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

auxiliary matter: lactose monohydrate - 61.98 mg; cellulose microcrystalline - 40,60 mg; magnesium stearate - 3.70 mg; povidone low molecular weight (polyvinylpyrrolidone low molecular weight) - 1.00 mg; sodium lauryl sulfate - 0.70 mg;

hard gelatine capsules: titanium dioxide - 2.0%, gelatin - up to 100%.

Description:

Hard gelatin capsules № 0 of white color. The contents of the capsules are white or white powder with a light yellow hue of color. Conglomerates are allowed, which when pressed with a glass rod are easily converted into free-flowing powder.

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 50Ssubunit of the ribosome, inhibits peptidranslokase at the stage of translation and suppresses 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.

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

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

Microorganisms	MIC, mg / l
Microorganisms	sensitive	sustainable
Staphylococcus	< 1	>2
Streptococcus A, B, C, G	<0,25	>0.5
S. pneumoniae	<0,25	>0,5
N. influenzae	<0,12	> 4
M. catarrhalis	<0,5	>0,5
N. gonorrhoeae	<0,25	>0,5

In most cases, azithromycin is sensitive:

- aerobic Gram-positive microorganisms: Staphylococcus aureus (methicillin-sensitive), Streptococcus pneumoniae (penicillin-sensitive), Streptococcus pyogenes, Streptococcus groups A, B, C, G;

- aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis, Pastcurella 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 that can develop resistance to azithromycin:

- Streptococcus pneumoniae (penicillin-resistant).

Microorganisms initially resistant to azithromycin:

- aerobic Gram-positive microorganisms: Enterococcus faecalis, Staphylococcus spp. (methicillin-resistant staphylococci with very high frequency have acquired resistance to macrolides);

- Gram-positive bacteria resistant to erythromycin;

- anaerobes: Bacteroides fragilis.

Pharmacokinetics:

After oral administration azithromycin well absorbed and quickly distributed in the body. After a single dose of 500 mg bioavailability - 37% (the effect of "first pass"), the maximum concentration in the blood (0.4 mg / l) is created after 2-3 hours, the apparent volume of distribution is 31.1 l / kg, protein binding The blood plasma is inversely proportional to the concentration in the blood and is 7-50%. Penetrates through cell membranes (effective in infections caused by intracellular pathogens), transported by phagocytes to the site of infection, where it is released in the presence of bacteria. Easily passes the histohematological barriers and enters the tissues. Concentration in tissues and cells is 10-50 times higher than in plasma, and in the focus of infection - 24-34% more than in healthy tissues.

In azithromycin, a very long half-life is 30-50 hours. The half-life of the tissues is much larger. The therapeutic concentration of azithromycin is maintained up to 5-7 days after the last dose. Azithromycin is output mainly in the unchanged form - 50% of the intestine, 6% of the kidneys. In the liver, demethylated, losing activity.

Indications:

ANDInfectious-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 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, macrolides, ketolides or other components of the drug;

- severe hepatic insufficiency (Child-Pugh class C);

- severe renal dysfunction (creatinine clearance (CK) less than 40 ml / min);

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

- the period of breastfeeding;

- simultaneous administration with ergotamine and dihydroergotamine;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Carefully:

Myasthenia gravis; violations of liver function of mild and moderate severity; renal dysfunction of mild and moderate severity (QC more than 40 ml / min); elderly patients; in patients with proarrhythmogenic 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 and sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin, 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 digoxin, warfarin, cyclosporine.

Pregnancy and lactation:

In pregnancy, the drug Azithromycin apply only if the intended benefit to the mother exceeds the potential risk to the fetus. If it is necessary to use the drug during breastfeeding, it is recommended to suspend breastfeeding.

Dosing and Administration:

Inside, once a day, but at least 1 hour before or 2 hours after meals.

Adults (including the elderly) and children over 12 years of age with a body weight of over 45 kg

For infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues: 500 mg (2 capsules) once a day for 3 days (course dose - 1.5 g).

With Lyme disease (the initial stage of borreliosis) - migratory erythema (erythema migrans) once a day for 5 days: 1st day - 1.0 g (4 capsules), then from the 2nd to the 5th day - 500 mg (2 capsules) (course dose - 3.0 g) .

In cases of urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis): uncomplicated urethritis or cervicitis - once 1.0 g (4 capsules).

Ppatients with impaired renal function

In patients with impaired renal function of mild and moderate severity (CC greater than 40 ml / min), dose adjustment is not required.

Patients with impaired hepatic function

If the liver function is mild and moderate, dosage adjustment is not required.

Elderly patients

Correction of the dose is not required. Since older patients may have ongoing pro-rhythmogenic conditions, caution should be exercised when using the drug Azithromycin in connection with a high risk of developing cardiac arrhythmias, including arrhythmias such as pirouettes.

Side effects:

Classification of the incidence of side effects according to the recommendations of the World Health Organization (WHO): very often> 1/10; often> 1/100, <1/10; infrequently > 1/1000, < 1/100; rarely> 1/10000, <1/1000; very rarely <1/10000, including individual messages; the frequency is unknown - it is not possible to establish the frequency of occurrence from the available data.

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

From the side of metabolism and nutrition: infrequently - anorexia.

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

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

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

From the nervous system: often - headache; infrequently - dizziness, paresthesia, a violation of taste sensations, drowsiness, insomnia, nervousness; rarely - agitation; frequency unknown - hypoesthesia, 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; frequency unknown - hearing impairment, including deafness and / or tinnitus.

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

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

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

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

From the osteomuscular system and connective tissue: infrequently - osteoarthritis, myalgia, back pain, neck pain; frequency unknown - arthralgia.

From the genitourinary system: infrequently - dysuria, pain in the kidney, metrorrhagia, dysfunction of the testicles; frequency unknown - interstitial nephritis, acute renal failure.

Laboratory indicators: 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; infrequently - increased activity of aspartate aminotransferase, alanine aminotransferase.an increase in the concentration of bilirubin in 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, an increase in the concentration of glucose in the blood, an increase in the number of platelets, an increase in hematocrit, bicarbonates in blood plasma, a change in the sodium content in blood plasma, an increase in the concentration of urea in the blood plasma.

Other: infrequently - asthenia, malaise, fatigue, face swelling, chest pain, fever, peripheral edema.

Overdose:

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

Treatment: symptomatic.

Interaction:

Antacid preparations

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 or eating food.

Cetirizine

Simultaneous 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 interval QT.

Didanosine (dideoxyinosine)

Simultaneous use of azithromycin (1200 mg / day) and didanosine (400 mg / day) in 6 HIV-infected patients showed no change in the pharmacokinetic indications of didanosine compared with the placebo group.

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 has little effect on the pharmacokinetics, including kidney excretion, zidovudine or its glucuronide metabolite.

Pharmacokinetic studies of the simultaneous use of azithromycin and drugs whose metabolism occurs with the participation of cytochrome P450 isoenzymes have been carried out. 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 inhibitor and inducer of cytochrome P450 isoenzymes.

Atorvastatin

The simultaneous use of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause a change in the concentrations of atorvastatin in the blood plasma (based on the inhibition of GMA-CoA reductase). However, separate reports were received on cases of rhabdomyolysis in patients receiving concomitantly azithromycin and statins.

Carbamazepine

In pharmacokinetic studies involving healthy volunteers, ns revealed a significant effect on the concentration of carbamazepine and its active metabolite in blood plasma in patients receiving concomitantly 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 have been observed, provided cimetidine is administered 2 hours before 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 taken by healthy volunteers. Potential anticoagulant effect was reported after simultaneous use of azithromycin and indirect anticoagulants (coumarin derivatives). Although no causal relationship has been established, the need to conduct frequent prothrombin time monitoring with azithromycin in patients who receive oral anticoagulants of indirect action (coumarin derivatives) should be considered.

Cyclosporin

In a pharmacokinetic study involving healthy volunteers who were ingested for three days azithromycin (500 mg / day once), and then ciclosporin (10 mg / kg / day once), there was a significant increase in the maximum concentration in the blood plasma (C_m_Oh) and the area under the curve "concentration-time" (AUC0.5) cyclosporine. Care should be taken when using these drugs at the same time. In case of simultaneous use of these drugs, 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 did not cause any clinically significant with the pharmacokinetic interaction.

Fluconazole

The simultaneous use of azithromycin (1200 mg once) did not change (the pharmacokinetics of fluconazole (800 mg once) .The total exposure and half-life of azithromycin did not change with simultaneous application of fluconazole, but there was a decrease in C_m_Oh azithromycin (by 18%), that ns had clinical significance.

Indinavir

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

Methylprednisolone

Azithromycin does not significantly affect the pharmacokinetics of methylprednisolone.

Nelfinavir

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. Correction of a dose of azithromycin when it is used simultaneously 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 the use of rifabutin, a causal relationship between the use of a combination of azithromycin and rifabutin and neutropenia has not been established.

Sildenafil

When used in healthy volunteers, evidence of the effect of azithromycin (500 mg / day daily for 3 days) on AUC and C_m_a_x sildenafil or its main circulating metabolite.

Terfenadine

3 pharmacokinetic studies did not provide evidence of 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 C_m_Oh, total exposure or renal excretion of trimethoprim or sulfamethoxazole. The concentrations of azithromycin in the blood plasma were consistent with those found in other studies.

Alkaloids ergot

Given the theoretical possibility of the emergence of ergotism, the simultaneous use of azithromycin with derivatives of ergot alkaloids is not recommended.

Special instructions:

In case of missing one dose of the drug Azithromycin The missed dose should be taken as soon as possible, and the subsequent dose with interruptions of 24 hours.

A drug Azithromycin should be taken at least one hour before or two hours after taking antacid preparations.

A drug Azithromycin should be taken with caution to patients with impaired liver function of mild and moderate severity because of the possibility of developing fulminant hepatitis and severe hepatic insufficiency.

In the presence of symptoms of impaired liver function, such as rapidly increasing asthenia, jaundice, darkening of the urine, a tendency to bleeding, hepatic encephalopathy, drug therapy Azithromycin it is necessary to stop and conduct a study of the functional state of the liver.

For violations of kidney function of mild and moderate severity (CC more than 40 ml / min), drug therapy Azithromycin should be performed with caution, under the control of the state of kidney function.

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

A drug Azithromycin 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 due to the development of ergotism with the simultaneous use of macrolides with derivatives of ergotamine and dihydroergotamine, this combination is contraindicated.

With prolonged intake of the drug Azithromycin possibly 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 on the background of taking the drug Azithromycin, and also 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded. The use of drugs that inhibit intestinal peristalsis is contraindicated.

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

Care should be taken when using the drug Azithromycin in patients with proarrhythmogenic 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 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.

Application of the drug Azithromycin can 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:

Capsules 250 mg.

Packaging:

6 or 10 capsules in a contour cell box made of a polyvinylchloride film and aluminum foil.

6 capsules in a jar of high-density polyethylene.

1 contour squad package of 6 capsules, 1 circuit pack of 10 capsules or one jar along with instructions for medical 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:

3,5 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:P N002599 / 01

Date of registration:07.08.2008

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Information update date: & nbsp24.08.2015

Illustrated instructions

Instructions

Azithromycin (Azithromycin)