Azithromycin-Vertex, 125 mg 6 pcs

An antibiotic of the macrolide group, it is a representative of azalides. It has a wide range of antimicrobial action. The mechanism of action of azithromycin is associated with inhibition of microbial cell protein synthesis. Binding to 50S subunit of ribosomes, it inhibits peptide translocation stage, inhibits protein synthesis, slows down growth and reproduction of bacteria. It acts bacteriostatic. At high concentrations it has a bactericidal effect.

Azithromycin is sensitive to Gram-positive cocci: Streptococcus pneumoniae (penicillin-sensitive strains), Streptococcus pyogenes, Staphylococcus aureus (methicillin-sensitive strains); aerobic Gram-negative bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis, Pasteurella multocida, Neisseria gonorrhoeae; some anaerobic microorganisms: Clostridium perfringens, Fusobacterium spp., Prevotella spp., Porphyriomonas spp.; and Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.

Microorganisms with acquired resistance to azithromycin: aerobic gram-positive microorganisms -Streptococcus pneumoniae (penicillin-resistant strains and strains with moderate sensitivity to penicillin).

Microorganisms with natural resistance: aerobic gram-positive microorganisms – Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis (methicillin-resistant strains), anaerobic microorganisms – Bacteroides fragilis.

Cases of cross-resistance between Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococcus), Enterococcus faecalis and Staphylococcus aureus (methicillin-resistant strains) to erythromycin, azithromycin, other macrolides and Lincosamides have been described.

Asithromycin has not been used to treat infections caused by Salmonella typhi (MIC < 16 mg/l) and Shigella spp.

Pharmacokinetics

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

Protein binding is inversely proportional to plasma concentration and is 7-50%. The apparent V_d is 31.1 l/kg. It penetrates through cell membranes (effective in 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 the histohematic barriers and enters the tissues. Concentration in tissues and cells is 10-50 times higher than in plasma and 24-34% higher in the focus of infection than in healthy tissues.

The drug is metabolized in the liver. Metabolites have no antimicrobial activity.

T_1/2 is very long, 35-50 h. T_1/2 from tissues is much longer. The therapeutic concentration of azithromycin is maintained up to 5-7 days after the last dose. Azithromycin is excreted mainly unchanged – 50% through the intestine, 6% by the kidneys.

After intravenous infusion, azithromycin rapidly penetrates from serum to tissues. Concentrated in phagocytes and without affecting their function, azithromycin migrates to the focus of inflammation, accumulating directly in infected tissues.

The pharmacokinetics of azithromycin in healthy volunteers after a single IV infusion lasting more than 2 hours at a dose of 1-4 g (solution concentration 1 mg/ml) has a linear dependence and is proportional to the administered dose.

In healthy volunteers, the C_max in serum was 1.14 µg/mL when azithromycin was infused intravenously at a dose of 500 mg (solution concentration 1 mg/mL) for 3 h. C_min in serum (0.18 µg/mL) was noted for 24 h and the AUC was 8.03 µg×mL/h. Similar pharmacokinetic values were obtained in patients with community-acquired pneumonia who received 3-hour IV infusions for 2 to 5 days. V_d is 33.3 L/kg.

After administration of azithromycin daily at a dose of 500 mg (1-hour infusion duration) for 5 days, an average of 14% of the dose is excreted by the kidneys over a 24-hour dosing interval.

The T_1/2 is 65-72 h. The large V_d (33.3 L/kg) and high plasma clearance (10.2 ml/min/kg) suggest that the long T_1/2 is a consequence of accumulation of the antibiotic in tissues followed by its slow release.

Indications

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

– infections of the upper respiratory tract and ENT organs: pharyngitis, tonsillitis, sinusitis, otitis media;

– lower respiratory tract infections: acute bronchitis, exacerbation of chronic bronchitis, pneumonia, including. caused by atypical pathogens;

– skin and soft tissue infections: common acne of moderate severity, rye, impetigo, secondary infected dermatoses;

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

– infections of the urogenital tract, caused by Chlamydia trachomatis (urethritis, cervicitis).

Active ingredient

Composition

The composition of 1 tablet includes:

The active ingredients are:

azithromycin (in the form of dihydrate) – 125 mg,

Excipients:

Microcrystalline cellulose – 9 mg,

lactose monohydrate – 8.366 mg,

povidone (K-30) – 6.5 mg,

crospovidone – 6.5 mg,

sodium lauryl sulfate – 0.325 mg,

colloidal silicon dioxide – 1.65 mg,

magnesium stearate – 1.65 mg.

Particle film composition: hypromellose – 3 mg, talc – 1 mg, titanium dioxide – 0.55 mg, macrogol 4000 – 0.45 mg.

How to take, the dosage

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

In infections of upper and lower respiratory tract, ENT organs, skin and soft tissue: 500 mg 1 time/day for 3 days (course dose – 1.5 г).

In Moderate acne: 2 capsules. 250 mg once a day for 3 days, then 250 mg twice a week for 9 days. The course dose is 6.0 g.

In emerging erythema:On the first day, 2 capsules of 500 mg at a time, then from day 2 to day 5, 500 mg daily. The course dose is 3.0 g.

In infections of the urogenital tract caused by Chlamydia trachomatis (urethritis, cervicitis): One day 2 capsules of 500 mg.

Prescribing to patients with renal dysfunction: for patients with moderate renal dysfunction (CK > 40 ml/min), no correction is necessary.

Interaction

Parenterally, azithromycin does not affect plasma concentrations of cimetidine, efavirenz, fluconazole, indinavir, midazolam, triazolam, co-trimoxazole (sulfamethoxazole + trimethoprim) when used together, but the possibility of such interactions should not be excluded when azithromycin is administered orally.

If co-administration with cyclosporine is necessary, it is recommended to monitor blood levels of cyclosporine.

When digoxin and azithromycin are coadministered, the blood digoxin concentration must be monitored because many macrolides increase digoxin absorption in the intestine, thereby increasing its plasma concentration.

If co-administration with warfarin is necessary, careful monitoring of prothrombin time is recommended.

The concomitant use of terfenadine and macrolide class antibiotics causes arrhythmias and prolongation of the QT interval. Therefore, the above complications cannot be excluded when terfenadine and azithromycin are taken together. Since there is a possibility of inhibition of CYP3A4 isoenzyme by azithromycin in parenteral form when used together with cyclosporine, terfenadine, ergot alkaloids, cisapride, pimozide, quinidine, astemizole and other drugs metabolized with participation of this isoenzyme, the possibility of such interaction should be considered when prescribing azithromycin for oral administration.

When azithromycin and zidovudine are used together, azithromycin does not affect pharmacokinetic parameters of zidovudine in blood plasma or excretion of zidovudine and its glucuronized metabolite by kidneys. However, the concentration of the active metabolite, phosphorylated zidovudine, in mononuclear cells of peripheral vessels is increased. The clinical significance of this fact is unclear.

The simultaneous use of macrolides with ergotamines and dihydroergotamine may cause their toxic effects.

Special Instructions

After discontinuation of azithromycin therapy, hypersensitivity reactions may persist for a long time in some patients and may require specific therapy under medical supervision.

Influence on driving and operating machinery

In view of the possibility of CNS side effects, caution should be exercised when driving vehicles and operating machinery.

Contraindications

– children under 12 years of age with body weight less than 45 kg (for this dosage form);

– Breast-feeding;

– simultaneous use with ergotamine and dihydroergotamine;

– hypersensitivity to antibiotics of the macrolide group.

With cautiousness

– moderate hepatic and renal dysfunction;

– In arrhythmias or predisposition to arrhythmias and QT interval prolongation;

– In co-administration of terfenadine, warfarin, digoxin.

Side effects

Allergic reactions:Itching, skin rashes, angioneurotic edema, urticaria, photosensitization, anaphylactic reaction (in rare cases with fatal outcome), erythema multiforme, Stevens-Johnson syndrome, toxic epidermal nscrolisis.

Cardiovascular system disorders:Perception of palpitations, arrhythmias, ventricular tachycardia, prolonged QT interval, bidirectional ventricular tachycardia.

Nervous system disorders:dizziness/vertigo, headache, seizures, drowsiness, paraesthesia, asthenia, insomnia, hyperactivity, aggressiveness, restlessness, nervousness.

Sensory organs:Tinnitus, reversible hearing impairment to deafness (when taking high doses for a long time), disorders of taste and smell perception.

Hematological and lymphatic system disorders:thrombocytopenia, neutropenia, eosinophilia.

Motor system disorders:arthralgia.

Urogenital system disorders:interstitial nephritis, acute renal failure.

Others:vaginitis, candidiasis.

Overdose

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