Azitro

Azitro is a systemic antibacterial drug, belongs to the group of macrolide drugs.

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Indications Azitro

In doses of 100 mg/5 ml, as well as 200 mg/5 ml, it is used to eliminate infectious diseases caused by bacteria sensitive to azithromycin:

• pathologies of ENT organs (otitis media with tonsillitis or bacterial pharyngitis, as well as sinusitis);
• diseases of the respiratory system (community-acquired pneumonia, as well as bacterial bronchitis);
• infectious pathologies on the skin, as well as inside soft tissues (erysipelas, chronic erythema migrans (early stage of tick-borne borreliosis), and also secondary pyoderma).

The drug in doses of 200 mg / 5 ml is used to treat STIs (cervicitis or uncomplicated urethritis caused by the bacterium Chlamydia trachomatis).

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Release form

Available in powder form (16.5 g of substance) in a bottle for making a 20 ml suspension. Inside a separate pack there is 1 bottle, which is supplied with a dosing syringe and a special adapter.

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Pharmacodynamics

Azithromycin is a macrolide. It is an azalide with a wide range of antimicrobial action. The activity of the substance is due to the inhibition of the processes of binding microbial proteins by synthesis with the ribosomal 50 S-subunit, and also the prevention of peptide movement (in the absence of an effect on the process of binding polynucleotides). Basically, a bacteriostatic effect develops.

Resistance to azithromycin can be either innate or acquired. Complete cross-resistance for pneumococci, Staphylococcus aureus (including methicillin-resistant bacteria), fecal enterococci and β-hemolytic streptococci type A develops between the following substances: azithromycin with erythromycin, as well as other macrolides and lincomycins.

The following microbes are sensitive to azithromycin:

• gram-negative aerobes: Haemophilus parainfluenzae and influenza bacillus, as well as Moraxella catarrhalis;
• other bacteria: Legionella pneumophila, Chlamydia trachomatis, Chlamydophila pneumoniae and Mycoplasma pneumoniae, as well as Mycobacterium avium.

The types of bacteria that occasionally acquire resistance to the drug are gram-positive aerobes: Streptococcus agalactiae, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumococcus.

Bacteria that have innate resistance to the substance:

• Gram-positive aerobes: methicillin-resistant Staphylococcus epidermidis and Staphylococcus aureus, as well as Enterococcus faecalis;
• gram-negative aerobes: Klebsiella, Escherichia coli, and Pseudomonas aeruginosa;

Gram-negative anaerobes: Bacteroides fragilis group.

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Pharmacokinetics

After taking the drug, the bioavailability of the substance reaches approximately 37%. Peak serum levels are observed 2-3 hours after taking the suspension.

The substance is quickly distributed within the body's fluids and tissues. It passes perfectly into the tissues and organs of the genitourinary tract, respiratory tract and soft tissues with the skin. It accumulates inside the cells, as a result of which the drug indicator inside the tissues significantly exceeds similar plasma values (up to 50 times). This indicates that the drug has a high affinity in the tissues due to the weak synthesis of the substance with plasma protein.

The active ingredient levels inside target organs (the throat with lungs and prostate) are higher than MIC 90 for pathogenic substances when using a single dose of 500 mg. A large amount of azithromycin accumulates inside fibroblasts with phagocytes. The latter move the drug to the site of inflammation.

The medicine in its bactericidal values continues to remain in the area of inflammation for 5-7 days after the last dose, which makes it possible to carry out treatment in short courses - 3 or 5 days. The final half-life of the substance is similar to the time of its half-life from tissues, and is 2-4 days.

About 12% of the drug is excreted unchanged in urine over a period of 3 days. Large concentrations of unchanged substance are observed in bile. Ten decay products have been identified, which are formed by hydroxylation processes, as well as N- and O-demethylation, and other metabolic transformations. Azithromycin decay products do not have antimicrobial properties.

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Dosing and administration

The duration of therapy and the size of the dose are prescribed by the doctor. The suspension is taken once a day - 1 hour before meals or 2 hours after. This is necessary because simultaneous use with food disrupts the absorption of the active substance.

To improve the taste after taking the suspension, you can wash down the medicine with any fruit juice. If you miss a dose, try to take it as quickly as possible, and take all subsequent doses at intervals of 24 hours.

For adults (azithromycin in a proportion of 200 mg/5 ml):

• treatment of infectious diseases of the respiratory system and ENT organs, as well as soft tissues with skin (excluding chronic erythema migrans) - the total dose of the drug is 1500 mg. The drug is taken 500 mg once a day for 3 days;
• elimination of STDs caused by the bacterium Chlamydia trachomatis – a single dose of 1000 mg Azitro;
• Treatment of erythema migrans - the course lasts for 5 days. The total dosage of the drug is 3 g. On the first day, you need to take 1 g of the drug, and on the following days, take 500 mg of the suspension once a day.

Because elderly patients may be at risk for cardiac conduction disorders, caution is required when using azithromycin, as it may precipitate arrhythmia or torsades de pointes.

For children:

• treatment of infectious diseases in the respiratory system, ENT organs, as well as soft tissues with skin (excluding only chronic migratory erythema) - the total dose of the drug is 30 mg/kg over a 3-day course of therapy (a single daily dose in this case is 10 mg/kg);
• when eliminating erythema migrans - the total dosage of the drug is 60 mg / kg during a 5-day therapeutic course. The treatment regimen is as follows: on the 1st day, 20 mg / kg of the drug is taken, and then on the following days it is necessary to take 10 mg / kg once a day.

It turned out that Azitro is effective in eliminating streptococcal pharyngitis in children. The drug is taken once a day at a dose of 10 or 20 mg/kg for 3 days. Comparison of these dosages during clinical tests showed that their medicinal effectiveness is quite similar, but the destruction of bacteria in the case of taking a daily dose of 20 mg/kg was still more significant. But often for the prevention of pharyngitis caused by pyogenic streptococcus, as well as rheumatic polyarthritis, developing in the form of secondary pathology, penicillin is considered the drug of first choice.

Children weighing 5-15 kg (use of azithromycin at a dose of 100 mg/5 ml). The specified weight indicators require a special dosage regimen:

• weight 5 kg – the daily dose of suspension is 2.5 ml (the level of azithromycin in this dosage is 50 mg);
• weight 6 kg – the daily dose is 3 ml (azithromycin indicator – 60 mg);
• weight 7 kg – the daily dose is 3.5 ml (azithromycin level – 70 mg);
• weight 8 kg – daily dose is 4 ml (azithromycin indicator – 80 mg);
• weight 9 kg – daily dose is 4.5 ml (azithromycin level – 90 mg);
• weight 10-14 kg – daily dosage is 5 ml (active substance content – 100 mg).

For children weighing more than 15 kg (azithromycin is used in a ratio of 200 mg/5 ml). Taking into account the child's weight, the following dosage schemes are offered:

• weight within 15-24 kg – daily dose is 5 ml (azithromycin indicator – 200 mg);
• weight 25-34 kg – daily dose is 7.5 ml (active ingredient content – 300 mg);
• weight within 35-44 kg – the daily dosage is 10 ml (substance content – 400 mg);
• weight ≥45 kg – daily dose is 12.5 ml (azithromycin level – 500 mg).

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Use Azitro during pregnancy

The drug can pass through the placental barrier, but does not have a negative effect on the fetus. It should be noted that carefully controlled appropriate tests of the use of drugs in pregnant women have not been conducted. As a result, it is necessary to prescribe Azitro to pregnant women only in cases where the help from it for the woman is higher than the likelihood of complications in the fetus.

Azithromycin passes into breast milk, which is why it is necessary to stop breastfeeding for the period of the treatment course itself, as well as for another 2 days after its completion.

Contraindications

Among the contraindications:

• the presence of hypersensitivity to the active component or other elements of the drug or other macrolides and ketolide antibiotics;
• severe liver dysfunction;
• Since azithromycin in combination with ergot derivatives can theoretically cause ergotism, these drugs should not be combined.

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Side effects Azitro

Taking the suspension may cause the development of the following side effects:

• reactions of the hematopoietic system: hemolytic anemia, leukopenia or thrombocytopenia, and eosinophilia occasionally develop. Clinical tests have occasionally noted the occurrence of transient neutropenia with weak severity, but no connection between the use of azithromycin and the development of this disorder could be found;
• mental disorders: feelings of anxiety, aggression, nervousness or excitement occasionally appear, and in addition, hallucinations occur and delirium develops;
• manifestations of the nervous system: in some cases, headaches and dizziness/vertigo occur, as well as paresthesia with convulsions, syncope, dysgeusia, hypoesthesia or asthenia, a feeling of severe fatigue, insomnia or drowsiness. Occasionally, parosmia, anosmia, myasthenia gravis or ageusia develop;
• disturbances in the functioning of the visual organs: visual disturbances occasionally develop;
• manifestations from the auditory organs: tinnitus, deafness or hearing impairment occasionally occur. Often these problems developed during clinical trials with prolonged use of the drug in high doses. In general, such manifestations were curable;
• disturbances in the functioning of the cardiovascular system: tachycardia or arrhythmia (including ventricular tachycardia) occasionally appear. There have been isolated reports of prolongation of the QT interval, development of pirouette-type arrhythmia, decreased blood pressure, and ventricular fibrillation;
• Gastrointestinal manifestations: abdominal discomfort, nausea, diarrhea and vomiting often occur. Less common are bloating, loose stools, anorexia and gastritis with dyspepsia. Occasionally, the color of the tongue and teeth changes and constipation develops. Pancreatitis or pseudomembranous colitis have been observed in isolated cases;
• reactions of the hepatobiliary system: intrahepatic cholestasis or hepatitis occasionally developed (there were also reports of pathological changes in liver function test values). There were isolated reports of liver dysfunction and hepatitis in necrotic or fulminant form;
• infectious and invasive processes: candidiasis (also its oral form), vaginal pathologies, bacterial and fungal infections, as well as pneumonia, gastroenteritis, rhinitis with pharyngitis and respiratory dysfunction are rare;
• skin manifestations: allergic symptoms are rare, including itchy rash. Urticaria, photophobia and Quincke's edema occasionally develop. In addition, erythema multiforme and Stevens-Johnson/Lyell syndromes;
• disorders in the functioning of the muscular system and bones: sometimes joint pain appears;
• reactions from the urinary system: occasionally, acute renal failure, kidney pain, as well as dysuria and tubulointerstitial nephritis occur;
• disorders of the mammary glands and reproductive organs: sometimes uterine bleeding, vaginitis and testicular disorders occur;
• General reactions: sometimes anaphylaxis occurs, which includes chest pain and swelling;
• laboratory test results: often there is a decrease in the number of bicarbonates or lymphocytes, and also an increase in the level of eosinophils. Sometimes the urea indicator can increase, as well as creatinine with bilirubin in the plasma and the activity of the AST and ALT elements, and also the potassium indicator can change. All these disorders were reversible;
• intoxication processes and lesions: complications caused by the procedure.

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Overdose

Symptoms of drug overdose include severe diarrhea, vomiting and nausea, as well as treatable hearing loss.

Treatment of the disorder requires gastric lavage, as well as therapy aimed at maintaining the health of the victim and eliminating the signs of the disorder.

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Interactions with other drugs

Caution is required when combining azithromycin with other drugs that can prolong the QT interval (these are ketoconazole with lithium, and also quinidine with terfenadine, as well as cyclophosphamide with the substance haloperidol).

In the process of studying the interaction of the drug with antacids, no changes in the bioavailability of azithromycin were noted, although the peak level of the substance in the plasma was reduced by 25%. It is necessary to take azithromycin at least 1 hour before using antacids or 2 hours after.

Combined administration of the drug with cetirizine (at a dose of 20 mg) for a period of 5 days did not cause pharmacokinetic interactions at steady state, but significantly changed the QT interval values.

The combination of Azitro with ergot alkaloids or dihydroergotamine may provoke the development of a vasoconstrictor effect, accompanied by perfusion disorders, resulting in damage to the fingers and toes. For this reason, such combinations should be avoided.

When cimetidine was administered 2 hours before azithromycin administration, no changes were observed in the pharmacokinetic parameters of the latter.

Some macrolides can affect the process of cyclosporine metabolism. Because of this, when these agents are used in combination, it is necessary to constantly monitor cyclosporine levels and change the dose accordingly.

The combination of the drug with warfarin may enhance the anticoagulant effect, which is why it is necessary to monitor the PT indices during the treatment period.

There is information that macrolides are capable of affecting the intestinal metabolism of the substance digoxin, as a result of which, when using these drugs in combination, regular monitoring of digoxin levels is required.

The drug does not affect the pharmacokinetic parameters of theophylline in case of their combined use. However, the simultaneous administration of theophylline with other macrolides caused an increase in serum levels of this substance.

A single 1000 mg dose of zidovudine in combination with azithromycin (multiple doses of 600 or 1200 mg) did not affect the pharmacokinetic parameters or urinary excretion of zidovudine or its glucuronic breakdown products. However, azithromycin increased the levels of phosphorylated zidovudine within mononuclear cells in the peripheral bloodstream.

The combined use of Azithro with rifabutin had no effect on the plasma levels of these drugs. Neutropenia has developed in people who used these drugs simultaneously, but it should be noted that it was not possible to link the occurrence of this disorder to the use of azithromycin.

Taking it together with cisapride can increase prolongation of the QT interval, and also increase ventricular arrhythmia or fibrillation syndrome. For this reason, it is recommended not to combine these substances.

Combined use with alfentanil or astemizole should be done with caution, because increased exposure has been observed in combination with erythromycin.

Steady-state serum levels of azithromycin are increased when co-administered with nelfinavir. Although dosage adjustments are not recommended when combined with nelfinavir, careful monitoring for adverse effects of azithromycin is warranted.

It is necessary to keep in mind the possibility of developing cross-resistance between azithromycin, as well as other macrolides (eg, erythromycin) and clindamycin with lincomycin.

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Storage conditions

Azitro should be kept in a place inaccessible to small children. Temperature conditions for powder are no more than 30°C, but the ready-to-use suspension can be stored at no more than 25°C.

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Shelf life

Azitro is suitable for use for 3 years from the date of manufacture of the drug. At the same time, the finished suspension can be stored for a period of no more than 5 days.

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