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

pregelatinized starch 145.3 mg, crospovidone 40.0 mg, calcium hydrophosphate anhydrous 176.6 mg, sodium lauryl sulfate 4.7 mg, magnesium stearate 9.4 mg;

shell: hypromellose - 22.0 mg, titanium dioxide - 5.6 mg, lactose monohydrate - 3.0 mg, triacetin - 4.4 mg.

Description:The tablets covered with a film membrane, white, capsular-shaped, biconvex, with a risk on one side. On the cross section, the core of the tablet is white or almost white in color.

Pharmacotherapeutic group:Antibiotic - azalide

ATX: & nbsp

J.01.F.A.10 Azithromycin

Pharmacodynamics:

Antibacterial agent of a wide spectrum of action, azalide, acts bacteriostatically. Communicating with 50S subunit of ribosomes, inhibits peptidranslokase at the stage of translation, suppresses protein synthesis, slows the growth and multiplication of bacteria, has a bactericidal effect at high concentrations.

Pharmacodynamics

Effects on extracorporeal and intracellular pathogens.

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

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

Sensitive: aerobic gram-positive microorganisms: Streptococcus pneumoniae (penicillin-sensitive), Streptococcus pyogenes, Staphylococcus aureus (methicillin-sensitive);

aerobic gram-negative microorganisms: Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, Haemophilus parainfluenzae Pasteurella multocida. Neisseria gonorrhoeae;

anaerobic microorganisms: Prevotella spp., Clostridium perfringens, Fusobacterium spp., Porphyromonas spp.;

Other: Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.

Moderately sensitive or insensitive: aerobic gram-positive microorganisms - Streptococcus pneumoniae (moderately sensitive or resistant to penicillin).

Stable: aerobic gram-positive microorganisms - Enterococcus faecalis, Staphylococcus spp. (methicillin-resistant), anaerobic microorganisms - Group Bacteroides ffagilis.

Streptococcus pneumoniae, beta-hemolytic Streptococcus spp. groups A, Enterococcus faecalis and Staphylococcus aureus (including methicillin-resistant strains), resistant to erythromycin and other macrolides, lincosamides, are resistant to azithromycin.

Pharmacokinetics:

Absorption is high, acid-fast, lipophilic. Bioavailability after a single intake of 0.5 g - 37% (the effect of "first passage" through the liver), the maximum concentration after oral intake of 0.5 g - 0.4 mg / l, the time to reach the maximum concentration - 2.5-2.9 h; in tissues and cells the concentration is 10-50 times higher than in serum, the volume of distribution is 31.1 l / kg.

Easily passes the histohematological barriers. It penetrates well into the respiratory tract, genito-urinary organs and tissues, incl. in the prostate gland, in the skin and soft tissues. It penetrates through cell membranes and creates high concentrations in them, accumulates in lysosomes (which is especially important for the eradication of intracellularly located pathogens). It is also transported by phagocytes: polymorphonuclear leukocytes and macrophages.

Concentration in the foci of infection is significantly higher (by 24-34%) than in healthy tissues, and correlates with the severity of inflammatory edema. Saved in effective concentrations within 5-7 days after taking the last dose. Communication with plasma proteins is 7-50% (inversely proportional to the concentration in blood).

In the liver, demethylated, inactive metabolites are formed. In the metabolism of the drug, isozymes participate CYP3A4, CYP3A5, CYP3A7, of which it is an inhibitor. Plasma clearance - 630 ml / min. The half-life (T1 / 2) between 8 and 24 hours after admission is 14-20, 4, T₁/₂ in the interval from 24 to 72 h -41 h. 50% is excreted with bile in unchanged form, 6% - in kidneys.

Eating significantly changes the pharmacokinetics: maximum, concentration (Cmax) and area under the curve "concentration-time" (AUC) are reduced by 52% and 43% respectively.

In elderly men (65-85 years) pharmacokinetic parameters do not change, in women it increases FROMmOh (by 30-50%), in children aged 1-5 years decrease FROMmOh, T1/2, AUC.

Indications:

Infectious-inflammatory diseases caused by microorganisms susceptible to azithromycin: infections of the upper respiratory tract and ENT organs (pharyngitis, tonsillitis, sinusitis, otitis media); infections of the lower respiratory tract (pneumonia (including caused by atypical pathogens), bronchitis); infections of the skin and soft tissues (acne vulgaris (medium st.gravity), erysipelas, impetigo, secondarily infected dermatoses); urinary tract infections (urethritis, cervicitis (caused by Chlamydia trachomatis)); Lyme disease (initial stage - erythema migrans).

Contraindications:

Hypersensitivity to azithromycin (including other macrolides), components of the drug, severe hepatic insufficiency (class B and C on the Child-Pugh scale), severe renal failure (creatinine clearance less than 40 mL / min), simultaneous use with ergotamine and dihydroergotamine , lactation period, children under 12 years of age with a body weight of less than 45 kg (for this dosage form), lactose intolerance, lactase deficiency, glucose-galactose malabsorption (due to the presence of lactose).

Carefully:

Renal failure (creatinine clearance more than 40 ml / min), hepatic insufficiency (class A on the Child-Pugh scale), arrhythmia, incl. predisposition to arrhythmia and lengthening of the interval Q-T (risk of ventricular arrhythmia and lengthening of the interval Q-T), myasthenia gravis, simultaneous reception terfenadine, warfarin, digoxin; simultaneous reception of drugs, extending the interval Q-T.

Pregnancy and lactation:

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

During lactation during the treatment should stop breastfeeding.

Dosing and Administration:

Adults and children over 12 years of age with a body weight of more than 45 kg: inside, 1 hour before or 2 hours after meals 1 time per day; infection of the upper and lower respiratory tract; ENT organs, skin and soft tissues - 0.5 g / day for 1 reception for 3 days (exchange dose - 1.5 g); when acne vulgaris - 0.5 g / day for 1 reception for 3 days, then 0.5 g / day 1 time per week for 9 weeks. The first pill to be taken weekly after 7 days after the first pill daily (day 8 from the start of treatment), the next 8 weekly tabs - with an interval of 7 days.

In infections of the urinary tract (urethritis or cervicitis caused by Chlamydia trachomatis) - once 1 g.

With Lyme disease - for treatment I Art. (erythema migrans) - 1 g on the first day and, 0.5 g daily from 2 to 5 days (course dose - 3 g).

For patients with moderate impairment of kidney function (creatinine clearance more than 40 ml / min), dose adjustment is not needed.

Side effects:

From the hematopoiesis: lymphopenia, eosinophilia, hemolytic anemia, leukopenia, neutropenia, thrombocytopenia.

From the nervous system: paresthesia, taste disorders, hypoesthesia, aggression, syncope, convulsions, psychomotor hyperactivity, loss of smell, myasthenia gravis.

From the sense organs: impaired clarity of visual perception, deafness, noise in the ears.

From the cardiovascular system: lowering blood pressure, increasing the interval Q-T, arrhythmia such as "pirouette", ventricular tachycardia.

From the digestive system: dyspepsia, discoloration of the tongue, hyperbilirubinemia, hepatitis, pancreatitis, pseudomembranous colitis, liver dysfunction, hepatic insufficiency (in rare cases with fatal outcome, mainly on the background of liver dysfunction), liver necrosis, fulminant hepatitis.

Allergic reactions: Anaphylactic reaction, including edema (in rare cases, fatal), erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the genitourinary system: increase of residual urea nitrogen and creatinine concentration in blood plasma, interstitial nephritis,acute renal failure.

Other: weakness, peripheral edema, malaise; hyperglycemia, arthralgia.

Overdose:

Symptoms: severe nausea, temporary loss of hearing, vomiting, diarrhea. Treatment: symptomatic.

Interaction:

Antacids (aluminum and magnesium-containing) do not affect bioavailability, but reduce the concentration of azithromycin in the blood by 30%, so the interval between their intake should be 1; h before or 2 hours after taking these drugs.

With simultaneous use with derivatives of ergotamine and dihydroergotamine, toxic effects (vasospasm, dysesthesia) of the latter are possible.

When combined with anticoagulants indirect effect of the coumarin series (warfarin) and azithromycin (in usual doses) patients need careful monitoring of prothrombin time.

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

When used simultaneously with cyclosporine, the concentration of cyclosporin in the blood should be monitored.

With simultaneous use with digoxin, it is necessary to control the concentration of digoxin in the blood (there may be an increase in absorption of digoxin in the intestine).

At simultaneous application with nelfinavir it is possible to increase the incidence of adverse reactions of azithromycin (decrease in hearing, increase of activity of "liver" transaminases).

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

Consideration should be given to the possibility of inhibiting the azithromycin SURCA4 isoenzyme when used simultaneously with cyclosporine, terfenadine, ergot alkaloids, cisapride, pimozide, quinidine, astemizole, and other drugs whose metabolism occurs with the participation of this enzyme.

Azithromycin does not affect the concentration of carbamazepine, cimetidine, didanosine, efavirenz, fluconazole, indinavir, midazolam, theophylline, triazolam, trimethoprim / sulfamethoxazole, cetirizine, sildenafil, atorvastatin, rifabutin and methylprednisolone in the blood together.

Special instructions:

In case of missed dose, the missed dose should be taken as soon as possible, and the subsequent dose should be taken at intervals of 24 hours.

Azithromycin should be taken 1 hour before or 2 hours after taking antacid. medicines.

Take with caution patients with hepatic insufficiency because of the possibility of developing fulminant hepatitis and severe hepatic insufficiency in such patients. In the presence of symptoms of liver dysfunction (rapidly increasing asthenia, jaundice, darkening of the urine, a tendency to bleeding, hepatic encephalopathy) therapy with azithromycin should be discontinued and an examination of the functional state of the liver should be carried out.

With moderate renal failure (creatinine clearance more than 40 ml / min), azithromycin should be administered under the control of kidney function.

Contraindicated simultaneous administration of azithromycin with derivatives of ergotamine and dihydroergotamine because of the possible development of ergotism.

When using the drug both in the background and 2-3 weeks after discontinuation of treatment, it is possible to develop diarrhea caused by Clostridium difficile (pseudomembranous colitis). In mild cases, it is sufficient to cancel, treat and apply ion-exchange resins (colestramine, colestipol), in severe cases, compensation for loss of fluid, electrolytes and protein, the appointment of vancomycin, bacitracin or metronidazole.

Do not use drugs that inhibit the intestinal motility. Since it is possible to extend the interval Q-T in patients receiving macrolides, including azithromycin, with the use of azithromycin, caution should be exercised in patients with known risk factors for lengthening the interval Q-T: elderly age; violation of electrolyte balance (hypokalemia, hypomagnesemia); syndrome, congenital lengthening interval Q-T; heart disease (heart failure, myocardial infarction, bradycardia); simultaneous reception of drugs that can lengthen the interval Q-T (including antiarrhythmic drugs Ia and III classes, tricyclic and tetracyclic antidepressants, neuroleptics, fluoroquinolones).

With the use of azithromycin, the development of myasthenic syndrome or myasthenia exacerbation is possible.

Effect on the ability to drive transp. cf. and fur:During the treatment period, care must be taken when driving vehicles and engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

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

Packaging:

3 tablets per contour cell pack Al / PVC.

1 circuit cell pack together with the instruction for use is placed in a pack of cardboard.

Storage conditions:

In dry, dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use after the specified time on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001032