Sumamed tablets 500mg, No. 3

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug:

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

• lower respiratory tract infections (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 (tablets), erysipelas, impetigo, secondarily infected dermatoses);

• the initial stage of Lyme disease (borreliosis) - erythema migrans (erythema migrans);

• urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis).

Film-coated tablets

Inside, without chewing, at least 1 hour before or 2 hours after meals, 1 time per day.

Adults and children over 12 years old weighing more than 45 kg

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

Acne vulgaris of moderate severity: 1 tab. (500 mg) 1 time per day for 3 days, then 1 table. (500 mg) once a week for 9 weeks; course dose - 6 g. The first weekly tablet should be taken 7 days after taking the first daily tablet (8th day from the start of treatment), the next 8 weekly tablets - with an interval of 7 days.

Lyme disease (the initial stage of borreliosis) - erythema migrans (erythema migrans): once a day for 5 days: on the 1st day - 1 g (2 tablets, 500 mg each), then from the 2nd to the 5th day - 1 table. (500 mg); course dose - 3 g.

Urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis): uncomplicated urethritis / cervicitis - 1 g (2 tablets, 500 mg each) once.

Children from 3 to 12 years old weighing less than 45 kg

Infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues: the drug is prescribed at the rate of 10 mg / kg 1 time per day for 3 days; course dose - 30 mg / kg. For ease of dosing, it is recommended to use the table below.

Calculation of the dose of SumamedЃ for children weighing less than 45 kg

Body weight, kg Dose of azithromycin tablets 125 mg

18-30 2 tab. (250 mg azithromycin)

31-44 3 tab. (375 mg azithromycin)

not less than 45 Use doses recommended for adults

In children under 3 years of age, it is recommended to use SumamedЃ, powder for oral suspension, 100 mg / 5 ml and SumamedЃ forte, powder for oral suspension, 200 mg / 5 ml.

For pharyngitis / tonsillitis caused by Streptococcus pyogenes, SumamedЃ is used at a dose of 20 mg / kg / day for 3 days; course dose 60 mg / kg. The maximum daily dose is 500 mg.

Lyme disease (the initial stage of borreliosis) - erythema migrans (erythema migrans): 20 mg / kg once a day on the 1st day, then at the rate of 10 mg / kg once a day from the 2nd to the 5th day ... For ease of use in children of a course dose of 60 mg / kg, it is recommended to take the drug SumamedЃ, powder for preparation of suspension for oral administration, 100 mg / 5 ml and SumamedЃ forte, powder for preparation of suspension for oral administration, 200 mg / 5 ml.

Special patient groups

Impaired renal function. When used in patients with mild to moderate renal impairment (Cl creatinine more than 40 ml / min), dose adjustment is not required.

Liver dysfunction. When used in patients with mild to moderate hepatic impairment, dose adjustment is not required.

Elderly patients.

No dose adjustment is required. Since the elderly may already have current proarrhythmogenic conditions, caution should be exercised when using SumamedЃ due to the high risk of developing cardiac arrhythmias, incl. arrhythmias of the 'pirouette' type.

Blue film-coated tablets, oval, biconvex, engraved with 'PLIVA' on one side and '500' on the other; at the break - from white to almost white.

1 tab.

azithromycin dihydrate 524.109 mg,?

which corresponds to the content of azithromycin 500 mg

Excipients: calcium hydrogen phosphate anhydrous - 93.891 mg, hypromellose - 6 mg, corn starch - 48 mg, pregelatinized starch - 40 mg, microcrystalline cellulose - 33.6 mg, sodium lauryl sulfate - 2.4 mg, magnesium stearate - 12 mg.

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

• severe hepatic impairment (Child-Pugh class C);

• severe liver dysfunction (film-coated tablets, 125 and 500 mg);

• severe renal impairment (Cl creatinine <40 ml / min);

• children under 3 (film-coated tablets, 125 mg) or 12 years with a body weight of up to 45 kg (capsules and film-coated tablets, 500 mg);

• simultaneous reception with ergotamine and dihydroergotamine.

With care: myasthenia gravis; mild to moderate liver dysfunction; mild to moderate renal impairment (Cl creatinine> 40 ml / min); the presence of proarrhythmogenic factors (especially in elderly patients): congenital or acquired prolongation of the QT interval, therapy with antiarrhythmic drugs of classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (antidepressants) ), fluoroquinolones (moxifloxacin and levofloxacin), imbalance in water and electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, clinically significant bradycardia, cardiac arrhythmia or severe heart failure; simultaneous use of digoxin, warfarin, cyclosporin.

pharmachologic effect

Bacteriostatic antibiotic of the macrolide-azalide group. Possesses a wide spectrum of antimicrobial action. The mechanism of action of azithromycin is associated with the suppression of protein synthesis of the microbial cell. By binding to the 50S-subunit of the ribosome, it inhibits peptide translocase at the stage of translation and suppresses protein synthesis, slowing down the growth and reproduction of bacteria. In high concentrations, it has a bactericidal effect.

Pharmacokinetics

Suction

After oral administration, azithromycin is well absorbed and rapidly distributed in the body. After a single dose of 500 mg, bioavailability is 37% due to the 'first pass' effect through the liver. Cmax in blood plasma is reached after 2-3 hours and is 0.4 mg / l.

Distribution

Protein binding is inversely proportional to plasma concentration and is 7-50%. The apparent Vd is 31.1 l / kg. 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 histohematogenous barriers and enters tissues. Concentration in tissues and cells is 10-50 times higher than in plasma, and in the focus of infection - 24-34% higher than in healthy tissues.

Metabolism

In the liver, it is demethylated, losing activity.

Withdrawal

T1 / 2 is very long - 35-50 hours. T1 / 2 of tissues is much larger. The therapeutic concentration of azithromycin lasts up to 5-7 days after taking the last dose. Azithromycin is excreted mainly unchanged - 50% through the intestines, 6% by the kidneys.

Side effect

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

Blood and lymphatic system disorders: infrequently - leukopenia, neutropenia, eosinophilia; very rarely - thrombocytopenia, hemolytic anemia.

From the side of metabolism: infrequently - anorexia.

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

From the nervous system: often - headache; infrequently - dizziness, impaired taste, paresthesia, drowsiness, insomnia, nervousness; rarely - agitation; unknown frequency - hypesthesia, anxiety, aggression, fainting, convulsions, psychomotor hyperactivity, loss of smell, perversion of smell, loss of taste, myasthenia gravis, delirium, hallucinations.

From the side of the organ of vision: infrequently - visual impairment.

On the part of the organ of hearing and labyrinth disorders: infrequently - hearing disorder, vertigo; unknown frequency - hearing impairment up to deafness and / or tinnitus.

From the side of the cardiovascular system: infrequently - a feeling of palpitations, flushing of the face; unknown frequency - decrease in blood pressure, increase in the QT interval on the ECG, arrhythmia of the 'pirouette' type, ventricular tachycardia.

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

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

From the liver and biliary tract: infrequently - hepatitis; rarely - liver dysfunction, cholestatic jaundice; unknown frequency - liver failure (in rare cases with a fatal outcome, mainly against the background of severe liver dysfunction), liver necrosis, fulminant hepatitis.

Skin and subcutaneous tissue disorders: infrequently - skin rash, itching, urticaria, dermatitis, dry skin, sweating; rarely - photosensitivity reaction; unknown frequency - Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.

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

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

On the part of the genitals and mammary gland: infrequently - metrorrhagia, dysfunction of the testicles.

Others: infrequently - asthenia, malaise, fatigue, facial edema, 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 - an increase in the activity of AST, ALT, an increase in the concentration of bilirubin in the blood plasma, an increase in the concentration of urea in the blood plasma, an increase in the concentration of creatinine in the blood plasma, a change in the content of potassium in the blood plasma, an increase in the activity of alkaline phosphatase in the blood plasma, an increase in the content 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, an increase in the concentration of bicarbonates in the blood plasma, a change in the sodium content in the blood plasma.

Application during pregnancy and lactation

During pregnancy and during breastfeeding, the use of the drug is possible only if the expected potential benefit of therapy to the mother outweighs the potential risk to the fetus and child.

If it is necessary to use the drug during lactation, breastfeeding should be suspended.

Application for violations of liver function

In severe liver dysfunction (class C on the Child-Pugh scale), the drug is contraindicated. With caution should be prescribed for mild to moderate liver dysfunction.

Application for impaired renal function

In severe renal impairment (CC <40 ml / min), the drug is contraindicated. The drug should be prescribed with caution for mild and moderate renal impairment.

Application in children

Contraindicated: children under 12 years of age and body weight less than 45 kg (for capsules and tablets 500 mg); children up to 3 years old (for tablets 125 mg; children up to 6 months old (for powder for suspension preparation).

Use in elderly patients

In elderly patients, dose adjustment of SumamedЃ is not required. Since this category of patients may have proarrhythmogenic conditions, SumamedЃ should be used with caution due to the high risk of developing arrhythmias, incl. ventricular arrhythmias of the 'pirouette' type.

special instructions

If one dose of the drug is missed, the missed dose should be taken as early as possible, and the subsequent ones should be taken at intervals of 24 hours.

SumamedЃ should be taken at least 1 hour before or 2 hours after taking antacids.

SumamedЃ should be used with caution in patients with mild and moderate hepatic impairment due to the possibility of developing fulminant hepatitis and severe liver failure. In the presence of symptoms of liver dysfunction, such as rapidly increasing asthenia, jaundice, dark urine, a tendency to bleeding, hepatic encephalopathy, therapy with SumamedЃ should be discontinued and a study of the functional state of the liver should be carried out.

In case of impaired renal function in patients with GFR 10-80 ml / min, dose adjustment is not required, therapy with SumamedЃ should be carried out with caution under the control of the state of renal function.

As with the use of other antibacterial drugs, during therapy with SumamedЃ, patients should be regularly examined for the presence of refractory microorganisms and signs of the development of superinfections, incl. fungal.

The drug SumamedЃ should not be used for longer courses than indicated in the instructions, because the pharmacokinetic properties of azithromycin make it possible 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 not recommended.

With prolonged use of SumamedЃ, the development of pseudomembranous colitis caused by Clostridium difficile is possible, both in the form of mild diarrhea and severe colitis. With the development of antibiotic-associated diarrhea while taking SumamedЃ, as well as 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded. Do not use drugs that inhibit intestinal motility.

When treating with macrolides, incl. azithromycin, lengthening of cardiac repolarization and QT interval was observed, increasing the risk of developing cardiac arrhythmias, incl. arrhythmias of the 'pirouette' type.

Caution should be exercised when using SumamedЃ in patients with the presence of proarrhythmogenic factors (especially in elderly patients), incl. with congenital or acquired lengthening of the QT interval; in patients
taking class IA antiarrhythmics (quinidine, procainamide), III (dofetilide, amiodarone, and sotalol), cisapride, terfenadine, antipsychotics (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), in patients with water disorders - electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, clinically significant bradycardia, cardiac arrhythmia or severe heart failure.

The use of SumamedЃ can provoke the development of myasthenic syndrome or exacerbate myasthenia gravis.

When used in patients with diabetes mellitus, as well as in patients following a low-calorie diet, it should be borne in mind that sucrose (0.32 XE / 5 ml) is included in the powder for preparing the SumamedЃ suspension as an auxiliary substance.

Influence on the ability to drive vehicles and mechanisms

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

Overdose

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

Treatment: symptomatic therapy.

Drug interactions

Antacids

Antacids do not affect the bioavailability of azithromycin, but reduce the Cmax in the blood by 30%, therefore SumamedЃ should be taken at least 1 hour before or 2 hours after taking these drugs and food.

Cetirizine

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

Didanosine (dideoxyinosine)

The simultaneous use of azithromycin (1200 mg / day) and didanosine (400 mg / day) in 6 HIV-infected patients did not reveal changes in the pharmacokinetic parameters of didanosine compared with the placebo group.

Digoxin (P-glycoprotein substrates)

ќдновременное применение макролидных антибиотиков, в т.ч. азитромицина, с субстратами –-гликопротеина, такими как дигоксин, приводит к повышению концентрации субстрата –-гликопротеина в сыворотке крови. “аким образом, при одновременном применении азитромицина и дигоксина необходимо учитывать возможность повышени¤ концентрации дигоксина в сыворотке крови.

«идовудин

ќдновременное применение азитромицина (однократный прием 1000 мг и многократный прием 1200 мг или 600 мг) оказывает незначительное вли¤ние на фармакокинетику, в т.ч. выведение почками зидовудина или его глюкуронидного метаболита. ќднако применение азитромицина вызывало увеличение концентрации фосфорилированного зидовудина, клинически активного метаболита в мононуклеарах периферической крови.  линическое значение этого факта не¤сно.

јзитромицин слабо взаимодействует с изоферментами системы цитохрома –450. Ќе вы¤влено, что азитромицин участвует в фармакокинетическом взаимодействии аналогичном эритромицину и другим макролидам. јзитромицин не ¤вл¤етс¤ ингибитором и индуктором изоферментов системы цитохрома –450.

јлкалоиды спорыньи

”читыва¤ теоретическую возможность возникновени¤ эрготизма, одновременное применение азитромицина с производными алкалоидов спорыньи не рекомендуетс¤.

Ѕыли проведены фармакокинетические исследовани¤ одновременного применени¤ азитромицина и препаратов, метаболизм которых происходит с участием изоферментов системы цитохрома –450.

јторвастатин

ќдновременное применение аторвастатина (10 мг ежедневно) и азитромицина (500 мг ежедневно) не вызывало изменени¤ концентраций аторвастатина в плазме крови (на основе анализа ингибировани¤ vћ - ој-редуктазы). ќднако в пострегистрационном периоде были получены отдельные сообщени¤ о случа¤х рабдомиолиза у пациентов, получающих одновременно азитромицин и статины.

 арбамазепин

¬ фармакокинетических исследовани¤х с участием здоровых добровольцев не вы¤влено существенного вли¤ни¤ на концентрацию карбамазепина и его активного метаболита в плазме крови у пациентов, получавших одновременно азитромицин.

?иметидин

¬ фармакокинетических исследовани¤х вли¤ни¤ циметидина при приеме в однократной дозе на фармакокинетику азитромицина не вы¤влено изменений фармакокинетики азитромицина, при условии применени¤ циметидина за 2 ч до азитромицина.

јнтикоагул¤нты непр¤мого действи¤ (производные кумарина)

¬ фармакокинетических исследовани¤х азитромицин не вли¤л на антикоагул¤нтный эффект варфарина при его приеме в однократной дозе 15 мг здоровыми добровольцами. —ообщалось о потенцировании антикоагул¤нтного эффекта после одновременного применени¤ азитромицина и антикоагул¤нтов непр¤мого действи¤ (производные кумарина). Ќесмотр¤ на то, что причинна¤ св¤зь не установлена, следует учитывать необходимость проведени¤ частого мониторинга протромбинового времени при применении азитромицина у пациентов, которые получают пероральные антикоагул¤нты непр¤мого действи¤ (производные кумарина).

?иклоспорин

¬ фармакокинетическом исследовании с участием здоровых добровольцев, которые в течение 3 дней принимали внутрь азитромицин (500 мг/сут однократно), а затем циклоспорин (10 мг/кг/сут однократно), было вы¤влено достоверное повышение Cmax в плазме крови и AUC0-5 циклоспорина. —ледует соблюдать осторожность при одновременном применении этих препаратов. ¬ случае необходимости одновременного применени¤ этих препаратов, следует проводить мониторинг концентрации циклоспорина в плазме крови и соответственно корректировать дозу.

Ёфавиренз

ќдновременное применение азитромицина (600 мг/сут однократно) и эфавиренза (400 мг/сут) ежедневно в течение 7 дней не вызывало какого-либо клинически значимого фармакокинетического взаимодействи¤.

‘луконазол

ќдновременное применение азитромицина (1200 мг однократно) не мен¤ло фармакокинетику флуконазола (800 мг однократно). ќбща¤ экспозици¤ и T1/2 азитромицина не измен¤лись при одновременном применении флуконазола, однако при этом наблюдали снижение Cmax азитромицина (на 18%), что не имело клинического значени¤.

»ндинавир

ќдновременное применение азитромицина (1200 мг однократно) не вызывало статистически достоверного вли¤ни¤ на фармакокинетику индинавира (по 800 мг 3 раза/сут в течение 5 дней).

ћетилпреднизолон

јзитромицин не оказывает существенного вли¤ни¤ на фармакокинетику метилпреднизолона.

Ќелфинавир

ќдновременное применение азитромицина (1200 мг) и нелфинавира (по 750 мг 3 раза/сут) вызывает повышение Css азитромицина в плазме крови.  линически значимых побочных эффектов не наблюдалось и коррекции дозы азитромицина при его одновременном применении с нелфинавиром не требуетс¤.

–ифабутин

ќдновременное применение азитромицина и рифабутина не вли¤ет на концентрацию каждого из препаратов в плазме крови. ѕри одновременном применении азитромицина и рифабутина иногда наблюдалась нейтропени¤. Ќесмотр¤ на то, что нейтропени¤ ассоциировалась с применением рифабутина, причинно-следственна¤ св¤зь между применением комбинации азитромицина и рифабутина и нейтропенией не установлена.

—илденафил

ѕри применении у здоровых добровольцев не получено доказательств вли¤ни¤ азитромицина (500 мг/сут ежедневно в течение 3 дней) на AUC и Cmax силденафила или его основного циркулирующего метаболита.

“ерфенадин

¬ фармакокинетических исследовани¤х не было получено доказательств взаимодействи¤ между азитромицином и терфенадином. —ообщалось о единичных случа¤х, когда возможность такого взаимодействи¤ нельз¤ было исключить полностью, однако не было ни одного конкретного доказательства, что такое взаимодействие имело место. Ѕыло установлено, что одновременное применение терфенадина и макролидов может вызвать аритмию и удлинение интервала QT.

“еофиллин

Ќе вы¤влено взаимодействие между азитромицином и теофиллином.

“риазолам/мидазолам

There were no significant changes in pharmacokinetic parameters with the simultaneous use of azithromycin with triazolam or midazolam in therapeutic doses.

Trimethoprim / Sulfamethoxazole

With the simultaneous use of trimethoprim / sulfamethoxazole with azithromycin, there was no significant effect on Cmax, total exposure or renal excretion of trimethoprim or sulfamethoxazole. Serum azithromycin concentrations were consistent with those found in other studies.