Sumamed suspension 20 ml. Suspension and tablets "Sumamed": complete instructions for use for children, antibiotic analogues. What do the numbers mean

Catad_pgroup Antibiotics macrolides and azalides

Sumamed - instructions for use

Trade name of the drug: SUMAMED®

International non-proprietary name : Azithromycin

Dosage form: capsules, coated tablets, powder for suspension for oral administration.

Reg:
P No. 015662/01 dated February 17, 2006
P No. 015662/02 of February 17, 2006
P No. 015662/03 dated 10.03.2006

Compound:

Capsules - hard, gelatinous, opaque, size No. 1. Case color - blue, cover - blue. Capsule contents: white to light yellow powder.
Tablets: blue tablets, round (125 mg) or oblong (500 mg) with biconvex surfaces and the designation "PLIVA" on one side and "125" or "500" on the other side. View in the fracture - from white to almost white.
Powder for suspension for oral administration 100 mg/5 ml - granulated powder of white or light yellow color with a characteristic smell of strawberries. After dissolution in water - a homogeneous suspension of white or light yellow color with a characteristic smell of strawberries.

Pharmacotherapeutic group : antibiotic, azalide ATC: J01FA10.

Pharmacological properties

Pharmacodynamics. It has a wide spectrum of antimicrobial activity. By binding to the 50S-sybunit of the ribosome, it inhibits the biosynthesis of proteins of the microorganism. In high concentrations, it has a bactericidal effect. Active against a number of gram-positive bacteria: Streptococcus pneumoniae, S. pyogenes, S. agalactiae, S. viridans, group C, F and G streptococci, Staphylococcus aureus, S. epidermidis. It has no effect on Gram-positive bacteria resistant to erythromycin. Effective against gram-negative microorganisms: Haemophilus influenzae, H. parainfluenzae and H. ducreyi, Moraxella catar-rhalis, Bordetella pertussis and B. parapertussis, Neisseria gonorrhoeae and N. meningitidis, Brucella melitensis, Helicobacter pylori, Gardnerella vaginalis.

Pharmacokinetics. When taken orally, SUMAMED is well absorbed and rapidly absorbed. distributed throughout the body. Penetrates into cells, including phagocytes, which migrate to the focus of inflammation, contributing to the creation of therapeutic concentrations of the drug at the site of infection. Already after 12-72 hours, high therapeutic concentrations (1-9 mg / kg) are created at the site of inflammation, exceeding the minimum inhibitory concentration for infectious agents. It has a long half-life and is slowly excreted from the tissues (average 60-76 hours). These properties determine the possibility of a single dose of the drug per day and a short dosing regimen (3 days), providing a 7-10-day course of treatment. It is metabolized mainly in the liver, metabolites are not active. The drug is excreted mainly with bile in unchanged form, a small part is excreted by the kidneys.

Indications for use

• Upper respiratory infections (bacterial pharyngitis/tonsillitis, sinusitis, otitis media);
• Infections of the lower respiratory tract (bacterial bronchitis, interstitial and alveolar pneumonia, exacerbation of chronic bronchitis);
• Infections of the skin and soft tissues (chronic erythema migrans - the initial stage of Lyme disease, erysipelas, impetigo, secondary pyodermatoses);
• Sexually transmitted infections (urethritis, cervicitis)
• Diseases of the stomach and duodenum associated with Helicobacter pylori.

• Hypersensitivity to macrolide antibiotics;
• Severe liver and kidney dysfunction

Dosage and administration

Inside, 1 time per day. Capsules and suspension are taken at least 1 hour before or 2 hours after meals. Bioavailability of tablets does not depend on food intake. Children from 6 months of age are recommended to use the drug in the form of an oral suspension or tablets of 125 mg.

For infections of the upper and lower respiratory tract, skin and soft tissues (with the exception of chronic erythema migrans)
Adults: 500 mg 1 time per day for 3 days (course dose 1.5 g) children: at the rate of 10 mg / kg of body weight 1 time per day for 3 days (course dose 30 mg / kg).

For chronic erythema migrans
Adults: 1 time per day for 5 days: 1st day - 1.0 g (2 tablets of 500 mg), then from the 2nd to 5th day - 500 mg each (course dose 3.0 g) children: on the 1st day - at a dose of 20 mg / kg of body weight and then from 2 to 5 days - daily at a dose of 10 mg / kg of body weight (course dose 30 mg / kg).

In diseases of the stomach and duodenum associated withHelicobacter pylori
1 g (2 tablets of 500 mg) per day for 3 days in combination with an antisecretory agent and other drugs.

Suspension preparation method
In a vial containing 17 g of powder, add 12 ml of distilled or boiled water. The volume of the resulting suspension is 23 ml. The shelf life of the prepared suspension is 5 days. Before use, the contents of the vial are thoroughly shaken until a homogeneous suspension is obtained. Immediately after taking the suspension, the child is allowed to drink a few sips of tea in order to rinse and swallow the remaining amount of the suspension in the mouth. After use, the syringe is disassembled and washed with running water, dried and stored in a dry place with the drug.

Side effects

Rare (in 1% of cases or less): From the gastrointestinal tract: melena, cholestatic jaundice, bloating, nausea, vomiting, diarrhea, constipation, loss of appetite, gastritis. Allergic reactions: skin rashes; photosensitivity, Quincke's edema. From the genitourinary system: vaginal candidiasis, nephritis. From the side of the cardiovascular system: palpitations, chest pain. From the side of the nervous system: dizziness, headache, vertigo, drowsiness, in children - headache (in the treatment of otitis media), hyperkinesia, anxiety, neurosis, sleep disturbances. Others: reversible moderate increase in liver enzymes, fatigue, itching, urticaria, conjunctivitis. In extremely rare cases neutrophilia and eosinophilia. Changed indicators return to the normal range 2-3 weeks after stopping treatment. The attending physician should be informed about the occurrence of any side effect.

Overdose

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

Interaction with other drugs

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

Release form

APPROVED

By order of the chairman

Committee of Pharmacy

Ministry of Health
Republic of Kazakhstan

From "______" __________ 201___

Instructions for medical use

medicinal product

Sumamed®

Tradename

Sumamed®

International non-proprietary name

Azithromycin

Dosage form

Powder for suspension for oral administration, 100mg/5ml.

Compound

One vial contains

active substance - azithromycin (in the form of azithromycin dihydrate) - 0.500 g (0.5241 g).

Excipients: sucrose, sodium phosphate anhydrous, hydroxypropycellulose, xanthan gum, cherry flavors, banana flavor, vanilla flavor, anhydrous colloidal silicon.

Description

Granular powder from white to light yellow color with a characteristic smell of banana and cherry.

The prepared solution is a homogeneous suspension of white or light yellow color with a characteristic smell of banana and cherry.

Pharmacotherapeutic group

Antimicrobials for systemic use.

Antibacterial drugs for systemic use. Macrolides, lincosamides and streptogramins. Macrolides. Azithromycin.

ATX code J01FA10

Pharmacological properties

Pharmacokinetics

Suction

Bioavailability after oral administration is about 37%. The maximum concentration in blood serum is reached 2-3 hours after taking the drug.

Distribution

When taken orally, azithromycin is distributed throughout the body. In pharmacokinetic studies, it was found that the concentration of azithromycin in tissues is significantly higher (50 times) than in blood plasma, which indicates a pronounced binding of the drug to tissues.

Serum protein binding varies with plasma concentrations and ranges from 12% at 0.5 µg/mL to 52% at 0.05 µg/mL in plasma. The volume of distribution at steady state was 31.1 l/kg.

breeding

The final half-life from blood plasma fully reflects the half-life from tissues for 2-4 days.

Approximately 12% of an IV dose of azithromycin is excreted unchanged in the urine over the next 3 days. A particularly high concentration of unchanged azithromycin was found in human bile. Also, 10 metabolites were identified in bile, which were formed by N- and O-demethylation, hydroxylation of deosamine and aglycone rings, and cleavage of the cladinose conjugate. Comparison of the results of liquid chromatography and microbiological analyzes showed that azithromycin metabolites are not microbiologically active.

In animal tests, high concentrations of azithromycin have been found in phagocytes. This also establishes the fact that during active phagocytosis, higher concentrations of azithromycin are released than during a decrease in the activity and intensity of phagocytosis. Therefore, in animal studies, high concentrations of azithromycin have been identified in inflammatory foci.

Pharmacodynamics

Mechanism of action:

Sumamed is a broad-spectrum antibiotic, a representative of a subgroup of macrolide antibiotics - azalides. The molecule is built by adding a nitrogen atom to the lactone ring of erythromycin A. The chemical name of azithromycin is 9-deoxy-9a-aza-9a-methyl 9a-homoerythromycin A.

Molecular weight: 749.0.

The mechanism of action of azithromycin is to inhibit bacterial protein synthesis by binding to the 50S subunit of ribosomes and preventing peptide translocation without affecting polynucleotide synthesis.

Resistance mechanism:

Resistance to azithromycin may be congenital or acquired. There are three main mechanisms of resistance in microorganisms: changes in the target strain, changes in antibiotic transport, and modifications of antibiotics.

Complete cross-resistance exists in Streptococcus pneumoniae, group A β-hemolytic streptococcus, Enterococcus faecalis, and Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA) to erythromycin, azithromycin, other macrolides, and lincosamides.

The antimicrobial spectrum of azithromycin includes various gram-positive and gram-negative microorganisms, anaerobic microorganisms and intracellular and clinically atypical pathogens.

*Sensitive to erythromycin

Sensitivity

The prevalence of acquired resistance may vary geographically and over time for different organisms. It is desirable to collect information from local sources on resistance, especially in the treatment of severe infections. If necessary, a specialist in the field should be consulted to determine the level of resistance in the area. the benefit of treating certain types of infections with this drug is questionable.

GENERALLY SENSITIVE MICROORGANISMS

Staphylococcus aureus

methicillin sensitive

Streptococcus pneumoniae

penicillin sensitive

Streptococcus pyogenes (gr. A)

Aerobic gram-negative bacteria

haemophilus influenzae

haemophilus parainfluenzae

Legionella pneumophila

Moraxella catarrhalis

Pasteurella multocida

anaerobic bacteria

Clostridium perfringens

Fusobacterium spp.

Prevotella spp.

Porphyromonas spp.

Other bacteria

Chlamydia trachomatis

SPECIES THAT BECOME RESISTANT IN SELECTED CASES

Aerobic gram-positive bacteria

Streptococcus pneumoniae

With intermediate sensitivity to penicillin

penicillin resistant

INGENITAL RESISTANCE

Aerobic gram-positive bacteria

Enterococcus faecalis

Staphylococci MRSA, MRSE (methicillin-resistant Staphylococcus aureus)*

anaerobic bacteria

Bacteroides fragilis group of bacteroids

* Methicillin-resistant Staphylococcus aureus has a very high degree of acquired resistance to macrolides and was placed on this list because it is rarely susceptible to azithromycin.

Indications for use

Respiratory infections, including pharyngitis/tonsillitis, sinusitis, otitis media

Lower respiratory infections, including bacterial bronchitis, community-acquired pneumonia

Skin and soft tissue infections: erythema migrans (early Lyme disease), erysipelas, impetigo, secondary pyodermatoses

Infections of the stomach and duodenum caused by Helicobacter pylori

Method of application and dose

Sumamed® in the form of an oral suspension is taken 1 time per day 1 hour before or 2 hours after a meal. The dose of the drug must be measured using a dosing syringe or a measuring spoon that is attached to the drug (with a child weighing up to 15 kg, a dosing syringe should be used; with a weight of more than 15 kg - a measuring spoon).

In the treatment of infections of the upper and lower respiratory tract, skin and soft tissues (except for migrating erythema), the total dose of Sumamed is 30 mg / kg, which must be taken for 3 days (10 mg / kg 1 time per day):

For children, the drug is prescribed based on weight:

Azithromycin has been shown to be effective in the treatment of streptococcal pharyngitis in children as a single dose of 10 mg/kg or 20 mg/kg for 3 days.

For the prevention of pharyngitis caused by Streptococcus pyogenes with possible rheumatic fever, penicillin is used as a concomitant disease.

Chronic erythema migrans

In the treatment of gastric ulcers and duodenal infections caused by Helicobacter pylori, a dose of 20 mg / kg per day is used in combination with antisecretory agents and other drugs of the doctor's choice.

Renal failure.

In patients with mild renal dysfunction (GFR 10-80 ml/min) there is no need to change the dose. Patients with severely impaired renal function (GFR<10 мл/мин) необходимо с осторожностью применять азитромицин.

Liver failure.

Since azithromycin is metabolized in the liver and excreted in the bile, the drug should not be used in patients with severe liver disease. Studies aimed at studying the effect of azithromycin on liver function have not been conducted.

Elderly patients

Elderly patients are prescribed the same dose as adults. Among elderly patients, proarrhythmic conditions are possible, so the drug is used with caution due to the risk of developing cardiac arrhythmia and ventricular tachycardia of the "pirouette" type.

Suspension preparation method

To prepare 20 ml of suspension, it is necessary to add 12 ml of water at room temperature (not hot!) to a vial containing 400 mg of azithromycin using a dosing syringe.

Before use, the contents of the vial are thoroughly shaken until a homogeneous suspension is obtained. Immediately after taking the suspension, the child is allowed to drink a few sips of liquid in order to rinse and swallow the remaining amount of the suspension in the mouth.

Side effects

The list below lists adverse reactions identified in clinical trials and post-marketing experience, by system organ class and frequency.

The frequency of adverse reactions is ranked as follows: very often (≥ 1/10), often (≥ 1/100 to<1/10), нечасто (≥ 1/1, 000 до <1/100), редко (≥ 1/10, 000 до <1/1, 000), очень редко (<1/10, 000), неизвестно (невозможно оценить на основе имеющихся данных). В каждой группе частоты, нежелательные эффекты представлены в порядке убывания серьезности.

Adverse reactions associated with the complex for the prevention and treatment of Mycobacterium Avium are possible or likely, based on clinical studies and post-marketing experience. These adverse reactions differ in type or frequency from those reported for immediate release or extended release formulations:

Contraindications

Hypersensitivity to azithromycin, erythromycin, other macrolide and ketolide antibiotics, or other components of the drug

Severe liver and kidney dysfunction

lactation period

Drug Interactions

Antacids: When studying the effect of the simultaneous use of antacids on the pharmacokinetics of azithromycin, no changes in bioavailability were noted, although the maximum plasma concentration of azithromycin decreased by 25%. Patients should not take azithromycin and antacids at the same time. Cetirizine: In healthy volunteers, co-administration of a 5-day course of azithromycin with cetirizine 20 mg at steady state did not result in a pharmacokinetic interaction and a significant change in the QT interval.

Didanosine (dideoxyinosine): Co-administration of azithromycin 1200 mg/day with didanosine 400 mg/day in 6 HIV-positive patients did not affect the steady-state pharmacokinetics of didanosine compared to placebo.

Digoxin (P-gp substrates): Co-administration of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates such as digoxin results in increased serum levels of P-glycoprotein substrates. Therefore, with the simultaneous use of azithromycin and P-glycoprotein substrates, such as digoxin, the possibility of increasing the concentration of P-glycoprotein substrates in serum should be borne in mind.

Zidovudine: With a single dose of 1000 mg and repeated use of 1200 mg or 600 mg of azithromycin, there was a slight effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolites. However, azithromycin administration increased the concentration of phosphorylated zidovudine (a clinically active metabolite) in peripheral blood mononuclear cells. The clinical significance of these indicators remains uncertain, but they may be useful to patients.

Azithromycin does not interact with the liver cytochrome P450 system. It does not participate in pharmacokinetic drug interactions like erythromycin and other macrolides. Azithromycin does not induce or inactivate cytochrome P450 via the cytochrome-metabolite complex.

Ergot derivatives: Due to the theoretical possibility of developing ergotism, the simultaneous use of azithromycin with ergot derivatives is not recommended. Pharmacokinetic studies have been performed with azithromycin and the following drugs with known cytochrome P450-mediated metabolism.

Atorvastatin: Co-administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter plasma concentrations of atorvastatin (based on HMG CoA reductase analysis). However, post-marketing cases of rhabdomyolysis have been reported in patients receiving azithromycin with statins.

Carbamazepine: In a pharmacokinetic interaction study of azithromycin in healthy volunteers, the drug did not significantly affect plasma levels of carbamazepine or its active metabolites.

Cimetidine: No change in the pharmacokinetics of azithromycin was noted in a pharmacokinetic study investigating the effect of a single dose of cimetidine taken 2 hours before azithromycin on the pharmacokinetics of azithromycin.

Coumarin oral anticoagulants: In pharmacokinetic interaction studies, azithromycin did not alter the anticoagulant effect of a single 15 mg dose of warfarin administered to healthy volunteers. In the post-marketing period, there have been reports of increased anticoagulation after co-administration of azithromycin and oral coumarin anticoagulants. Although a causal relationship has not been established, the frequency of monitoring of prothrombin time should be considered when prescribing azithromycin to patients receiving oral anticoagulants such as coumarin.

Cyclosporine: In a pharmacokinetic study in healthy volunteers who received 500 mg/day of azithromycin orally for 3 days followed by a single oral dose of 10 mg/kg of cyclosporine, Cmax and AUC0-5 of cyclosporine were found to be significantly elevated. Therefore, caution should be exercised before concurrent administration of these drugs is considered. If co-administration of these drugs is necessary, ciclosporin levels should be monitored and the dose adjusted accordingly.

Efavirenz: Co-administration of a single dose of azithromycin 600 mg and efavirenz 400 mg daily for 7 days did not result in clinically significant pharmacokinetic interactions.

Fluconazole: Co-administration of a single dose of 1200 mg of azithromycin does not alter the pharmacokinetics of a single dose of 800 mg of fluconazole. The total exposure and half-life of azithromycin did not change when co-administered with fluconazole, however, there was a clinically insignificant decrease in Cmax (18%) of azithromycin.

Indinavir: Co-administration of a single dose of 1200 mg of azithromycin had no statistically significant effect on the pharmacokinetics of indinavir administered at a dose of 800 mg three times a day for 5 days.

Methylprednisolone: ​​In a pharmacokinetic interaction study in healthy volunteers, azithromycin did not show a significant effect on the pharmacokinetics of methylprednisolone.

Midazolam: In healthy volunteers, co-administration with azithromycin 500 mg/day for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of a single dose of midazolam 15 mg.

Nelfinavir: Co-administration of azithromycin (1200 mg) and steady-state nelfinavir (750 mg three times daily) resulted in an increase in azithromycin concentrations. No clinically significant side effects were observed and dose adjustment is not required.

Rifabutin: The simultaneous use of azithromycin and rifabutin did not affect the concentration of these drugs in the blood plasma.

Neutropenia was detected with the simultaneous use of azithromycin and rifabutin. Although neutropenia has been associated with the use of rifabutin, a causal relationship with concomitant use of azithromycin has not been established.

Sildenafil: In normal healthy male volunteers, there is no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC and Cmax of sildenafil or its major circulating metabolite.

Terfenadine: No interactions between azithromycin and terfenadine have been reported in pharmacokinetic studies. In some cases, it is not possible to completely eliminate the possibility of an interaction. However, there was no concrete evidence that such an interaction took place.

Theophylline: There is no evidence of a clinically significant pharmacokinetic interaction between azithromycin and theophylline when administered concomitantly to healthy volunteers.

Triazolam: In 14 healthy volunteers, co-administration of azithromycin 500 mg on day 1 and 250 mg on day 2 with triazolam 0.125 mg on day 2 had no significant effect on any of the pharmacokinetic variables for triazolam compared with co-administration of triazolam and placebo.

Trimethoprim/sulfamethoxazole: Co-administration of trimethoprim/sulfamethoxazole DS (160 mg/800 mg) for 7 days with azithromycin 1200 mg on day 7 had no significant effect on peak concentration, total exposure, or elimination of trimethoprim or sulfamethoxazole. Serum azithromycin concentrations were similar to those observed in other studies.

special instructions

As with erythromycin and other macrolides, rare serious allergic reactions have been reported, including angioedema and anaphylaxis (rarely fatal). Some of these reactions to azithromycin lead to the development of recurrent symptoms and require a longer period of observation and treatment.

The liver is the main organ for the elimination of azithromycin, so azithromycin should be used with caution in patients with severe liver disease. Cases of fulminant hepatitis potentially leading to life-threatening liver failure have been reported.

Some patients may have had existing medical conditions

Liver or they have taken other hepatotoxic drugs.

If signs and symptoms of liver dysfunction occur, such as rapidly developing asthenia associated with jaundice, dark urine, bleeding tendency, or hepatic encephalopathy, perform liver function tests/tests immediately.

With the development of liver dysfunction, stop taking azithromycin.

In patients receiving ergot derivatives, the appearance of ergotism is provoked by the simultaneous administration of certain macrolide antibiotics. There are no data on the possibility of an interaction between ergot and azithromycin. However, due to the theoretical possibility of ergotism, azithromycin and ergot derivatives are taken separately.

Diarrhea caused by Clostridium difficile (CDAD) has been reported in all cases of use of antibacterial agents, including azithromycin, and can range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal intestinal flora, leading to overgrowth of C. difficile.

C. difficile produces toxins A and B, which contribute to the development of CDAD. The hypertoxin-producing strain of C. difficile results in increased morbidity and mortality, as these infections may be resistant to antimicrobial therapy and may require treatment.

Colectomy. CDAD should be considered in all patients who complain of diarrhea after antibiotic use. A careful history is essential, as CDAD may develop up to two months after administration of antibacterial agents.

In patients with severe renal insufficiency (GFR<10 мл / мин) наблюдалось 33% увеличение системного воздействия азитромицина.

Prolonged cardiac repolarization and prolongation of the QT interval, leading to the risk of developing cardiac arrhythmias and torsades de pointes, have been reported with other macrolides, including azithromycin. The following conditions increase the risk of ventricular arrhythmias (including torsades de pointes) that can lead to cardiac arrest, so azithromycin should be used with caution in patients with current proarrhythmic conditions (especially women and elderly patients), for example:

With congenital or documented QT prolongation

Who are currently being treated with other active substances known to prolong the QT interval, such as class IA antiarrhythmics (quinidine and procainamide) and class III antiarrhythmics (dofetilide, amiodarone and sotalol), cisapride and terfenadine; antipsychotics such as pimozide; antidepressants such as citalopram; and fluoroquinolones such as moxifloxacin and levofloxacin

With electrolyte imbalance, especially in cases of hypokalemia and hypomagnesemia

With clinically significant bradycardia, cardiac arrhythmias, or severe heart failure.

Exacerbation of myasthenia symptoms and new onset of myasthenia gravis have been reported in patients receiving azithromycin.

Penicillin is generally the drug of choice in the treatment of laryngitis/tonsillitis caused by Streptococcus pyogenes and is used as a prophylaxis in acute rheumatic fever. Azithromycin is generally effective against streptococcal pharyngitis, but there is no information regarding its effectiveness in preventing acute rheumatic fever.

The safety and efficacy of intravenous azithromycin for the treatment of infections in children have not been established.

The safety and efficacy of Mycobacterium Avium Complex for prophylaxis or treatment in children have not been established.

Sucrose.

The drug contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption syndrome or sucrase-isomaltase insufficiency should not take this medicine.

Pregnancy

The use of the drug during pregnancy is possible only if the expected benefit outweighs the potential risk to the fetus.

5 ml of the finished product contains azithromycin 100 mg

Release form

Powder for the preparation of a suspension for oral administration in a vial complete with a measuring spoon and / or syringe for dosing in a cardboard pack

pharmachologic effect

Bacteriostatic antibiotic of the macrolide-azalide group. It has a wide spectrum of antimicrobial activity.

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 an antibiotic or may acquire resistance to it.

In most cases, Sumamed is active against aerobic gram-positive bacteria: Staphylococcus aureus (methicillin-sensitive strains), Streptococcus pneumoniae (penicillin-sensitive strains), Streptococcus pyogenes; aerobic gram-negative bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis, Pasteurella multocida, Neisseria gonorrhoeae; anaerobic bacteria: Clostridium perfringens, Fusobacterium spp., Prevotella spp., Porphyromonas spp.; 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 show a very high degree of resistance to macrolides); gram-positive bacteria resistant to erythromycin; anaerobes - Bacteroides fragilis.

Indication for use

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);
• infections of the lower respiratory tract (acute bronchitis, exacerbation of chronic bronchitis, pneumonia, including those caused by atypical pathogens);
• skin and soft tissue infections (erysipelas, impetigo, secondarily infected dermatoses, moderate acne vulgaris (for tablets));
• the initial stage of Lyme disease (borreliosis) - migratory erythema (erythema migrans);
• urinary tract infections (urethritis, cervicitis) caused by Chlamydia trachomatis (for tablets and capsules).

Dosage and administration

Assign to children aged 6 months to 3 years.

The suspension is administered orally 1 time / day, 1 hour before or 2 hours after a meal. After taking the drug Sumamed, the child must be offered to drink a few sips of water so that he can swallow the rest of the suspension.

Before each dose of the drug, the contents of the vial are thoroughly shaken until a homogeneous suspension is obtained. If the required volume of the suspension has not been taken from the vial within 20 minutes after shaking, the suspension should be shaken again, the required volume should be taken and given to the child.

The dosage and duration of treatment is selected by the doctor depending on the disease, as well as the age and weight of the patient.

Suspension preparation and storage method: 12 ml of water is added to the contents of the vial intended for the preparation of 20 ml of suspension (nominal volume) using a dosing syringe and shaken until a homogeneous suspension is obtained. The volume of the resulting suspension will be about 25 ml, which exceeds the nominal volume by about 5 ml. This is provided to compensate for the inevitable losses of the suspension when dosing the drug. The prepared suspension can be stored at a temperature not exceeding 25°C for no more than 5 days.

Contraindications

• severe liver dysfunction;
• severe renal impairment (CK< 40 мл/мин);
• simultaneous reception with ergotamine and dihydroergotamine;
• children's age up to 6 months;
• sucrase/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption
• hypersensitivity to azithromycin, erythromycin, other macrolides or ketolides, or other components of the drug.

special instructions

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

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

The drug Sumamed should not be used for longer courses than indicated in the instructions, because. The pharmacokinetic properties of azithromycin allow a short and simple dosing regimen to be recommended.

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

If necessary, the use of the drug during lactation, breastfeeding should be suspended.

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C. The prepared suspension can be stored at a temperature not exceeding 25°C for 5 days.

INN: Azithromycin

Manufacturer: Pliva Hrvatska d.o.o.

Anatomical-therapeutic-chemical classification: Azithromycin

Registration number in the Republic of Kazakhstan: No. RK-LS-5 No. 003550

Registration period: 10.06.2016 - 10.06.2021

Instruction

Tradename

Sumamed ®

International non-proprietary name

Azithromycin

Dosage form

Powder for suspension for oral administration, 100mg/5ml.

Compound

One vial contains

active substance- azithromycin (in the form of azithromycin dihydrate) - 0.500 g (0.5241 g).

Excipients: sucrose, sodium phosphate anhydrous, hydroxypropycellulose, xanthan gum, cherry flavors, banana flavor, vanilla flavor, anhydrous colloidal silicon.

Description

Granular powder from white to light yellow color with a characteristic smell of banana and cherry.

The prepared solution is a homogeneous suspension of white or light yellow color with a characteristic smell of banana and cherry.

Pharmacotherapeutic group

Antibacterial drugs for systemic use. Macrolides, lincosamides and streptogramins. Macrolides. Azithromycin.

ATX code J01FA10

Pharmacological properties

Pharmacokinetics

Azithromycin is rapidly absorbed when taken orally, due to its stability in an acidic environment and lipophilicity. After a single oral dose, 37% of azithromycin is absorbed, and the peak plasma concentration (0.41 µg / ml) is recorded after 2-3 hours. Vd is approximately 31 l/kg. Azithromycin penetrates well into the respiratory tract, organs and tissues of the urogenital tract, the prostate gland, into the skin and soft tissues, reaching from 1 to 9 µg / ml, depending on the type of tissue. The high tissue concentration (50 times higher than the plasma concentration) and long half-life are due to the low binding of azithromycin to plasma proteins, as well as its ability to penetrate eukaryotic cells and concentrate in the low pH environment surrounding lysosomes. The ability of azithromycin to accumulate in lysosomes is especially important for the elimination of intracellular pathogens. Phagocytes deliver azithromycin to the sites of infection, where it is released during phagocytosis. But despite the high concentration in phagocytes, azithromycin does not affect their function. Therapeutic concentration remains 5-7 days after ingestion of the last dose. When taking azithromycin, a transient increase in the activity of liver enzymes is possible. Removal of half the dose from plasma is reflected in a decrease in half the dose in tissues within 2-4 days. After taking the drug in the range from 8 to 24 hours, the half-life is 14-20 hours, and after taking the drug in the range from 24 to 72 hours - 41 hours, which allows you to take Sumamed 1 time per day. The main route of excretion is with bile. Approximately 50% is excreted unchanged, the other 50% is in the form of 10 inactive metabolites. Approximately 6% of the dose taken is excreted by the kidneys.

Pharmacodynamics

Sumamed ® is a broad-spectrum antibiotic, the first representative of a new subgroup of macrolide antibiotics - azalides. It has a bacteriostatic effect, but when high concentrations are created in the focus of inflammation, it causes a bactericidal effect. Binding 50S ribosomal subunit, Sumamed ® inhibits protein synthesis in sensitive microorganisms, showing activity against most strains of gram-positive, gram-negative, anaerobic, intracellular and other microorganisms.

MIC90 ≤ 0.01 µg/mL

Mycoplasma pneumoniae Haemophilus ducreyi

MIC90 0.01 - 0.1 µg/ml

Moraxella catarrhalis Propionibacterium acnes

Gardnerella vaginalis Actinomyces species

Bordetella pertussis Borrelia burgdorferi

Mobiluncus species

MIC900.1 - 2.0 µg/ml

Haemophilus influenzae Streptococcus pyogenes

Haemophilus parainfluenzae Streptococcus pneumoniae

Legionella pneumophila Streptococcus agalactiae

Neisseria meningitidis Streptococcus viridans

Neisseria gonorrhoeae Streptococcus group C, F, G

Helicobacter pylori Peptococcus sp.

Campylobacter jejuni Peptostreptococcus

Pasteurella multocida Fusobacterium necrophorum

Pasteurella haemolytica Clostridium perfringens

Brucella melitensis Bacteroides bivius

Bordetella parapertussis Chlamydia trachomatis

Vibrio cholerae Chlamydia pneumoniae

Vibrio parahaemolyticus Ureaplasma urealyticum

Plesiomonas shigelloides Listeria monocytogenes

Staphylococcus epidermidis

Staphylococcus aureus*

(*erythromycin - sensitive strain)

MIC902.0 - 8.0 µg/ml

Escherichia coli Bacteroides fragilis

Salmonella enteritidis Bacteroides oralis

Salmonella typhi Clostridium difficile

Shigella sonnei Eubacterium lentum

Yersinia enterocolitica Fusobacterium nucleatum

Acinetobacter calcoaceticus Aeromonas hydrophilia

Indications for use

Respiratory infections, including pharyngitis/tonsillitis, sinusitis, otitis media

Lower respiratory infections, including acute exacerbation of chronic bronchitis, community acquired pneumonia

Skin and soft tissue infections: erythema migrans (early Lyme disease), erysipelas, impetigo, secondary pyodermatoses

Infections of the stomach and duodenum caused by Helicobacter pylori

Method of application and dose

Sumamed ® in the form of an oral suspension, take 1 time per day 1 hour before or 2 hours after a meal. The dose of the drug must be measured using a dosing syringe or a measuring spoon that is attached to the drug (with a weight of up to 15 kg, a dosing syringe should be used; with a weight of more than 15 kg - a measuring spoon).

In the treatment of infections of the upper and lower respiratory tract, skin and soft tissues (except for erythema migrans) the total dose of Sumamed is 30 mg / kg, which must be taken for 3 days (10 mg / kg 1 time per day).:

For children, the drug is prescribed based on weight:

Azithromycin has been shown to be effective in the treatment of streptococcal pharyngitis in children as a single dose of 10 mg/kg or 20 mg/kg for 3 days.

For the prevention of pharyngitis caused by Streptococcus pyogenes with possible rheumatic fever, penicillin is used as a concomitant disease.

Chronic erythema migrans

The heading dose of the drug is 60 mg / kg: once at 20 mg / kg - on the 1st day and 10 mg / kg - in the next, from 2 to 5 days.

In the treatment of stomach ulcers and duodenal infections caused by Helicobacter pylori use a dose of 20 mg / kg per day in combination with antisecretory agents and other drugs at the discretion of the physician.

Renal failure.

In patients with mild renal dysfunction (GFR 10-80 ml/min) there is no need to change the dose. Patients with severely impaired renal function (GFR<10 мл/мин) необходимо с осторожностью применять азитромицин.

Liver failure.

Since azithromycin is metabolized in the liver and excreted in the bile, the drug should not be used in patients with severe liver disease. Studies aimed at studying the effect of azithromycin on liver function have not been conducted.

Elderly patients

Elderly patients are prescribed the same dose as adults. Among elderly patients, proarrhythmogenic conditions are possible, so the drug is used with caution due to the risk of developing cardiac arrhythmia and bidirectional tachycardia.

Suspension preparation method

To prepare 20 ml of suspension, it is necessary to add 12 ml of water to a vial containing 400 mg of azithromycin using a dosing syringe.

Before use, the contents of the vial are thoroughly shaken until a homogeneous suspension is obtained. Immediately after taking the suspension, the child is allowed to drink a few sips of liquid in order to rinse and swallow the remaining amount of the suspension in the mouth.

Side effects

Often

Headache

Nausea, vomiting, diarrhea, abdominal pain

Decrease in white blood cells, increase in eosinophils, decrease in blood bicarbonate, increase in basophils, increase in monocytes, increase in neutrophils

Infrequently

Constipation, flatulence, dyspepsia, gastritis, dysphagia, bloating,

dry mouth, belching, mouth ulcers, hypersecretion of salivary glands

Dizziness, drowsiness, taste perversion, paresthesia

Hearing impairment, dizziness

Cardiopalmus

Shortness of breath, nosebleeds

visual impairment

Anorexia

Osteoarthritis, myalgia, back pain, neck pain

Nervousness, insomnia

Leukopenia, neutropenia, eosinophilia

Candidiasis, vaginal infections, pneumonia, fungal infections, bacterial infection, pharyngitis, gastroenteritis, respiratory disorders, rhinitis, candidiasis

tides

Rash, pruritus, urticaria, dermatitis, dry skin, hyperhidrosis

Angioedema, hypersensitivity

Dysuria, kidney pain

Metrorrhagia, testicular involvement

Edema, asthenia, malaise, fatigue, facial edema, chest pain, fever, pain, peripheral edema

Increase in aspartate aminotransferase, increase in alanine

aminotransferase, increased bilirubin in the blood, increased urea in

blood, increased blood creatinine, abnormal blood potassium, increased blood alkaline phosphatase, increased chloride, increased glucose, increased platelets, decreased hematocrit, increased bicarbonate, abnormal sodium

Rarely

Agitation

Abnormal liver function, cholestatic jaundice

photosensitivity reactions

unknown

Pseudomembranous colitis

Thrombocytopenia, hemolytic anemia

Anaphylactic reaction

Aggression, anxiety, delusions, hallucinations

Syncope, convulsions, paresthesia, psychomotor hyperactivity, anosmia, ageusia, parosomia, myasthenia gravis

Hearing impairment, including deafness and/or tinnitus

Bidirectional tachycardia and arrhythmias including ventricular tachycardia, QT prolongation on ECG

hypotension

- pancreatitis, tongue discoloration

Liver failure (rarely fatal) fulminant hepatitis, liver necrosis

Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme

Arthralgia

Acute renal failure, interstitial nephritis

Adverse reactions associated with the prevention and treatment of infections caused by the complex Mycobacterium Avium possible or probable based on clinical studies and post-marketing experience. These adverse reactions differ in type or frequency from those reported for immediate release or extended release formulations:

Contraindications

Hypersensitivity to macrolide antibiotics

Severe liver and kidney dysfunction

lactation period

Medicinal interactions

Antacids: When studying the effect of the simultaneous use of antacids on the pharmacokinetics of azithromycin, no changes in bioavailability were noted, although the maximum concentration of azithromycin in the blood plasma decreased by 25%. Patients should not take azithromycin and antacids at the same time. Cetirizine: In healthy volunteers, co-administration of a 5-day course of azithromycin with cetirizine 20 mg at steady state did not lead to a pharmacokinetic interaction and a significant change in the QT interval.

Didanosine (dideoxyinosine): Co-administration of azithromycin 1200 mg/day with didanosine 400 mg/day in 6 HIV-positive patients did not affect the steady-state pharmacokinetics of didanosine compared with placebo.

Digoxin (substratesP- gp): Co-administration of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates such as digoxin results in increased serum levels of P-glycoprotein substrates. Therefore, with the simultaneous use of azithromycin and P-glycoprotein substrates, such as digoxin, the possibility of increasing the concentration of P-glycoprotein substrates in serum should be borne in mind.

Zidovudine: With a single application of 1000 mg and repeated use of 1200 mg or 600 mg of azithromycin, there was a slight effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolites. However, azithromycin increased the concentration of phosphorylated zidovudine (a clinically active metabolite) in peripheral blood mononuclear cells. . Clinical significance remains uncertain these indicators, but they may be useful to patients.

Azithromycin does not interact with the liver cytochrome P450 system. It does not participate in pharmacokinetic drug interactions like erythromycin and other macrolides. Azithromycin does not induce or inactivate cytochrome P450 via the cytochrome-metabolite complex.

Ergotamine derivatives: Due to the theoretical possibility of developing ergotism, the simultaneous use of azithromycin with ergot derivatives is not recommended. Pharmacokinetic studies have been performed with azithromycin and the following drugs with known cytochrome P450-mediated metabolism.

Atorvastatin: Co-administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter plasma concentrations of atorvastatin (based on HMG CoA reductase analysis). However, post-marketing cases of rhabdomyolysis have been reported in patients receiving azithromycin with statins.

Carbamazepine: In a pharmacokinetic interaction study of azithromycin in healthy volunteers, the drug did not significantly affect plasma levels of carbamazepine or its active metabolites.

Cimetidine: No change in the pharmacokinetics of azithromycin was noted in a pharmacokinetic study investigating the effect of a single dose of cimetidine taken 2 hours before azithromycin on the pharmacokinetics of azithromycin.

Coumarin oral anticoagulants: In pharmacokinetic interaction studies, azithromycin did not alter the anticoagulant effect of a single 15 mg dose of warfarin administered to healthy volunteers. In the post-marketing period, there have been reports of increased anticoagulation after co-administration of azithromycin and oral coumarin anticoagulants. Although a causal relationship has not been established, the frequency of monitoring of prothrombin time should be considered when prescribing azithromycin to patients receiving oral anticoagulants such as coumarin.

Cyclosporine: In a pharmacokinetic study in healthy volunteers who received 500 mg/day of azithromycin orally for 3 days followed by a single oral dose of 10 mg/kg of cyclosporine, Cmax and AUC0-5 of cyclosporine were found to be significantly elevated. Therefore, caution should be exercised before concurrent administration of these drugs is considered. If co-administration of these drugs is necessary, ciclosporin levels should be monitored and the dose adjusted accordingly.

Efavirenz: Co-administration of a single dose of azithromycin 600 mg and efavirenz 400 mg daily for 7 days did not result in clinically significant pharmacokinetic interactions.

Fluconazole: Co-administration of a single dose of 1200 mg of azithromycin does not change the pharmacokinetics of a single dose of 800 mg of fluconazole. The total exposure and half-life of azithromycin did not change when co-administered with fluconazole, however, there was a clinically insignificant decrease in Cmax (18%) of azithromycin.

Indinavir: Co-administration of a single dose of 1200 mg of azithromycin had no statistically significant effect on the pharmacokinetics of indinavir administered at a dosage of 800 mg three times a day for 5 days.

Methylprednisolone: In a pharmacokinetic interaction study in healthy volunteers, azithromycin showed no significant effect on the pharmacokinetics of methylprednisolone.

Midazolam: In healthy volunteers, co-administration with azithromycin 500 mg/day for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of a single dose of 15 mg midazolam.

Nelfinavir: Co-administration of azithromycin (1200 mg) and nelfinavir at steady state (750 mg three times a day) resulted in an increase in azithromycin concentrations. No clinically significant side effects were observed and dose adjustment is not required.

Rifabutin: The simultaneous use of azithromycin and rifabutin did not affect the concentration of these drugs in the blood plasma.

Neutropenia was detected with the simultaneous use of azithromycin and rifabutin. Although neutropenia has been associated with the use of rifabutin, a causal relationship with concomitant use of azithromycin has not been established.

Sildenafil: In normal healthy male volunteers, there is no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC and Cmax of sildenafil or its major circulating metabolite.

Terfenadine: No interactions between azithromycin and terfenadine have been reported in pharmacokinetic studies. In some cases, it is not possible to completely eliminate the possibility of an interaction. However, there was no concrete evidence that such an interaction took place.

Theophylline: There is no evidence of a clinically significant pharmacokinetic interaction between azithromycin and theophylline when administered concomitantly to healthy volunteers.

Triazolam: In 14 healthy volunteers, co-administration of azithromycin 500 mg on day 1 and 250 mg on day 2 with triazolam 0.125 mg on day 2 had no significant effect on any of the pharmacokinetic variables for triazolam compared with co-administration of triazolam and placebo.

Trimethoprim/sulfamethoxazole: Co-administration of trimethoprim/sulfamethoxazole DS (160 mg/800 mg) for 7 days with azithromycin 1200 mg on day 7 had no significant effect on peak concentration, total exposure, or elimination of trimethoprim or sulfamethoxazole. Serum azithromycin concentrations were similar to those observed in other studies.

special instructions

As with erythromycin and other macrolides, rare serious allergic reactions have been reported, including angioedema and anaphylaxis (rarely fatal). Some of these reactions to azithromycin lead to the development of recurrent symptoms and require a longer period of observation and treatment.

The liver is the main organ for the elimination of azithromycin, so azithromycin should be used with caution in patients with severe liver disease. Cases of fulminant hepatitis potentially leading to life-threatening liver failure have been reported.

Some patients may have had existing medical conditions

liver or they were taking other hepatotoxic drugs.

If signs and symptoms of liver dysfunction occur, such as rapidly developing asthenia associated with jaundice, dark urine, bleeding tendency, or hepatic encephalopathy, perform liver function tests/tests immediately.

With the development of liver dysfunction, stop taking azithromycin.

In patients receiving ergot derivatives, the appearance of ergotism is provoked by the simultaneous administration of certain macrolide antibiotics. There are no data on the possibility of an interaction between ergot and azithromycin. However, due to the theoretical possibility of ergotism, azithromycin and ergot derivatives are taken separately.

diarrhea caused by Clostridium difficile has been reported in all cases of use of antibacterial agents, including azithromycin, and can range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal intestinal flora, leading to overgrowth C. difficile.

C. difficile produces toxins A and B, which contribute to the development of CDAD. A strain that produces hypertoxin C. difficile lead to increased morbidity and mortality as these infections may be resistant to antimicrobial therapy and may require treatment

colectomy. CDAD should be considered in all patients who complain of diarrhea after antibiotic use. A careful history is essential, as CDAD may develop up to two months after administration of antibacterial agents.

In patients with severe renal insufficiency (GFR<10 мл / мин) наблюдалось 33% увеличение системного воздействия азитромицина.

Prolonged cardiac repolarization and prolongation of the QT interval, leading to the risk of developing cardiac arrhythmias and bidirectional tachycardia, have been reported with other macrolides, including azithromycin. The following conditions increase the risk of developing ventricular arrhythmias (including bidirectional tachycardia), which can lead to cardiac arrest, so azithromycin should be used with caution in patients with current proarrhythmic conditions (especially women and elderly patients), for example:

With congenital or documented QT prolongation

Who are currently being treated with other active substances known to prolong the QT interval, such as class IA antiarrhythmics (quinidine and procainamide) and class III antiarrhythmics (dofetilide, amiodarone and sotalol), cisapride and terfenadine; antipsychotics such as pimozide; antidepressants such as citalopram; and fluoroquinolones such as moxifloxacin and levofloxacin

With electrolyte imbalance, especially in cases of hypokalemia and hypomagnesemia

With clinically significant bradycardia, cardiac arrhythmias, or severe heart failure.

Exacerbation of myasthenia symptoms and new onset of myasthenia gravis have been reported in patients receiving azithromycin.

Penicillin is generally the drug of choice for the treatment of laryngitis/tonsillitis caused by Streptococcus pyogenes and is used as prophylaxis in acute rheumatic fever. Azithromycin is generally effective against streptococcal pharyngitis, but there is no information regarding its effectiveness in preventing acute rheumatic fever.

The safety and efficacy of intravenous azithromycin for the treatment of infections in children have not been established.

The safety and efficacy of Mycobacterium Avium Complex for prophylaxis or treatment in children have not been established.

Sucrose.

The drug contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption syndrome or sucrase-isomaltase insufficiency should not take this medicine.

Pregnancy

The use of the drug during pregnancy is possible when the expected benefit outweighs the potential risk to the fetus.

Features of the influence of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

Sumamed® does not affect the reaction rate when driving vehicles and working with other mechanisms.

Overdose

There are no data on overdose of Sumamed®. An overdose of macrolide antibiotics is manifested by nausea, vomiting and diarrhea. In case of an overdose, it is necessary to take activated charcoal and carry out symptomatic therapy aimed at maintaining the vital functions of the body.

Release form and packaging

The drug should be stored out of the reach of children at a temperature not exceeding 25°C.

Expiry date from date of manufacture

2 years. Prepared suspension - 5 days

pharmachologic effect

Bacteriostatic antibiotic of the macrolide-azalide group. It has a wide spectrum of antimicrobial activity. The mechanism of action of azithromycin is associated with the suppression of protein synthesis of microbial cells. By binding to the 50S subunit of the ribosome, it inhibits the peptide translocase at the translation stage and inhibits protein synthesis, slowing down the growth and reproduction of bacteria. In high concentrations, it has a 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 an antibiotic or may acquire resistance to it.
In most cases, Sumamed® is active against aerobic gram-positive bacteria: Staphylococcus aureus (methicillin-sensitive strains), Streptococcus pneumoniae (penicillin-sensitive strains), Streptococcus pyogenes; aerobic gram-negative bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis, Pasteurella multocida, Neisseria gonorrhoeae; anaerobic bacteria: Clostridium perfringens, Fusobacterium spp., Prevotella spp., Porphyromonas spp.; 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, Staphylococci (methicillin-resistant strains of staphylococcus show a very high degree of resistance to macrolides); gram-positive bacteria resistant to erythromycin; anaerobes - Bacteroides fragilis.

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 through histohematic barriers and enters the tissues. The concentration in tissues and cells is 10-50 times higher than in plasma, and in the focus of infection it is 24-34% higher than in healthy tissues.
Metabolism
Demethylated in the liver, losing activity.
breeding
T1 / 2 is very long - 35-50 hours. T1 / 2 from tissues is much larger. The therapeutic concentration of azithromycin is maintained up to 5-7 days after the last dose. Azithromycin is excreted mainly unchanged - 50% through the intestines, 6% by the kidneys.

Indications for use

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

Use during pregnancy and lactation

During pregnancy and during breastfeeding, the use of the drug is possible only if the expected potential benefit of therapy for the mother outweighs the potential risk to the fetus and child.
If necessary, the use of the drug during lactation, breastfeeding should be suspended.

special instructions

In case of missing one dose of the drug, the missed dose should be taken as soon as possible, and subsequent doses should be taken at intervals of 24 hours.
Sumamed should be taken at least 1 hour before or 2 hours after taking antacids.
Sumamed should be used with caution in patients with mild to moderate hepatic impairment due to the possibility of developing fulminant hepatitis and severe hepatic failure. If there are symptoms of impaired liver function, such as rapidly increasing asthenia, jaundice, dark urine, a tendency to bleeding, hepatic encephalopathy, Sumamed® therapy 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 Sumamed® 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 Sumamed®, patients should be regularly examined for the presence of non-susceptible microorganisms and signs of the development of superinfections, incl. fungal.
The drug Sumamed® should not be used for longer courses than indicated in the instructions, because. The pharmacokinetic properties of azithromycin allow a short and simple dosing regimen to be recommended.
There is no evidence of a possible interaction between azithromycin and ergotamine and dihydroergotamine derivatives, but due to the development of ergotism while using macrolides with ergotamine and dihydroergotamine derivatives, this combination is not recommended.
With prolonged use of the drug Sumamed®, it is possible to develop pseudomembranous colitis caused by Clostridium difficile, both in the form of mild diarrhea and severe colitis. With the development of antibiotic-associated diarrhea while taking the drug Sumamed®, 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, there was an increase in cardiac repolarization and the QT interval, which increase the risk of developing cardiac arrhythmias, incl. pirouette-type arrhythmias.
Caution should be exercised when using the drug Sumamed® in patients with the presence of proarrhythmic factors (especially in elderly patients), incl. with congenital or acquired prolongation of the QT interval; in patients taking antiarrhythmic drugs of classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotics (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), in patients with impaired 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 Sumamed® can provoke the development of myasthenic syndrome or cause an exacerbation of myasthenia gravis.
When used in patients with diabetes mellitus, as well as in patients on a low-calorie diet, it must be taken into account that the powder for the preparation of the Sumamed® suspension contains sucrose (0.32 XU / 5 ml) as an auxiliary substance.
Influence on the ability to drive vehicles and control 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 an increased concentration of attention and speed of psychomotor reactions.

With caution (Precautions)

myasthenia; liver dysfunction of mild and moderate severity; terminal renal failure with GFR less than 10 ml/min; in patients with the presence of proarrhythmic factors (especially in the elderly) - with congenital or acquired prolongation of the QT interval, in patients receiving therapy with antiarrhythmic drugs of classes IA (quinidine, procainamide) and III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotics drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with impaired water and electrolyte balance, especially with hypokalemia or hypomagnesemia, with clinically significant bradycardia, arrhythmia, or with severe heart failure; with the simultaneous use of digoxin, warfarin, cyclosporine; diabetes mellitus (for powder for suspension preparation).

Contraindications

Hypersensitivity to azithromycin, erythromycin, other macrolides or ketolides, or other components of the drug;
- severe liver dysfunction;
- simultaneous reception with ergotamine and dihydroergotamine;
- children's age up to 6 months (for powder for suspension preparation);
- sucrase / isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption (for powder for suspension preparation).

Dosage and administration

Assign to children aged 6 months to 3 years.
The suspension is administered orally 1 time / day, 1 hour before or 2 hours after a meal. After taking the drug Sumamed®, the child must be offered to drink a few sips of water so that he can swallow the rest of the suspension.
Before each dose of the drug, the contents of the vial are thoroughly shaken until a homogeneous suspension is obtained. If the required volume of the suspension was not taken from the vial within 20 minutes after shaking, the suspension should be shaken again, the required volume should be taken and given to the child.
The required dose is measured using a dosing syringe with a division value of 1 ml and a nominal suspension capacity of 5 ml (100 mg azithromycin) or a measuring spoon with a nominal suspension capacity of 2.5 ml (50 mg azithromycin) or 5 ml (100 mg azithromycin) inserted in a cardboard packaging along with the vial.
After use, the syringe (having previously disassembled it) and the measuring spoon are washed with running water, dried and stored in a dry place until the next dose of Sumamed®.
For 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 / day for 3 days (course dose 30 mg / kg). For accurate dosing of the drug Sumamed® in accordance with the body weight of the child, use the table below. With pharyngitis / tonsillitis caused by Streptococcus pyogenes, Sumamed® is prescribed at a dose of 20 mg / kg / day for 3 days. Heading dose - 60 mg / kg. The maximum daily dose is 500 mg.
In Lyme disease (the initial stage of borreliosis) - migrating erythema (erythema migrans) is prescribed on the 1st day at a dose of 20 mg / kg 1 time / day, then from 2 to 5 days - at the rate of 10 mg / kg / day. Heading dose - 60 mg / kg.
Suspension preparation and storage method
To the contents of the vial intended for the preparation of 20 ml suspension (nominal volume), 12 ml of water is added using a dosing syringe and shaken until a homogeneous suspension is obtained. The volume of the resulting suspension will be about 25 ml, which exceeds the nominal volume by about 5 ml. This is provided to compensate for the inevitable losses of the suspension when dosing the drug. The prepared suspension can be stored at a temperature not exceeding 25°C for no more than 5 days.
In case of impaired renal function: in patients with GFR 10-80 ml / min, dose adjustment is not required.
In case of impaired liver function: when used in patients with mild to moderate hepatic impairment, dose adjustment is not required.
Elderly patients: dose adjustment is not required. Since the elderly may already have current proarrhythmic conditions, caution should be exercised when using the drug Sumamed® due to the high risk of developing cardiac arrhythmias, incl. pirouette-type arrhythmias.

Overdose

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

Side effect

The frequency of side effects is classified in accordance with WHO recommendations: very often (≥10%), often (≥1% - Infectious diseases: infrequently - candidiasis (including the oral mucosa and genitals), pneumonia, pharyngitis, gastroenteritis, respiratory diseases, rhinitis; unknown frequency - pseudomembranous colitis.
On the part of the blood and lymphatic system: 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, taste disturbance, paresthesia, 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.
On the part of the organ of vision: infrequently - visual impairment.
On the part of the organ of hearing and labyrinth disorders: infrequently - hearing loss, 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 blood to the face; unknown frequency - a decrease in blood pressure, an 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 side of the liver and biliary tract: infrequently - hepatitis; rarely - impaired liver function, 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.
On the part of the skin and subcutaneous tissues: infrequently - skin rash, itching, urticaria, dermatitis, dry skin, sweating; rarely - a 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 side of the kidneys and urinary tract: infrequently - dysuria, pain in the kidneys; unknown frequency - interstitial nephritis, acute renal failure.
From the genital organs and mammary gland: infrequently - metrorrhagia, impaired testicular function.
Others: infrequently - asthenia, malaise, feeling of fatigue, swelling of the face, 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 , increase in blood glucose concentration, increase in platelet count, increase in hematocrit, increase in plasma bicarbonate concentration, change in plasma sodium content.

Compound

Azithromycin dihydrate** 25.047 mg, which corresponds to the content of azithromycin 23.895 mg. Excipients: sucrose ** - 929.753 mg, sodium phosphate - 20 mg, hyprolose - 1.6 mg, xanthan gum - 1.6 mg, strawberry flavor - 10 mg, titanium dioxide - 5 mg, colloidal silicon dioxide - 7 mg.
20.925 g - 50 ml high-density polyethylene bottles (1) with a polypropylene resistant cap, complete with a measuring spoon and / or syringe for dosing - cardboard packs.
* capsules contain sulfur dioxide 200 ppm as a preservative;
** values ​​are given based on the theoretical activity of the substance 95.4%; the amount of sucrose may vary depending on the actual activity of azithromycin.

Interaction with other drugs

Antacids
Antacids do not affect the bioavailability of azithromycin, but reduce Cmax in the blood by 30%, so Sumamed® should be taken at least 1 hour before or 2 hours after taking these drugs and eating.
Cetirizine
The 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 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)
Simultaneous use of macrolide antibiotics, incl. azithromycin, with substrates of P-glycoprotein, 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
The simultaneous use of azithromycin (single dose of 1000 mg and multiple doses of 1200 mg or 600 mg) has little effect on pharmacokinetics, incl. renal excretion of zidovudine or its glucuronide metabolite. However, the use of azithromycin caused 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.
Azithromycin weakly interacts with isoenzymes of the cytochrome P450 system. It has not been revealed that azithromycin is involved in a pharmacokinetic interaction similar to erythromycin and other macrolides. Azithromycin is not an inhibitor and inducer of isoenzymes of the cytochrome P450 system.
Ergot alkaloids
Given the theoretical possibility of ergotism, the simultaneous use of azithromycin with ergot alkaloid derivatives is not recommended.
Pharmacokinetic studies have been conducted on the simultaneous use of azithromycin and drugs whose metabolism occurs with the participation of isoenzymes of the cytochrome P450 system.
Atorvastatin
Co-administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter plasma concentrations of atorvastatin (based on MMC-CoA reductase inhibition assay). However, in the post-registration period, there have been isolated reports of cases of rhabdomyolysis in patients receiving both 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 plasma in patients who received azithromycin concomitantly.
Cimetidine
In pharmacokinetic studies of the effect of cimetidine when taken in a single dose on the pharmacokinetics of azithromycin, there were no changes in the pharmacokinetics of azithromycin, provided that cimetidine was used 2 hours before azithromycin.
Indirect anticoagulants (coumarin derivatives)
In pharmacokinetic studies, azithromycin did not affect the anticoagulant effect of warfarin when administered as a single 15 mg dose to healthy volunteers. Potentiation of the anticoagulant effect has been reported after the 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 using azithromycin in patients receiving indirect oral anticoagulants (coumarin derivatives).
Cyclosporine
In a pharmacokinetic study in healthy volunteers who took oral azithromycin (500 mg/day once) and then cyclosporine (10 mg/kg/day once) for 3 days, a significant increase in plasma Cmax and AUC0-5 of cyclosporine was found. . Caution should be exercised when these drugs are used concomitantly. If it is necessary to use these drugs simultaneously, the concentration of cyclosporine in the blood plasma should be monitored and the dose adjusted accordingly.
Efavirenz
The 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
The simultaneous use of azithromycin (1200 mg once) did not change the pharmacokinetics of fluconazole (800 mg once). The total exposure and T1 / 2 of azithromycin did not change with the simultaneous use of fluconazole, however, a decrease in Cmax of azithromycin (by 18%) was observed, which had no clinical significance.
indinavir
The simultaneous use of azithromycin (1200 mg once) did 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 of methylprednisolone.
Nelfinavir
The simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times / day) causes an increase in Css of azithromycin in plasma. No clinically significant side effects were observed and no dose adjustment of azithromycin was required when co-administered with nelfinavir.
Rifabutin
The simultaneous use of azithromycin and rifabutin does not affect the concentration of each of the drugs in the blood plasma. With the simultaneous use of azithromycin and rifabutin, neutropenia was sometimes observed. Although neutropenia has been associated with the use of rifabutin, a causal relationship between the use of the combination of azithromycin and rifabutin and neutropenia has not been established.
Sildenafil
When used in healthy volunteers, there was no evidence of the effect of azithromycin (500 mg / day for 3 days) on the AUC and Cmax of sildenafil or its main circulating metabolite.
Terfenadine
In pharmacokinetic studies, there was no evidence of an interaction between azithromycin and terfenadine. Isolated cases have been reported where the possibility of such an interaction could not be completely ruled out, but there was no concrete evidence that such an interaction took place. It has been found that the simultaneous use of terfenadine and macrolides can cause arrhythmia and prolongation of the QT interval.
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 have not been identified.
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.

Release form

Powder for suspension for oral administration 100 mg / 5 ml from white to yellowish-white in color, with a characteristic strawberry odor; after dissolution in water - a homogeneous suspension of yellowish-white color, with a characteristic smell of strawberries.