Chemomycin, 100 mg/5 ml 11.43g

Pharmacotherapeutic group: Antibiotic, azalid

ATX CODE: [J01FA10]

Pharmacological properties

A broad spectrum antibiotic. It is a representative of a subgroup of macrolide antibiotics – azalides. At high concentrations it has a bactericidal effect.

The following Gram-positive bacteria are sensitive to azithromycin: Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, group C, F and O streptococci, Staphylococcus aureus, Streptococcus viridans; Gram-negative bacteria: Haemophilus influenzae, Moraxella catarrhalis, Bordetella pertussis, Bordetella parapertussis, Legionella pneumophila, Haemophilus ducreyi, Campylobacter jejuni, Neisseria gonorrhoeae and Gardnereila vaginalis; some anaerobic microorganisms: Bacleroides bivius, Clostridium perfringens, Peptostreptococcus spp; and Chlamydia trachomatis, Mycoplasma pneumoniae, Ureaplasma urealyticum, Treponema pallidum, Borrelia burgdorferi. Azithromycin is inactive against Gram-positive bacteria resistant to erythromycin.

Pharmacokinetics

Asithromycin is rapidly absorbed from the gastrointestinal tract due to its stability in acidic environment and lipophilicity. After oral administration of 500 mg, maximum blood plasma concentration of azithromycin is reached after 2.5-2.96 hours and is 0.4 mg/l. Bioavailability is 37%.

Asithromycin penetrates well into the respiratory tract, organs and tissues of the urogenital tract (in particular the prostate gland), skin and soft tissues. High tissue concentrations (10-50 times higher than in blood plasma) and long half-life are due to low binding of azithromycin to blood plasma proteins, as well as its ability to penetrate into eukaryotic cells and to concentrate in low pH environment surrounding lysosomes. This, in turn, determines a large apparent volume of distribution (31.1 L/kg) and high plasma clearance.

The ability of azithromycin to accumulate predominantly in lysosomes is particularly important for the elimination of intracellular pathogens. Phagocytes have been shown to deliver azithromycin to sites of infection where it is released during phagocytosis.

The concentration of azithromycin in the foci of infection is significantly higher than in healthy tissues (on average by 24-34%) and correlates with the degree of inflammatory edema. Despite its high concentration in phagocytes, azithromycin has no significant effect on their function. Azithromycin is maintained in bactericidal concentrations for 5-7 days after the last dose, which allowed to develop short (3-day and 5-day) courses of treatment.

It is demethylated in the liver; the resulting metabolites are inactive. Excretion of azithromycin from plasma is done in 2 stages: period of semi-elimination is 14-20 hours within 8-24 hours after drug intake and 41 hours – within 24-72 hours that allows using the preparation once daily. Food intake significantly changes pharmacokinetics (depending on the dosage form): suspension – Cmax increases (by 46%) and AUC (by 14%).

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to azithromycin:

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

– lower respiratory tract infections (bacterial and atypical pneumonia, acute bronchitis, exacerbation of chronic bronchitis);

– infections of the skin and soft tissues (acne vulgaris of moderate severity, erysipelas, impetigo, secondary infected dermatoses);

– infections of the urogenital tract (urethritis and/or cervicitis) caused by Chlamydia trachomatis;

– Lyme disease (borreliosis), for the treatment of the initial stage (erythema migrans).

Pharmacological effect

Pharmacotherapeutic group:
Antibiotic, azalide

ATX CODE: [J01FA10]

Pharmacological properties

Broad-spectrum antibiotic. It is a representative of the subgroup of macrolide antibiotics – azalides. In high concentrations it has a bactericidal effect.

Gram-positive cocci are sensitive to azithromycin: Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, streptococci of groups C, F and O, Staphylococcus aureus, Streptococcus viridans; gram-negative bacteria: Haemophilus influenzae, Moraxella catarrhalis, Bordetella pertussis, Bordetella parapertussis, Legionella pneumophila, Haemophilus ducreyi, Campylobacter jejuni, Neisseria gonorrhoeae and Gardnereila vaginalis; some anaerobic microorganisms: Bacleroides bivius, Clostridium perfringens, Peptostreptococcus spp; as well as Chlamydia trachomatis, Mycoplasma pneumoniae, Ureaplasma urealyticum, Treponema pallidum, Borrelia burgdorferi. Azithromycin is inactive against gram-positive bacteria resistant to erythromycin.

Pharmacokinetics

Azithromycin is rapidly absorbed from the gastrointestinal tract due to its stability in an acidic environment and lipophilicity. After oral administration of 500 mg, the maximum concentration of azithromycin in the blood plasma is reached after 2.5 – 2.96 hours and is 0.4 mg/l. Bioavailability is 37%.

Azithromycin penetrates well into the respiratory tract, organs and tissues of the urogenital tract (in particular the prostate gland), skin and soft tissues. The high concentration in tissues (10-50 times higher than in plasma) and the 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. This, in turn, determines the large apparent volume of distribution (31.1 l/kg) and high plasma clearance.

The ability of azithromycin to accumulate predominantly in lysosomes is especially important for the elimination of intracellular pathogens. It has been proven that phagocytes deliver azithromycin to sites of infection, where it is released during the process of phagocytosis.

The concentration of azithromycin in foci of infection is significantly higher than in healthy tissues (on average by 24-34%) and correlates with the degree of inflammatory edema. Despite its high concentration in phagocytes, azithromycin does not have a significant effect on their function. Azithromycin remains in bactericidal concentrations for 5-7 days after the last dose, which has made it possible to develop short (3-day and 5-day) courses of treatment.

It is demethylated in the liver, the resulting metabolites are not active. The elimination of azithromycin from blood plasma occurs in 2 stages: the half-life is 14-20 hours in the range from 8 to 24 hours after taking the drug and 41 hours in the range from 24 to 72 hours, which allows the drug to be used once a day. Food intake significantly changes pharmacokinetics (depending on the dosage form): suspension – Cmax increases (by 46%) and AUC (by 14%).

Special instructions

Hypersensitivity. As with erythromycin and other macrolides, rare cases of serious allergic reactions have been reported, including angioedema and anaphylaxis (rarely fatal), skin reactions including acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis (rarely fatal), drug rash with eosinophilia and systemic manifestations (DRESS syndrome). Some of these reactions that developed during the use of azithromycin acquired a recurrent course and required long-term treatment and observation.

If an allergic reaction develops, the drug should be discontinued and appropriate treatment should be started. It should be borne in mind that after discontinuation of symptomatic therapy, symptoms of an allergic reaction may resume.

If you miss 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.

Azithromycin should be taken at least one hour before or two hours after taking antacids.

Azithromycin should be used with caution in patients with mild to moderate hepatic impairment due to the possibility of developing fulminant hepatitis and severe liver failure.

If there are symptoms of liver dysfunction, such as rapidly increasing asthenia, jaundice, darkening of urine, tendency to bleeding, hepatic encephalopathy, drug therapy should be stopped and a study of the functional state of the liver should be performed.

For impaired renal function: in patients with GFR 10-80 ml/min, no dose adjustment is required; Therapy with Chemomycin should be carried out with caution and monitoring of renal function in patients with GFR less than 10 ml/min.

As with the use of other antibacterial drugs, during therapy with azithromycin, patients should be regularly examined for the presence of non-susceptible microorganisms and signs of the development of superinfections, including fungal ones.

The drug should not be used in longer courses than indicated in the instructions, since the pharmacokinetic properties of azithromycin allow us to recommend a short and simple dosage regimen.

There is no data on a possible interaction between azithromycin and ergotamine and dihydroergotamine derivatives, but due to the development of ergotism with the simultaneous use of macrolides with ergotamine and dihydroergotamine derivatives, this combination is not recommended.

With long-term use of azithromycin, the development of pseudomembranous colitis caused by Clostridium difficile, both in the form of mild diarrhea and severe colitis, is possible. If antibiotic-associated diarrhea develops while taking the drug, as well as 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded. You should not use medications that inhibit intestinal motility.

When treated with macrolides, including azithromycin, prolongation of cardiac repolarization and QT interval was observed, increasing the risk of developing cardiac arrhythmias, including torsade de pointes, which can lead to cardiac arrest.

Caution should be exercised when using the drug in patients with the presence of proarrhythmogenic factors (especially in elderly patients), including congenital or acquired prolongation of the QT interval; in patients receiving therapy with antiarrhythmic drugs of classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with water-electrolyte balance disorders, especially in the case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, cardiac arrhythmia or severe heart failure.

The use of azithromycin may provoke the development of myasthenic syndrome or cause an exacerbation of myasthenia gravis.

Impact on the ability to drive vehicles and operate machinery

Due to the possible development of undesirable reactions from the central nervous system and organ of vision during treatment, care must be taken when driving vehicles and performing other activities that require increased concentration and speed of psychomotor reactions.

Active ingredient

Azithromycin

Composition

5 ml of the finished suspension contains:

Active substance azithromycin (in the form of azithromycin dihydrate 104.809 mg) 100 mg,

Excipients:

Xanthan gum – 20.846 mg,

Sodium saccharinate – 4.134 mg,

Calcium carbonate – 162.503 mg,

Colloidal silicon dioxide – 26.008 mg,

Sodium phosphate anhydrous – 17.259 mg,

Sorbitol – 2145.682 mg,

Apple flavor – 3.303 mg,

Strawberry flavor – 8.159 mg,

Cherry flavor – 12.096 mg.

Pregnancy

During pregnancy, Chemomycin is prescribed only when the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

If it is necessary to use the drug during lactation, the issue of stopping breastfeeding while using the drug should be decided.

Contraindications

Hypersensitivity (including to other macrolides); liver and/or kidney failure; lactation period (suspended during treatment), children up to 6 months.

With caution – pregnancy, arrhythmia (possible ventricular arrhythmias and prolongation of the QT interval), children with severe impairment of liver or kidney function.

Side Effects

The frequency of side effects is classified in accordance with the recommendations of the World Health Organization: very often – at least 10%, often – at least 1%, but less than 10%, infrequently – at least 0.1%, but less than 1%, rarely – at least 0.01%, but less than 0.1%, very rarely – less than 0.01%; unknown frequency – cannot be estimated based on available data.

Infectious diseases: uncommon – candidiasis, including oral mucosa, vaginal infection, pneumonia, pharyngitis, gastroenteritis, respiratory diseases, rhinitis, fungal infection, bacterial infection; unknown frequency – pseudomembranous colitis.

From the blood and lymphatic system: infrequently – leukopenia, neutropenia, eosinophilia; very rarely – thrombocytopenia, hemolytic anemia.

From the side of metabolism and nutrition: infrequently – anorexia.

Allergic reactions: uncommon – angioedema, hypersensitivity reaction; unknown frequency – anaphylactic reaction.

From the nervous system: often – headache; infrequently – dizziness, disturbance of taste, paresthesia, drowsiness, insomnia, nervousness; rarely – agitation; unknown frequency – hypoesthesia, anxiety, aggression, fainting, convulsions, psychomotor hyperactivity, loss of smell, perverted sense of smell, loss of taste, myasthenia gravis, delirium, hallucinations.

From the side of the organ of vision: rarely – visual impairment.

From the organ of hearing and labyrinthine disorders: infrequently – hearing loss, vertigo; unknown frequency – hearing impairment, including deafness and/or tinnitus.

From the cardiovascular system: infrequently – a feeling of palpitations, “flushes” of blood to the face; unknown frequency – decreased blood pressure, increased QT interval on the electrocardiogram, pirouette-type arrhythmia, ventricular tachycardia.

From the respiratory system: infrequently – shortness of breath, nosebleeds.

From the gastrointestinal tract: very often – diarrhea; often – nausea, vomiting, abdominal pain; uncommon – flatulence, dyspepsia, constipation, gastritis, dysphagia, bloating, dry oral mucosa, belching, ulcers of the oral mucosa, increased secretion of the salivary glands; very rarely – change in tongue color, pancreatitis.

From the liver and biliary tract: infrequently – hepatitis; rarely – impaired liver function, cholestatic jaundice; unknown frequency – liver failure (in rare cases with death, mainly due to severe liver dysfunction); liver necrosis, fulminant hepatitis.

From the skin and subcutaneous tissues: infrequently – skin rash, itching, urticaria, dermatitis, dry skin, sweating; rarely – photosensitivity reaction, acute generalized exanthematous pustulosis; unknown frequency – Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug rash with eosinophilia and systemic manifestations (DRESS syndrome).

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

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

From the genital organs and mammary gland: infrequently – metrorrhagia, dysfunction of the testicles.

Other: infrequently – asthenia, malaise, feeling of fatigue, edema, facial swelling, chest pain, fever, peripheral edema.

Laboratory and instrumental 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 – increased activity of aspartate aminotransferase, alanine aminotransferase, increased concentration of bilirubin in the blood plasma, increased concentration of urea in the blood plasma, increased concentration of creatinine in the blood plasma, change in the potassium content in the blood plasma, increased activity of alkaline phosphatase in the blood plasma, increased chlorine content in the blood plasma, increased concentration of glucose in the blood, increased platelet count, decreased hematocrit, increased concentration of bicarbonates in the blood plasma, change in sodium content in blood plasma.

Interaction

Antacids

Antacids do not affect the bioavailability of azithromycin, but reduce the maximum blood concentration by 30%, so the drug should be taken at least one hour before or two hours after taking these drugs and eating.

Cetirizine

Concomitant use of azithromycin with cetirizine (20 mg) for 5 days in healthy volunteers did not lead to pharmacokinetic interaction or 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 to the placebo group.

Digoxin and colchicine (P-glycoprotein substrates)

Concomitant use of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates, such as digoxin and colchicine, leads to increased concentrations of P-glycoprotein substrate in the blood serum. Thus, with the simultaneous use of azithromycin and digoxin, it is necessary to take into account the possibility of increasing digoxin in the blood serum.

Zidovudine

Concomitant use of azithromycin (single dose of 1000 mg and multiple doses of 1200 mg or 600 mg) has little effect on the pharmacokinetics, including 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 interacts weakly with isoenzymes of the cytochrome P450 system. Azithromycin has not been shown to participate in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin is not an inhibitor or inducer of cytochrome P450 isoenzymes.

Ergot alkaloids

Given the theoretical possibility of ergotism, the simultaneous use of azithromycin with ergot alkaloid derivatives is not recommended.

Pharmacokinetic studies were conducted on the simultaneous use of azithromycin and drugs whose metabolism occurs with the participation of isoenzymes of the cytochrome P450 system.

Atorvastatin

Concomitant use of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause changes in atorvastatin plasma concentrations (based on an HMC-CoA reductase inhibition assay). However, in the post-marketing period, isolated case reports of rhabdomyolysis have been received in patients receiving concomitant azithromycin and statins.

Carbamazepine

Pharmacokinetic studies involving healthy volunteers did not reveal a significant effect on the plasma concentrations of carbamazepine and its active metabolite in patients receiving concomitant azithromycin.

Cimetidine

In pharmacokinetic studies of the effect of a single dose of cimetidine on the pharmacokinetics of azithromycin, no changes in the pharmacokinetics of azithromycin were detected when cimetidine was used 2 hours before azithromycin.

Indirect anticoagulants (coumarin derivatives)

In pharmacokinetic studies, azithromycin did not affect the anticoagulant effect of a single 15 mg dose of warfarin administered to healthy volunteers. Potentiation of the anticoagulant effect has been reported after simultaneous use of azithromycin and indirect anticoagulants (coumarin derivatives). Although a causal relationship has not been established, the need for frequent monitoring of prothrombin time should be considered when using azithromycin in patients receiving indirect oral anticoagulants (coumarin derivatives).

Cyclosporine

In a pharmacokinetic study involving healthy volunteers who took azithromycin (500 mg/day once) orally for 3 days, followed by cyclosporine (10 mg/kg/day once), a significant increase in the maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-5) of cyclosporine was detected. Caution is advised when using these drugs together. If simultaneous use of these drugs is necessary, it is necessary to monitor the concentration of cyclosporine in the blood plasma and adjust the dose accordingly.

Efavirenz

Concomitant 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

Concomitant use of azithromycin (1200 mg once) did not change the pharmacokinetics of fluconazole (800 mg once). The total exposure and half-life of azithromycin did not change with simultaneous use of fluconazole, however, a decrease in Cmax of azithromycin was observed (by 18%), which had no clinical significance.

Indinavir

Concomitant use of azithromycin (1200 mg once) did not cause a statistically significant effect on the pharmacokinetics of indinavir (800 mg three times a day for 5 days).

Methylprednisolone

Azithromycin does not have a significant effect on the pharmacokinetics of methylprednisolone.

Nelfinavir

The simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times a day) causes an increase in the equilibrium concentrations of azithromycin in the blood serum. No clinically significant side effects were observed and no dose adjustment of azithromycin was required when used concomitantly with nelfinavir.

Rifabutin

The simultaneous use of azithromycin and rifabutin does not affect the concentration of each drug in the blood serum. Neutropenia has sometimes been observed with simultaneous use of azithromycin and rifabutin. 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 daily for 3 days) on the AUC and Cmax of sildenafil or its main circulating metabolite.

Terfenadine

In pharmacokinetic studies, there was no evidence of interaction between azithromycin and terfenadine. There have been isolated cases reported where the possibility of such an interaction could not be completely excluded, but there was no concrete evidence that such an interaction occurred.

It has been found that the simultaneous use of terfenadine and macrolides can cause arrhythmia and prolongation of the QT interval.

Theophylline

No interaction has been detected between azithromycin and theophylline.

Triazolam/midazolam

No significant changes in pharmacokinetic parameters were detected with simultaneous use of azithromycin with triazolam or midazolam in therapeutic doses.

Trimethoprim/sulfamethoxazole

Concomitant use of trimethoprim/sulfamethoxazole with azithromycin did not show a significant effect on Cmax, total exposure or renal excretion of trimethoprim or sulfamethoxazole. Azithromycin serum concentrations were consistent with those found in other studies.

Overdose

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

Treatment: symptomatic.

Prescribing

Antibiotic azalide

Complete set of goods

Powder for the preparation of suspension for oral administration 100 mg/5 ml. 11.43 g of powder in a dark glass bottle with a capacity of 60 ml, sealed with a screw-on, tamper-evident plastic or metal cap.

On the top side of the plastic cap there is a diagram for opening the bottle.
The bottle along with a measuring spoon (volume 5 ml, with a line for a volume of 2.5 ml) and instructions for use are placed in a cardboard box.

Functional features

Azithromycin is rapidly absorbed from the gastrointestinal tract, due to its stability in an acidic environment and lipophilicity.

After oral administration of 500 mg, the maximum concentration of azithromycin in the blood plasma is reached after 2.5 – 2.96 hours and is 0.4 mg/l. Bioavailability is 37%.

Azithromycin penetrates well into the respiratory tract, organs and tissues of the urogenital tract (in particular the prostate gland), skin and soft tissues.

The high concentration in tissues (10-50 times higher than in plasma) and the 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.

This, in turn, determines the large apparent volume of distribution (31.1 l/kg) and high plasma clearance.

The ability of azithromycin to accumulate predominantly in lysosomes is especially important for the elimination of intracellular pathogens.

It has been proven that phagocytes deliver azithromycin to sites of infection, where it is released during the process of phagocytosis.

The concentration of azithromycin in foci of infection is significantly higher than in healthy tissues (on average by 24-34%) and correlates with the degree of inflammatory edema.

Despite its high concentration in phagocytes, azithromycin does not have a significant effect on their function.

Azithromycin remains in bactericidal concentrations for 5-7 days after the last dose, which made it possible to develop short (3-day and 5-day) courses of treatment.

It is demethylated in the liver, the resulting metabolites are not active.

Azithromycin has a very long half-life – 35-50 hours. The half-life from tissues is much longer. Azithromycin is excreted mainly unchanged – 50% by the intestines, 6% by the kidneys.

Storage conditions

Store in a dry place, protected from light, at a temperature of 15 to 25 °C.

Keep out of the reach of children.

Shelf life

3 years. Do not use after the expiration date stated on the package.

Manufacturer

Hemofarm A.D., Serbia