Azithromycin Ecomed® powder 200 mg / 5 ml bottle

Instructions for use of Azithromycin Ecomed® powder 200 mg / 5 ml bottle

Trade name: Azithromycin ECOMED

International Nonproprietary Name: Azithromycin

Dosage form: Powder for oral suspension

Composition per 5 ml of suspension

5 ml of the prepared suspension (one dosing spoon) contains:

• Active substances
• Azithromycin dihydrate (calculated as azithromycin) 100 mg 200 mg
• Excipients
• Lactitol 200.0 mg 400.0 mg
• Xanthan gum 15.0 mg 15.0 mg
• Croscarmellose sodium (Kollidon CL-M) 65.0 mg 65.0 mg
• Colloidal silicon dioxide (Aerosil) 5.5 mg 5.5 mg
• Anhydrous sodium carbonate 83.0 mg 83.0 mg
• Sodium benzoate 16.5 mg 16.5 mg
• Titanium dioxide 10.0 mg 10.0 mg
• Mint flavor 0.5 mg 0.5 mg
• Strawberry flavor 55.0 mg 55.0 mg
• Apple flavor 13.75 mg 13.75 mg
• Cinnamon flavor 13.75 mg 13.75 mg
• Sucrose up to a weight of 3.75 g 3.75 g

Description:

Powder: white or yellowish-white powder with a faint fruity odor. Prepared suspension: white to light yellow, homogeneous with a faint fruity odor.

Pharmacotherapeutic group: Antibiotic - azalide

ATC Code: J01FA10

Pharmacological Properties

Antibacterial drug with a broad spectrum of activity from the macrolide-azalide group; exerts bacteriostatic action. By binding to the 50S ribosomal subunit, it inhibits peptidyl transferase during translation, suppresses protein synthesis, slows bacterial growth and reproduction, and exerts bactericidal effect at high concentrations. Active against extracellular and intracellular pathogens.

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

Susceptibility scale of microorganisms to azithromycin (Minimum Inhibitory Concentration (MIC), mg/l):

Microorganisms

MIC, mg/l

Susceptible Resistant

Staphylococcus ≤ 1 > 2

Streptococcus A, B, C, G ≤ 0.25 > 0.5

Streptococcus pneumoniae ≤ 0.25 > 0.5

Haemophilus influenzae ≤ 0.12 > 4

Moraxella catarrhalis ≤ 0.5 > 0.5

Neisseria gonorrhoeae ≤ 0.25 > 0.5

Susceptible:

Aerobic Gram-positive microorganisms:

• Staphylococcus aureus (methicillin-susceptible)
• Streptococcus pneumoniae (penicillin-susceptible)
• Streptococcus pyogenes

Aerobic Gram-negative microorganisms:

• Haemophilus influenzae
• Haemophilus parainfluenzae
• Legionella pneumophila
• Moraxella catarrhalis
• Pasteurella multocida
• Neisseria gonorrhoeae

Anaerobic microorganisms:

• Clostridium perfringens
• Fusobacterium spp.,
• Prevotella spp.,
• Porphyromonas spp.

Other:

• Chlamydia trachomatis
• Chlamydia pneumoniae
• Chlamydia psittaci
• Mycoplasma pneumoniae
• Mycoplasma hominis
• Borrelia burgdorferi

Moderately susceptible or not susceptible:

Aerobic Gram-positive microorganisms:

• Streptococcus pneumoniae (moderately susceptible or resistant to penicillin)

Resistant:

Aerobic Gram-positive microorganisms:

• Enterococcus faecalis
• Staphylococci spp. (methicillin-resistant)

Anaerobes:

• Bacteroides fragilis group

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

Pharmacokinetics

After oral administration, azithromycin is well absorbed and rapidly distributed in the body. Bioavailability after a single 0.5 g dose is 37% (first-pass effect), maximum concentration (Cmax) after oral administration of 0.5 g is 0.4 mg/l, time to reach maximum concentration (Tmax) is 2-3 hours. Concentration in tissues and cells is 10-50 times higher than in serum. Volume of distribution is 31.1 l/kg, plasma protein binding is inversely proportional to blood concentration and ranges from 7-50%. Azithromycin is acid-stable and lipophilic. It easily passes through tissue barriers, penetrates well into the respiratory tract, internal organs and tissues, including the prostate gland, skin and soft tissues. It is also transported to the site of infection by phagocytes, polymorphonuclear leukocytes, and macrophages, where it is released in the presence of bacteria. It penetrates cell membranes and creates high concentrations within them, which is especially important for eradicating intracellular pathogens.

Concentration at the site of infection is 24-34% higher than in healthy tissues and correlates with the severity of the inflammatory process. It remains at effective concentrations for 5-7 days after the last dose.

It is demethylated in the liver; the resulting metabolites are inactive. The drug's metabolism involves isoenzymes CYP3A4, CYP3A5, CYP3A7, which it inhibits. Plasma clearance is 630 ml/min; half-life between 8 and 24 hours after administration is 14-20 hours, half-life in the interval from 24 to 72 hours is 41 hours. More than 50% of the drug is excreted unchanged through the intestines, 6% by the kidneys.

Food intake significantly alters pharmacokinetics: Cmax increases (by 31%), the area under the concentration-time curve (AUC) does not change.

In elderly men (65-85 years), pharmacokinetic parameters do not change; in women, Cmax increases (by 30-50%).

Indications for Use

Infectious and inflammatory diseases caused by microorganisms susceptible to azithromycin:

• Infections of the upper respiratory tract and ENT organs: pharyngitis, tonsillitis, sinusitis, otitis media;
• Infections of the lower respiratory tract: 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;
• Initial stage of Lyme disease (borreliosis) – erythema migrans.

Contraindications

• Hypersensitivity to azithromycin (including other macrolides) or other components of the drug; severe renal failure (creatinine clearance (CrCl) less than 40 ml/min);
• Severe hepatic failure (Child-Pugh class C);
• Breastfeeding;
• Concurrent use with ergotamine and dihydroergotamine;
• Children under 6 months of age;
• Sucrase/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption.

Use with Caution

• Renal failure (creatinine clearance (CrCl) greater than 40 ml/min);
• Hepatic failure (Child-Pugh class A and B);
• In cases of arrhythmias or predisposition to arrhythmias and QT interval prolongation;
• With concurrent use of terfenadine, warfarin, digoxin;
• Myasthenia gravis.

Use During Pregnancy and Lactation

Azithromycin during pregnancy is recommended only when the expected benefit to the mother outweighs the potential risk to the fetus. Breastfeeding should be discontinued during azithromycin treatment.

Dosage Regimen

Azithromycin ECOMED in the form of an oral suspension is prescribed to children from 6 months of age.

3-day course: 10 mg/kg once daily (total course dose 30 mg/kg).

5-day course: For Lyme disease (borreliosis) for the treatment of stage I (erythema migrans) in children, the dose is 20 mg/kg on the first day and 10 mg/kg from day 2 to day 5 of the illness;

total course dose 60 mg/kg.

Method of Suspension Preparation

The suspension should be prepared immediately before use.

Shake the powder in the bottle, add 12 ml of boiled and cooled water at room temperature using the dosing syringe, and mix to obtain a homogeneous suspension. For accurate dosing of the suspension, use the double-ended dosing spoon or syringe provided, which should be rinsed thoroughly with water after each use.

After reconstitution, the prepared suspension should be stored for no more than 5 days in the refrigerator, but not frozen.

Adverse Reactions

• Gastrointestinal disorders: nausea, vomiting, diarrhea, abdominal pain, loose stools, flatulence, indigestion, anorexia, constipation, tongue discoloration, pseudomembranous colitis, cholestatic jaundice, hepatitis, changes in liver function tests, hepatic failure, liver necrosis (possibly fatal), hyperbilirubinemia, pancreatitis, fulminant hepatitis.
• Allergic reactions: itching, skin rash, angioedema, urticaria, photosensitivity, anaphylactic reaction (in rare cases fatal), erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
• Cardiac disorders: palpitations, arrhythmia, ventricular tachycardia, prolonged QT interval, bidirectional ventricular tachycardia, decreased blood pressure.
• Nervous system disorders: dizziness/vertigo, headache, convulsions, somnolence, paresthesia, asthenia, insomnia, hyperactivity, aggressiveness, anxiety, nervousness, syncope, myasthenia gravis.
• Ear and labyrinth disorders: tinnitus, reversible hearing impairment up to deafness (with long-term use of high doses), taste and smell perception disorders, blurred vision.
• Blood and lymphatic system disorders: thrombocytopenia, neutropenia, eosinophilia, lymphopenia, hemolytic anemia.
• Musculoskeletal and connective tissue disorders: arthralgia.
• Renal and urinary disorders: interstitial nephritis, acute renal failure, increased blood urea and creatinine.
• General disorders and administration site conditions: vaginitis, candidiasis, weakness, peripheral edema, malaise.

Overdose

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

Treatment: symptomatic.

Drug Interactions

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

With concurrent use of ergotamine and dihydroergotamine derivatives, an increase in the toxic effects of the latter (vasospasm, dysesthesia) is possible.

With concurrent use of coumarin indirect anticoagulants (warfarin), patients require careful monitoring of prothrombin time.

Caution should be exercised with the co-administration of terfenadine and azithromycin, as it has been established that simultaneous administration of terfenadine and macrolides causes arrhythmia and prolongation of the Q-T interval. Based on this, the aforementioned complications cannot be excluded with the simultaneous use of terfenadine and azithromycin.

With concurrent use of cyclosporine, it is necessary to monitor the concentration of cyclosporine in the blood. With concurrent use of digoxin, monitoring of digoxin blood concentration is necessary (increased absorption of digoxin in the intestine is possible).

With concurrent use of nelfinavir, an increase in the frequency of adverse reactions to azithromycin (hearing loss, increased activity of "liver" transaminases) is possible.

With concurrent use of zidovudine, azithromycin does not affect the pharmacokinetic parameters of zidovudine in blood plasma or its renal excretion and that of its metabolite, glucuronide, but increases the concentration of the active metabolite, phosphorylated zidovudine, in peripheral blood mononuclear cells. The clinical significance of this fact is unknown.

The possibility of inhibition of the CYP3A4 isoenzyme by azithromycin should be considered when used concomitantly with cyclosporine, terfenadine, ergot alkaloids, cisapride, pimozide, quinidine, astemizole, and other drugs metabolized by this enzyme.

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

Special Instructions

If a dose is missed, the missed dose should be taken as soon as possible, and subsequent doses should be taken at 24-hour intervals. Azithromycin should be taken 1 hour before or 2 hours after taking antacids. Use with caution in patients with moderate hepatic impairment due to the possibility of developing fulminant hepatitis and severe hepatic failure. If symptoms of liver dysfunction appear (rapidly increasing asthenia, jaundice, dark urine, tendency to bleed, hepatic encephalopathy), azithromycin therapy should be discontinued and liver function tests performed.

In moderate renal failure (CrCl greater than 40 ml/min), azithromycin should be used under monitoring of renal function.

Concurrent use of azithromycin with ergotamine and dihydroergotamine derivatives is contraindicated due to the possible development of ergotism. When using the drug, both during administration and 2-3 weeks after cessation of treatment, diarrhea caused by Clostridium difficile (pseudomembranous colitis) may develop. In mild cases, discontinuation of treatment and administration of ion-exchange resins (cholestyramine, colestipol) is sufficient; in severe cases, replacement of fluid, electrolyte, and protein losses, and administration of vancomycin, bacitracin, or metronidazole is indicated. Drugs that inhibit intestinal peristalsis should not be used.

Since prolongation of the Q-T interval is possible in patients receiving macrolides, caution should be exercised when using azithromycin in patients with known risk factors for Q-T interval prolongation: elderly age; electrolyte imbalance (hypokalemia, hypomagnesemia); congenital long QT syndrome; heart disease (heart failure, myocardial infarction, bradycardia); concurrent use of drugs that can prolong the Q-T interval (including class IA and III antiarrhythmic drugs, tricyclic and tetracyclic antidepressants, antipsychotics, fluoroquinolones).

When using azithromycin, the development of myasthenic syndrome or exacerbation of myasthenia gravis is possible.

Effects on Ability to Drive and Operate Machinery

During treatment, caution must be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Packaging

Powder for oral suspension 100 mg/5 ml, 200 mg/5 ml.

16.5 g in 60 ml dark glass bottles with a screw-on plastic cap.

1 bottle together with a double-ended dosing spoon (small capacity 2.5 ml, large - 5 ml), a dosing syringe, and instructions for use are placed in a cardboard carton.

Shelf Life

2 years.

Prepared suspension – 5 days.

Do not use after the expiration date.

Storage Conditions

Store in a dry place, protected from light, at a temperature not exceeding 25 °C.

The prepared suspension should be stored at a temperature of 2 °C to 8 °C in a tightly closed bottle.

Keep out of reach of children.

Legal Status

Prescription only.

Marketing Authorization Holder / Organization for Claims:

JSC "AVVA RUS", Russia, 121614, Moscow, ul. Krylatskie Kholmy, 30, building 9.

Tel/Fax: (495) 956-75-54.

www.avva-rus.ru

www.ecoantibiotic.ru

Production Site Address:

JSC "AVVA RUS", Russia, 610044, Kirov region, Kirov, ul. Luganskaya, 53a.

Tel: (8332) 25-12-29, (495) 956-75-54.

Consumer complaints should be sent to the manufacturer's address.