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 (moderate acne vulgaris, rye, impetigo, secondary infected dermatoses);

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

– Lyme disease (borreliosis), to treat the initial stage (erythema migrans).

Active ingredient

Composition

5 ml of the ready-to-use suspension contains:

The active ingredient azithromycin (in the form of azithromycin dihydrate 104.809 mg) 100 mg,

The excipients:

Xanthan gum – 20.846 mg,

Sodium saccharinate – 4.134 mg,

Calcium carbonate – 162.503 mg,

Silicon dioxide colloid – 26.008 mg,

Anhydrous sodium phosphate – 17.259 mg,

Sorbitol – 2145.682 mg,

Apple flavoring – 3.303 mg,

Strawberry flavoring – 8.159 mg,

Cherry flavoring – 12.096 mg.

How to take, the dosage

The drug is taken orally 1 time/day 1 hour before a meal or 2 hours after a meal.

The bottle is gradually filled with water (distilled or boiled and cooled) up to the mark.

The contents of the bottle are shaken thoroughly until a homogeneous suspension is obtained.

If the level of the slurry prepared is below the label mark on the bottle, add water to the mark and shake again.

The prepared suspension is stable at room temperature for 5 days.

Infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues (except for erythema migrans)

In children: at the rate of 10 mg/kg body weight once a day for 3 days (the course dose is 30 mg/kg). Depending on the body weight of the child the following dosing regimen is recommended:

In pharyngitis/tonsillitis caused by Streptococcus pyogenes, azithromycin is used in a dose of 20 mg/kg/day for 3 days (course dose of 60 mg/kg). The maximum daily dose is 500 mg.

Adults: 500 mg (25 ml of 100 mg/5 ml suspension) once daily for 3 days (course dose of 1.5 g).

In Lyme disease (borreliosis) to treat the initial stage (erythema migrans) – once a day for 5 days: on the 1st day in a dose of 20 mg/kg body weight, and then from the 2nd to the 5th day – 10 mg/kg body weight (course dose 60 mg/kg).

The following dosing regimen of Chemomycin suspension in children with erythema migrans is recommended:

The suspension should be shaken before use.

In the immediate aftermath of taking the suspension, the child should be given a few sips of fluid (water, tea) to wash off and swallow the residual suspension in the mouth.

If a dose of the drug is missed, it should be taken immediately, if possible, and then subsequent doses taken 24 hours apart.

Patients with impaired renal function: In patients with a GFR of 10-80 ml/min, no dose adjustment is necessary.

Patients with hepatic impairment: No dose adjustment is necessary when used in patients with mild to moderate hepatic impairment.

Elderly patients: No dose adjustment is required. In elderly patients with azithromycin special caution is recommended due to possible presence of proarrhythmogenic factors which may increase the risk of cardiac arrhythmia and pirouette arrhythmia.

Interaction

The antacids do not affect the bioavailability of azithromycin, but decrease the maximum blood concentration by 30%; therefore, the drug should be taken at least one hour before or two hours after taking these drugs and meals.

Cetirizine

Concomitant use for 5 days in healthy volunteers of azithromycin with cetirizine (20 mg) did not result in a pharmacokinetic interaction or significant change in the QT interval.

Didanosine (didezoxynosine)

The concomitant use of azithromycin (1200 mg/day) and didanosine (400 mg/day) in 6 HIV-infected patients showed no change in the pharmacokinetic parameters of didanosine compared with the placebo group.

Digoxin and colchicine (P-glycoprotein substrates)

The concomitant use of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates such as digoxin and colchicine results in higher serum P-glycoprotein substrate concentrations. Thus, when concomitant use of azithromycin and digoxin is necessary to consider the possibility of increasing digoxin in the blood serum.

Zidovudine

The concomitant use of azithromycin (single administration of 1000 mg and multiple administration of 1200 mg or 600 mg) has little effect on the pharmacokinetics, including renal excretion, of zidovudine or its glucuronide metabolite. However, azithromycin administration caused an increase in the concentration of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of this fact is unclear.

Azithromycin interacts weakly with cytochrome P450 isoenzymes. Azithromycin has not been found to be involved in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin is not an inhibitor and inducer of cytochrome P450 isoenzymes.

According to the theoretical possibility of ergotism, concomitant use of azithromycin with ergot alkaloid derivatives is not recommended.

Pharmacokinetic studies have been performed on the concomitant use of azithromycin and drugs metabolized by cytochrome P450 isoenzymes.

Atorvastatin

Concomitant use of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause changes in plasma concentrations of atorvastatin (on the basis of HMK-CoA reductase inhibition assay). However, in the post-registration period there were isolated reports of cases of rhabdomyolysis in patients receiving azithromycin and statins simultaneously.

Carbamazepine

Pharmacokinetic studies with healthy volunteers showed no significant effect on plasma concentrations of carbamazepine and its active metabolite in patients receiving azithromycin concomitantly.

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 found, provided that cimetidine was used 2 hours before azithromycin.

Indirect anticoagulants (coumarin derivatives)

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

Cyclosporine

. In a pharmacokinetic study involving healthy volunteers who received oral azithromycin (500 mg/day once daily) for 3 days followed by cyclosporine (10 mg/kg/day once daily), a significant increase in maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC0-5) of cyclosporine was found. Caution should be exercised when concomitant use of these drugs. In case of necessity of concomitant use of these drugs, it is necessary to monitor plasma concentrations of cyclosporine and adjust the dose accordingly.

Efavirenz

The concomitant use of azithromycin (600 mg/day once daily) 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 daily) did not alter the pharmacokinetics of fluconazole (800 mg once daily). The total exposure and half-life of azithromycin were not altered by concomitant use of fluconazole, but there was a decrease in Cmax of azithromycin (by 18%), which had no clinical significance.

Indinavir

The concomitant use of azithromycin (1200 mg once) had no statistically significant effect on the pharmacokinetics of indinavir (800 mg three times daily for 5 days).

Methylprednisolone

Asithromycin has no significant effect on the pharmacokinetics of methylprednisolone.

Nelfinavir

The simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times daily) causes increased equilibrium serum concentrations of azithromycin. No clinically significant adverse effects have been observed and no dose adjustment of azithromycin is required when used concomitantly with nelfinavir.

Rifabutin

The concomitant use of azithromycin and rifabutin has no effect on the serum concentrations of either drug. Neutropenia was sometimes observed when azithromycin and rifabutin were used concomitantly. Although neutropenia has been associated with the use of rifabutin, a causal relationship between the use of a combination of azithromycin and rifabutin and neutropenia has not been established.

Sildenafil

There is no evidence of an effect of azithromycin (500 mg/day daily for 3 days) on the AUC and Cmax of sildenafil or its major circulating metabolite when used in healthy volunteers.

Terfenadine

In pharmacokinetic studies there has been no evidence of interaction between azithromycin and terfenadine. There have been isolated cases reported in which the possibility of such an interaction could not be completely ruled out, but there has not been any concrete evidence that this interaction has occurred.

The concomitant use of terfenadine and macrolides has been found to cause arrhythmias and prolongation of the QT interval.

Theophylline

No interaction between azithromycin and theophylline has been identified.

Triazolam/midazolam

There are no significant changes in pharmacokinetic parameters when azithromycin is used concomitantly with triazolam or midazolam in therapeutic doses.

Trimethoprim/sulfamethoxazole

The concomitant use of trimethoprim/sulfamethoxazole with azithromycin showed 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.

Special Instructions

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

If a dose of the drug is missed, the missed dose should be taken as soon as possible, and the subsequent doses should be taken 24 hours apart.

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

Asithromycin should be used with caution in patients with mild to moderate hepatic impairment because of the possibility of fulminant hepatitis and severe hepatic failure.

In case of symptoms of hepatic impairment, such as rapidly increasing asthenia, jaundice, darkened urine, bleeding tendency, hepatic encephalopathy, the drug therapy should be discontinued and liver function testing should be performed.

In patients with renal dysfunction: in patients with a GFR of 10-80 ml/min, no dose adjustment is required; the drug therapy with Chemomycin should be used with caution while monitoring renal function in patients with a GFR less than 10 ml/min.

As with other antibacterial agents, azithromycin therapy should routinely screen patients for the presence of non-susceptible microorganisms and signs of superinfections, including fungal infections.

The drug should not be used for longer courses than indicated, since the pharmacokinetic properties of azithromycin recommend a short and simple dosing regimen.

There are no data on possible interaction between azithromycin and derivatives of ergotamine and dihydroergotamine, but because of the development of ergotism when using macrolides with derivatives of ergotamine and dihydroergotamine simultaneously, this combination is not recommended.

The development of pseudomembranous colitis caused by Clostridium difficile is possible with long-term administration of azithromycin, both as mild diarrhea and severe colitis. If antibiotic-associated diarrhea develops against the background of the drug, as well as 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded. Do not use drugs that inhibit intestinal peristalsis.

In treatment with macrolides, including azithromycin, prolongation of cardiac repolarization and QT interval have been observed, increasing the risk of cardiac arrhythmias, including pirouette arrhythmias, which may lead to cardiac arrest.

Cautions should be taken 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 disorders of fluid and electrolyte balance, especially in case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, cardiac arrhythmia or severe heart failure.

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

We should be careful when driving vehicles and performing other activities requiring high concentration and rapid psychomotor reaction times due to possible development of adverse reactions of central nervous system and eyesight during the treatment.

Synopsis

Features

Contraindications

Side effects

The frequency of side effects is classified in accordance with the recommendations of the World Health Organization: very frequently – at least 10%; frequently – 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: infrequent – candidiasis, including oral mucosa, vaginal infection, pneumonia, pharyngitis, gastroenteritis, respiratory diseases, rhinitis, fungal infection, bacterial infection; unknown frequency – pseudomembranous colitis.

Blood and lymphatic system disorders: infrequent leukopenia, neutropenia, eosinophilia; very rare – thrombocytopenia, hemolytic anemia.

Metabolism and nutrition: infrequent – anorexia.

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

Nervous system disorders: frequent – headache; infrequent – dizziness, impaired sense of taste, paresthesias, somnolence, insomnia, nervousness; rare – agitation; unknown frequency – hypoesthesia, anxiety, aggression, fainting, seizures, psychomotor hyperactivity, loss of smell, perverse sense of smell, loss of taste, myasthenia, delirium, hallucinations.

Visual organ disorders:infrequent – visual impairment.

Hearing organ and labyrinth disorders: infrequent – hearing disorder, vertigo; unknown frequency – hearing disorder, including deafness and/or tinnitus.

Cardiovascular system: infrequent – feeling of palpitations, “rushes” of blood to the face; unknown frequency – decreased blood pressure, increased QT interval on electrocardiogram, arrhythmia type “pirouette”, ventricular tachycardia.

Respiratory system disorders: infrequent – dyspnea, nasal bleeding.

Gastro-intestinal tract: very frequently – diarrhea; frequently – nausea, vomiting, abdominal pain; infrequently – flatulence, dyspepsia, constipation, gastritis, dysphagia, bloating, dry oral mucosa, belching, oral mucosa ulcers, increased salivary gland secretion; very rarely – discoloration of the tongue, pancreatitis.

Hepatic and biliary tract disorders: infrequent – hepatitis; rare – liver dysfunction, cholestatic jaundice; unknown frequency – liver failure (in rare cases with fatal outcome mainly due to severe liver failure); liver necrosis, fulminant hepatitis.

Skin and subcutaneous tissue disorders: infrequent – skin rash, itching, urticaria, dermatitis, dry skin, sweating; rare – photosensitization reaction, acute generalized exanthematous pustulosis; unknown frequency – Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug rash with eosinophilia and systemic manifestations (DRESS syndrome).

Musculoskeletal system: infrequent osteoarthritis, myalgia, back pain, neck pain; unknown frequency – arthralgia.

Renal and urinary tract: infrequent dysuria, pain in the kidney; unknown frequency – interstitial nephritis, acute renal failure.

Gender and mammary gland disorders: infrequent – metrorrhagia, impaired testicular function.

Others: infrequent – asthenia, malaise, feeling of fatigue, edema, facial edema, chest pain, fever, peripheral edema.

Laboratory and instrumental findings: frequent – decreased lymphocyte count, increased eosinophil count, increased basophil count, increased monocyte count, increased neutrophil count, decreased plasma bicarbonate concentration; infrequent – increased activity of aspartate aminotransferase, alanine aminotransferase, increased concentration of bilirubin in blood plasma, increased concentration of urea in blood plasma, increased concentration of creatinine in blood plasma, changes in plasma potassium, increased plasma alkaline phosphatase activity, increased plasma chloride concentration, increased blood glucose concentration, increased platelet count, decreased hematocrit, increased plasma bicarbonate concentration, change in plasma sodium concentration.

Overdose

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

Treatment: symptomatic.

Pregnancy use

In pregnancy Chemomycin is administered only when the expected benefit of therapy for the mother exceeds the potential risk to the fetus.

If it is necessary to use the drug during lactation, discontinuation of breastfeeding should be considered.

Similarities