, the missed dose should be taken as soon as possible, and the following - with interruptions of 24 hours.

The drug AzitRus^® should be taken at least 1 hour before or 2 hours after taking antacid preparations.

The drug AzitRus® should be used with caution to patients with impaired liver function of mild to moderate severity 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, therapy with AsitRus® should be discontinued and a functional condition of the liver should be investigated.

When violations of kidney function of mild and moderate severity (QC more than 40 ml / min) therapy with the drug AsitRus^® follow with caution under the control of the state of kidney function.

As with the use of other antibacterial drugs, patients with AsitRus® should regularly examine patients for non-susceptible microorganisms and signs of development of superinfections, including fungal ones. The drug AzitRus^® do not use longer courses than indicated in the instructions, since the pharmacokinetic properties of azithromycin allow us to recommend a short and simple dosing regimen.

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, this combination is not recommended.

With the long-term administration of the drug AsitRus®, the development of pseudomembranous colitis, caused by Clostridium difficile, as in the form of mild diarrhea, and severe colitis. With the development of antibiotic-associated diarrhea against the background of taking AzitRus®, and also through 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded. Drugs that inhibit the intestinal peristalsis are contraindicated.

When treating macrolides, including azithromycin, prolonged cardiac repolarization and interval QT, increasing the risk of developing cardiac arrhythmias, including arrhythmias such as pirouettes.

Caution should be used when using AzitRus® in patients with pro-arrhythmic factors (especially in elderly patients) with congenital or the acquired lengthening interval QT, in patients receiving antiarrhythmic drugs of classes 1A (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with disturbances of water-electrolyte balance, especially in case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, cardiac arrhythmia or severe heart failure.

The use of the drug AzitRus® can be provoked, the development of myasthenic syndrome or cause an exacerbation of myasthenia gravis.

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

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:Capsules 250 mg.

Packaging:

6 or 10 capsules in a planar cell packaging made of polyvinylchloride film and aluminum foil printed lacquered.

1, 2 contour mesh packages with instructions for use in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N001561 / 01

Date of registration:15.02.2008 / 21.10.2013

Expiration Date:Unlimited

The owner of the registration certificate:SYNTHESIS, OJSC SYNTHESIS, OJSC Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Information update date: & nbsp22.06.2017

Illustrated instructions

Instructions

AzitrRus® (AzitRus®)