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

Excipients: pregelatinized starch (Starch 1500) 40.00 mg, hydroxypropyl cellulose 70.00 mg, sodium lauryl sulfate 5.00 mg, calcium hydrophosphate dihydrate 135.50 mg, croscarmellose sodium 9.00 mg, anhydrous lactose 96.00 mg, silicon dioxide colloidal anhydrous 0.50 mg, magnesium stearate 20.00 mg;

film sheath: opedraj® white Y-1-7000 - 30,00 mg (hypromellose - 18,75 mg, macrogol 400 - 1,875 mg, titanium dioxide (E171) - 9,375 mg).

Description:

Oblong biconvex tablets, coated with a white film membrane, with a dividing risk on one side.

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. By binding to the 50S subunit of the ribosome, it inhibits the peptidranslokase at the translation stage 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, anaerobes, intracellular and other microorganisms.

Microorganisms can initially be resistant to the action of an antibiotic or 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
Streptococcus pneumoniae	≤0, 25	>0,5
Haemophilus influenzae	≤0,12	>4
Moraxella catarrhalis	≤0,5	>0,5
Neisseria gonorrhoeae	≤0,25	>0,5

In most cases, the drug Zyromin is active against the following microorganisms:

1. Gram-positive aerobes

Staphylococcus aureus (methicillin-sensitive strains)

Streptococcus pneumoniae (penicillin-sensitive strains)

Streptococcus pyogenes;

2. Gram-negative aerobes

Haemophilus influenzae

Haemophilus parainfluenzae

Legionella pneumophila

Moraxella catarrhalis

Pasteurella multocida

Neisseria gonorrhoeae

3. Anaerobes

Clostridium perfringens

Fusohacterium spp.

Prevotella spp.

Porphyromonas spp.

4. Other microorganisms

Chlamydia trachomatis

Chlamydia pneumoniae

Chlamydia psittaci

Mycoplasma pneumoniae

Mycoplasma hominis

Borrelia burgdorferi

Microorganisms capable of developing resistance to azithromycin

Gram-positive aerobes

Streptococcus pneumoniae (penicillin-resistant strains)

Initially, resistant microorganisms

Gram-positive aerobes

Enterococcus faecalis

Staphylococcus spp. (methicillin-resistant strains of staphylococcus exhibit a very high degree of resistance to macrolides)

Gram-positive bacteria resistant to erythromycin.

Anaerobes

Bacteroides fragilis.

Pharmacokinetics:

Suction

After oral administration azithromycin well absorbed and quickly distributed in the body. After a single dose of 500 mg bioavailability is 37% (due to the effect of "first pass" through the liver). The maximum concentration (0.4 mg / l) in the blood is created after 2-3 hours.

Distribution

Apparent volume of distribution of 31.1 l / kg, binding to 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. Easily penetrates through the histohematological barriers and enters the tissues. The concentration of azithromycin 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.

Metabolism

Azithromycin is demethylated in the liver, losing activity.

Excretion

In azithromycin, a very long half-life is 35-50 hours. The half-life of tissues is much longer.The therapeutic concentration of azithromycin persists up to 5-7 days after the last dose. Azithromycin output, at mostly, unchanged - 50% through the intestine, 6% by the kidneys.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to the preparation:

- Infections of the upper respiratory tract and ENT - organs (pharyngitis / tonsillitis, sinusitis, 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 (erysipelas, impetigo, secondarily infected dermatoses, acne vulgaris of moderate severity);

- The initial stage of Lyme disease (borreliosis) - migrating erythema (erythema migrans);

- Urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis).

Contraindications:

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

- impaired hepatic function;

- Children under 12 years of age with a body weight of less than 45 kg (for this dosage form and dosage);

- simultaneous administration with ergotamine and dihydroergotamine;

- rare hereditary intolerance to galactose, lactase deficiency, glucose-galactose malabsorption syndrome (the preparation contains lactose).

Carefully:

Myasthenia gravis; impaired liver function of mild and moderate severity; terminal renal failure with GFR (glomerular filtration rate) less than 10 ml / min; the patients with the presence of pro-arrhythmogenic factors (especially in elderly patients): with congenital or acquired lengthening interval QT, in patients receiving therapy with antiarrhythmic drugs classes IA (quinidine, procainamide) or III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with disturbances of water-electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, cardiac arrhythmia or severe heart failure; at simultaneous use of digoxin, warfarin, cyclosporine.

Pregnancy and lactation:

During pregnancy and during breastfeeding, the use of the drug is possible only in the event that,if the expected potential benefit of therapy for the mother is greater than the potential risk to the fetus and the baby.

If you need to use the drug Zyromin during lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside, not liquid, at least 1 hour before or 2 hours later after eating, 1 time per day.

With infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues: 1 tablet (500 mg) once a day for 3 days (course dose of 1.5 g).

With 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 6.0 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 next 8 weekly tablets should be taken at intervals of 7 days.

With Lyme disease (the initial stage of borreliosis) - migratory erythema (erythema migrans) the drug is prescribed 1 time per day for 5 days: on the 1st day - in a dose of 1.0 g (2 tablets of 500 mg), then from 2 to 5 days - 1 tablet (500 mg) once a day (exchange dose of 3.0 g).

With infections of the urogenital tract, caused by Chlamydia trachomatis (urethritis, cervicitis): with uncomplicated urethritis / cervicitis, the drug is used in a dose of 1 g (2 tablets of 500 mg) once.

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

Special patient groups

In case of impaired renal function: in patients with GFR 10-80 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. Because older people can already have current proaritmogenic conditions, care should be taken when use of Zyromin in connection with a high risk of cardiac arrhythmia, including polymorphic ventricular tachycardia of the "pirouette" type.

Side effects:

The frequency of side effects is classified according to the recommendations of the World Health Organization (WHO): 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%; frequency is unknown - can not be estimated from the available data.

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

Violations from the blood and lymphatic system: infrequently - leukopenia, neutropenia, eosinophilia; very rarely - thrombocytopenia, hemolytic anemia.

Disorders from the metabolism and nutrition: infrequently - anorexia.

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

Impaired nervous system: often - headache; infrequently - dizziness, dyspnoea, paresthesia, 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.

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

Hearing disorders and labyrinthine disturbances: infrequently - hearing disorder, vertigo; frequency unknown - hearing impairment, incl. deafness and / or tinnitus.

Disorders from the cardiovascular system: infrequent - a feeling of palpitation, a tide of blood to the face; frequency unknown - lowering blood pressure, increasing the interval QT on the electrocardiogram, polymorphic ventricular tachycardia of the "pirouette" type, ventricular tachycardia.

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

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

Disorders 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 on the background of severe impairment of liver function); liver necrosis, fulminant hepatitis.

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

Disorders from the musculoskeletal system: infrequently - osteoarthritis, myalgia, back pain, neck pain; frequency unknown - arthralgia.

Disorders from the kidneys and urinary tract: infrequently - dysuria, pain in the kidney; frequency unknown - interstitial nephritis, acute renal failure.

Violations of the genitals and 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; infrequently - increased activity of aspartate aminotransferase (ACT), alanine aminotransferase (ALT) in blood plasma, increased bilirubin concentration in blood plasma,increase in the concentration of urea in the blood plasma, increasing the concentration of creatinine in the blood plasma, changing the potassium content in the blood plasma, increasing the activity of alkaline phosphatase in the blood plasma, increasing the level of chlorine in the blood plasma, increasing the concentration of glucose in the blood, increasing the number of platelets, increasing hematocrit, the concentration of bicarbonates in the blood plasma, the change in the content of sodium in the blood plasma.

Overdose:

The side effects that occur with an azithromycin overdose are the same as the side effects observed when taking the drug at recommended therapeutic doses. Typical symptoms of overdose are: nausea, vomiting, diarrhea, temporary hearing loss. In case of an overdose, general symptomatic and supportive treatment is used. There is no antidote.

Interaction:

Antacid preparations

Antacid preparations do not affect bioavailability azithromycin, but reduce the maximum concentration in the blood by 30%, so the drug Zyromin 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) 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 six 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, incl. azithromycin, with P-glycoprotein substrates, such as digoxin, leads to an increase in the concentration of substrate P-glycoprotein in the blood serum. Thus, with the simultaneous use of azithromycin and digoxin, it is necessary to take into account the possibility of increasing the concentration of digoxin in the blood serum.

Zidovudine

Simultaneous use of azithromycin (a single dose of 1000 mg and repeated administration of 1200 or 600 mg) has a slight effect on the pharmacokinetics, including. kidney removal of zidovudine or its glucuronide metabolite. However, the use of azithromycin caused an increase in the concentration of phosphorylatedzidovudine, a clinically active metabolite in peripheral blood mononuclear cells. The clinical significance of this fact is unclear.

Alkaloids of ergot

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

Preparations metabolized with the participation of cytochrome P450 isoenzymes

Azithromycin weakly interacts with isoenzymes of the cytochrome system P450.He 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.

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

Atorvastatin

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

Carbamazepine

In pharmacokinetic studies involving healthy volunteers, there was no 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 detected, 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 warfarin when administered in a single dose of 15 mg by healthy volunteers. Potential anticoagulant effect was reported after simultaneous use of azithromycin and indirect anticoagulants (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

In a pharmacokinetic study involving healthy volunteers who within 3 days were ingested azithromycin (500 mg / day once), and then ciclosporin (10 mg / kg / day once), there was a significant increase in C_m_Oh in blood plasma and AUC0-5 cyclosporine. Care should be taken when using these drugs at the same time. In case of necessity of simultaneous application 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 pharmacokinetic interaction.

Fluconazole

Simultaneous use of azithromycin (1200 mg once) did not change the pharmacokinetics of fluconazole (800 mg once). The total exposure and the half-life of azithromycin did not change with the simultaneous use of fluconazole, but a decrease in C_m_Oh azithromycin (by 18%), which had no clinical significance.

Indinavir

Simultaneous use of azithromycin (1200 mg once) does nothad 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 concentrations of azithromycin in the blood serum. Clinically significant side effects were not observed, and dosage adjustment of azithromycin when it is used concomitantly with nelfinavir is not required.

Rifabutin

Simultaneous use of azithromycin and rifabutin does not affect the concentration of each of the drugs in the blood serum. 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_Oh sildenafil or its main circulating metabolite.

Terfenadine

In pharmacokinetic studies, there was no 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 serum corresponded to those detected in other studies.

Special instructions:

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

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

The drug Ziromin should be used with caution in 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 urine, a tendency to bleeding, hepatic encephalopathy, therapy with Zyromin should be stopped and a study of the functional state of the liver. In case of impaired renal function: in patients with GFR 10-80 ml / min dose adjustment is not required, therapy with Zyromin should be performed with caution under the control of the state of kidney function.

As with the use of other antibacterial drugs, with Zyromin, patients should be regularly monitored for the presence of non-susceptible microorganisms and signs of development of superinfections, incl. fungal.

The drug Zyromin should not be used for longer courses than indicated in the instructions, becausepharmacokinetic 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 prolonged use of Zyromin, the development of pseudomembranous colitis caused by Clostridium difficile, both in the form of mild diarrhea, and severe colitis. With the development of antibiotic-associated diarrhea against the background of taking Zyromin, as well as within 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded. Drugs that inhibit the intestinal peristalsis are contraindicated.

When treating macrolides, incl. azithromycin, prolonged cardiac repolarization and interval QT, increasing the risk of developing cardiac arrhythmias, incl. polymorphic ventricular tachycardia of the "pirouette" type.

Care should be taken when using Zyromin in patients with proarrhythmogenic factors (especially in elderly patients),including with congenital or acquired lengthening of the interval QT; in patients taking antiarrhythmic drugs classes IA (quinidine, procainamide) or III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotics (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), in patients with disturbed water-electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, clinically significant bradycardia, cardiac arrhythmia, or severe heart failure.

The use of the drug Zyromin 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 that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated 500 mg.

Packaging:

For 3 tablets in a blister from AL / PVC / PVDC.

1 blister together with instructions for use are placed in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children!

Shelf life:

5 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004880

Date of registration:05.06.2018

Expiration Date:05.06.2023

The owner of the registration certificate:World Medical Ilach San ve Taj A.Sh.World Medical Ilach San ve Taj A.Sh. Turkey

Manufacturer: & nbsp

WORLD MEDICINE ILAC SAN. ve Tic. A.S. Turkey

Representation: & nbspTROKAS PHARMA LLCTROKAS PHARMA LLCRussia

Information update date: & nbsp21.06.2018

Illustrated instructions

Instructions

Zyromin (Ziromin)