AzitRus, 200 mg 4.2g 3 pcs.

According to the FDA (2020), oral azithromycin is indicated for the treatment of patients with mild to moderate infections (pneumonia: see “Precautions”) caused by susceptible strains of the indicated microorganisms under certain conditions listed below.

Adults

Acute bacterial exacerbations of chronic obstructive pulmonary disease caused by Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.

Acute bacterial sinusitis caused by Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.

Out-of-hospital pneumonia caused by Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae in patients who are prescribed oral therapy.

. Azithromycin should not be used in patients with pneumonia who are not indicated for oral therapy because of moderate to severe disease or when risk factors are present, such as patients with cystic fibrosis, patients with nosocomial infections, patients with known or suspected bacteremia, patients requiring hospitalization, elderly or frail patients, patients with serious underlying health problems that may impede their ability to respond to disease (including immunodeficiency or functional

Pharyngitis/tonsillitis caused by Streptococcus pyogenes is an alternative to first-line therapy in patients in whom first-line therapy cannot be used.

Note. Penicillin administered by injection/m is usually the drug of choice in the treatment of infections caused by Streptococcus pyogenes and the prevention of rheumatic fever. Azithromycin is often effective in eradicating sensitive strains of Streptococcus pyogenes from the nasopharynx. Since some strains are resistant to azithromycin, tests for azithromycin sensitivity should be performed during treatment of patients. There are no data confirming the effectiveness of azithromycin in the subsequent prevention of rheumatic fever.

Uncomplicated infections of the skin and skin structures caused by Staphylococcus aureus, Streptococcus pyogenes or Streptococcus agalactiae. Abscesses usually require surgical intervention.

Urethritis and cervicitis caused by Chlamydia trachomatis or Neisseria gonorrhoeae.

Infectious genital disease in men caused by Haemophilus ducreyi (Chancroid). Because of the small number of women included in clinical trials, the effectiveness of azithromycin in the treatment of chancroid in women has not been established.

Azithromycin should not be relied on at the recommended dose to treat syphilis. Antimicrobials used in high doses for short periods of time to treat nongonococcal urethritis may mask or delay the presentation of symptoms during the incubation period of syphilis. All patients with urethritis or cervicitis as a result of a sexually transmitted infection should have a serologic test for syphilis and appropriate cultures for gonorrhea at the time of diagnosis. If the infection is confirmed, appropriate antimicrobial therapy should be started and follow-up tests for these diseases should be performed.

At the beginning of treatment, appropriate tests should be performed to determine the pathogen and its sensitivity to azithromycin. Azithromycin therapy may be initiated before the results of these tests are available; once the results are available, antimicrobial therapy should be adjusted.

In order to prevent the development of drug-resistant bacteria and to maintain the effectiveness of azithromycin and other antibacterial drugs, azithromycin should only be used to treat or prevent infections for which sensitive bacteria are proven or reasonably suspected to cause them. When culture and sensitivity information is available, it should be considered when selecting or modifying antibiotic therapy. In the absence of such data, the local epidemiologic situation and sensitivity patterns may contribute to the empirical choice of therapy.

Pediatric patients

Acute otitis media caused by Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.

Out-of-hospital pneumonia caused by Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae in patients who are indicated for oral therapy.

. Azithromycin should not be used in pediatric patients with pneumonia who are not indicated for oral therapy because of moderate to severe disease or when risk factors are present, such as patients with cystic fibrosis, patients with hospital-acquired infections, patients with known or suspected bacteremia, patients requiring hospitalization, patients with serious underlying health problems that may impede the ability to respond to disease (including immune deficiency or functional asperity).

Pharyngitis/tonsillitis caused by Streptococcus pyogenes is an alternative to first-line therapy in patients in whom first-line therapy cannot be used.

Note. Penicillin administered by injection/m is usually the drug of choice in the treatment of infections caused by Streptococcus pyogenes and the prevention of rheumatic fever. Azithromycin is often effective in eradicating sensitive strains of Streptococcus pyogenes from the nasopharynx. Since some strains are resistant to azithromycin, tests for azithromycin sensitivity should be performed during treatment of patients. There are no data confirming the efficacy of azithromycin in the subsequent prevention of rheumatic fever.

At the beginning of treatment, appropriate tests should be performed to determine the causative agent and its sensitivity to azithromycin. Azithromycin therapy may be initiated before the results of these tests are available; once the results are available, antimicrobial therapy should be adjusted.

Active ingredient

Composition

1 package contains:

azithromycin (in the form of dihydrate) 200 mg;

excipients:

sodium citrate (sodium citric acid tri-substituted),

orange food flavoring,

How to take, the dosage

Orally 1 hour before a meal or 2 hours after a meal once a day.

In adults:

Infections of the upper and lower respiratory tract 500 mg/day at 1 dose for 3 days (course dose 15 g).

Infections of the skin and soft tissues: 500 mg/d at 1 dose for 3 days (15 g course dose).

In acute infections of the urogenital organs (uncomplicated urethritis or cervicitis) 1 g once.

In Lyme disease (borreliosis) to treat stage I (erythema migrans) 1 g on the first day and 500 mg daily from days 2 to 5 (course dose of 3 g).

In children from 6 months:

Infections of upper and lower respiratory tract ENT organs, skin and soft tissues (except for erythema migrans) are indicated in a single (daily) dose of 10 mg/kg body weight once daily for 3 consecutive days (the course dose is 30 mg/kg body weight).

In case of pharyngitis and tonsillitis caused by Streptococcus pyogenes the preparation AzitRUS® is used in dose 20 mg/kg/day during 3 days (course dose – 60 mg/kg). The maximum daily dose is 500 mg.

In case of Lyme disease (initial stage of Borreliosis) erythema migrans the drug is indicated in children once a day for 5 days: 20 mg/kg body weight during the first day and 10 mg/kg body weight during days 2 to 5 (course dose 60 mg/kg).

Note:

The dose of 150 mg corresponds to: 1 package 100 mg – 1 package 50 mg or 3 packages 50 mg:

The dose of 250 mg corresponds to: 1 package 200 mg + 1 package 50 mg or 2 packages 100 mg – 1 package 50 mg;

dose 500 mg corresponds to: 1 package 200 mg + 1 package 100 mg or 3 packages 100 mg; dose 400 mg corresponds to: 2 bags 200 mg or 4 bags 100 mg or 8 bags 50 mg or 3 bags 100 mg + 2 bags 50 mg or 2 bags 100 mg – 4 bags 50 mg;

dose 500 mg corresponds to: 2 bags 200 mg+1 bag 100 mg or 5 bags 100 mg or 1 bag 200 mg + 3 bags 100 mg or 2 bags 100 mg + 6 bags 50 mg or 10 bags 50 mg.

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

Patients with impaired renal function

In patients with impaired renal function (CKR greater than 40 ml min), no dose adjustment is required.

Patients with hepatic impairment and elderly patients

Dose adjustment is not required when used in patients with mild to moderate hepatic impairment in elderly patients.

Preparation method.

In a clean beaker boiled and cooled to room temperature water is added in an amount not less than 10 ml (2 teaspoons) per one bag of the preparation, then the contents of one or more bags are poured and stirred until a homogeneous suspension is obtained.

After intake, rinse the cup with water dry and store it in a dry and clean place.

Interaction

Antacids do not affect bioavailability of azithromycin but decrease maximum blood plasma concentrations by 30%; therefore, azithromycin should be taken at least one hour before or two hours after taking these drugs. Azithromycin does not affect plasma concentrations of carbamazepine cimetidine didanosine efavirenz fluconazole indinavir midazolam theophylline triazolam trimethoprim/sulfamethoxazole cetirizine sildenafil atorvastatin rifabutin and methylprednisolone during concomitant use.

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

There have been isolated reports of rhabdomyolysis in patients receiving azithromycin and statins concomitantly.

In concomitant use of azithromycin and rifabutin, neutropenia has occasionally been observed, although neutropenia has been associated with rifabutin use, a causal relationship between azithromycin and rifabutin combination use and neutropenia has not been established.

In case of concomitant use of azithromycin and cyclosporine, correction of the dose of cyclosporine is necessary.

Asithromycin 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 neither an inhibitor nor an inducer of cytochrome P450 isoenzymes.

In concomitant use of digoxin and azithromycin it is necessary to monitor the concentration of digoxin in blood plasma since many macrolides increase digoxin absorption in the intestine.

When concomitant use with indirect anticoagulants (warfarin other coumarin-type anticoagulants) is necessary, close monitoring of prothrombin time is recommended.

The concomitant use of terfenadine and macrolide class antibiotics has been shown to cause arrhythmias and prolongation of QT interval. Therefore this complication cannot be excluded when terfenadine and azithromycin are taken concomitantly.

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

In concomitant use with zidovudine azithromycin has no effect on the pharmacokinetic parameters of zidovudine in blood plasma or on the renal excretion of it and its metabolite glucuronide. However, the concentration of the active metabolite phosphorylated zidovudine in mononuclear cells of peripheral vessels is increased. The clinical significance of this fact is not clear.

Special Instructions

When prescribing AzitRus® in patients with diabetes as well as in patients on a low-calorie diet it should be taken into account that the drug contains sucrose (about 03 XE in one packet).

If a dose of AzitRUS® is missed, take the missed dose as soon as possible and the next ones at 24-hour intervals.

AzitRUS® should be used with caution in patients with mild hepatic impairment due to possible development of fulminant hepatitis and severe hepatic failure.

In case of symptoms of liver dysfunction such as rapidly increasing asthenia jaundice darkening of urine bleeding tendency hepatic encephalopathy therapy with AzitRUS® should be stopped and liver function tests should be performed.

In case of renal dysfunction of mild degree of severity (CK values over 40 ml/min) the treatment with azitRUS® should be used with caution and with monitoring of renal function.

We should remember that for the prevention of pharyngitis/tonsillitis caused by Streptococcuspyogenes and for the prevention of acute rheumatic fever the drug of choice is usually penicillin.

As with other antibacterials, during therapy with AzitRUS® patients should be routinely screened for the presence of non-susceptible microorganisms and signs of superinfections, including fungal ones.

AzitRus® should not be used for longer courses than directed since the pharmacokinetic properties of azithromycin allow for a short and convenient dosing regimen.

There are no data on possible interaction between azithromycin and ergotamine and dihydroergotamine derivatives but due to the development of argotism when using macrolides with ergotamine and dihydroergotamine derivatives simultaneously this combination is contraindicated. When prolonged use of AzizRUS®, development of pseudomembranous colitis caused by Clostridium difficile both as mild diarrhea and as severe colitis is possible. If diarrhea develops during azithromycin therapy and also 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded. Drugs inhibiting intestinal peristalsis are contraindicated.

Delayed ventricular repolarization syndrome, prolonged QT interval syndrome increases the risk of arrhythmias including “pirouette” type arrhythmias during macrolide therapy and with the use of AzitRUS®. Caution should be observed when using AzitRUS® in patients with the presence of proarrhythmogenic factors (especially in elderly patients): with congenital or acquired prolongation of QT interval in patients receiving therapy with antiarrhythmic drugs of class IA (quinidine procainamide) III (dofetilide amiodarone and sotalol) cisapride terfenadine antipsychotic drugs (pimozide) antidepressants (citalopram) fluoroquinolones (moxifloxacin and levofloxacin) in patients with disorders of water andelectrolyte balance disorders especially in cases of hypokalemia or hypomagnesemia with clinically significant bradycardia, cardiac arrhythmia or severe heart failure.

The use of AzitRUS® may provoke development of myasthenic syndrome or cause exacerbation of myasthenia gravis.

When the nervous system and eyesight show adverse effects, caution should be exercised while performing activities requiring high concentration and rapid psychomotor reaction.

Contraindications

Side effects

In clinical trials, most side effects reported were mild to moderate in severity and reversible after azithromycin withdrawal. Potentially serious side effects, such as angioneurotic edema and cholestatic jaundice, were rarely reported. Approximately 0.7% of patients (adults and children) in 5-day multiple-dose clinical trials discontinued azithromycin therapy because of the development of treatment-related side effects.

In adults who received azithromycin at a dose of 500 mg/day, the rate of discontinuation due to treatment-related side effects after 3 days of treatment was 0.6%. In clinical trials involving pediatric patients, when 30 mg/kg was administered either as a single dose of azithromycin or for 3 days, discontinuation of azithromycin associated with the development of treatment-associated side effects was about 1%. Most side effects leading to discontinuation were GI-related, including nausea, vomiting, diarrhea, or abdominal pain.

The results of clinical trials

Because clinical trials are conducted with a different set of conditions, the incidence of adverse reactions observed in these clinical trials may not match that obtained in other clinical trials and observed in clinical practice.

Adults

Multidose regimens. Overall, the most common treatment-associated adverse reactions in adult patients receiving multiple doses of azithromycin were gastrointestinal effects. The most commonly reported adverse reactions were diarrhea/ fluid stools (4-5%), nausea (3%), and abdominal pain (2-3%).

There were no other treatment-related adverse effects with an incidence greater than 1% in patients receiving multiple doses of azithromycin.

The undesirable reactions that occurred with a frequency of ≤1% included the following.

Cardiovascular side: palpitations, chest pain.

Gastrointestinal disorders: dyspepsia, flatulence, vomiting, melena, cholestatic jaundice.

Urinary system: candidiasis, vaginitis, nephritis.

Nervous system disorders: dizziness, headache, vertigo, drowsiness.

General: fatigue.

Allergic reactions: rash, skin itching, photosensitivity, angioedema.

The single dose regimen is 1 g. In general, the most frequent adverse effects in patients who received azithromycin single dose 1 g were gastrointestinal related and were reported more frequently than in patients who received the multiple-dose regimen.

The side effects reported in patients receiving single-dose azithromycin with a frequency of 1% or more included diarrhea/iodine stool (7%), nausea (5%), abdominal pain (5%), vomiting (2%), dyspepsia (1%), vaginitis (1%).

The single dose regimen is 2 g. Overall, the most frequent side effects in patients who received azithromycin in a single dose of 2 g were gastrointestinal related.

The side effects reported in patients on a single dose of azithromycin in this study with a frequency of 1% or more included nausea (18%), diarrhea/ fluid stools (14%), vomiting (7%), abdominal pain (7%), vaginitis (2%), dyspepsia (1%), and dizziness (1%). Most complaints were moderate in nature.

Pediatric patients

Single- and multiple-dose regimens. The types of side effects in pediatric patients were comparable to those in adults, with different frequencies for the dosing regimens recommended in pediatric practice.

Acute otitis media: at the recommended total dosage of 30 mg/kg, the most frequent treatment-related side effects (≥1%) were diarrhea, abdominal pain, vomiting, nausea, and rash.

The frequency of side effects, depending on dosing regimen, for 1-, 3-, and 5-day dosing regimens were: diarrhea, 4.3; 2.6 and 1.8%; abdominal pain, 1.4; 1.7 and 1.2%; vomiting, 4.9; 2.3 and 1.1%; nausea, 1, 0.4 and 0.5%; rash, 1, 0.6 and 0.4%.

Out-of-hospital pneumonia: for the recommended dosing regimen of 10 mg/kg on day 1 followed by 5 mg/kg on days 2-5, the most common treatment-related adverse events were diarrhea/ladder stool (5.8%), abdominal pain (1.9%), vomiting (1.9%), nausea (1.9%), and rash (1.6%).

Pharyngitis/tonsillitis: with a recommended dosing regimen of 12 mg/kg on days 1-5, the most common treatment-related side effects were diarrhea (5.4%), abdominal pain (3.4%), vomiting (5.6%), nausea (1.8%), rash (0.7%), and headache (1.1%).

There were no other treatment-related side effects occurring at a frequency of >1% in pediatric practice with any treatment regimen.

The side effects observed with a frequency of ≤1% included the following.

Cardiovascular side: chest pain.

Gastrointestinal disorders: dyspepsia, constipation, anorexia, enteritis, flatulence, gastritis, jaundice, loose stools, oral candidiasis.

With the blood and lymphatic system: anemia, leukopenia.

Nervous system disorders: headache (in case of otitis media), hyperkinesia, dizziness, agitation, nervousness, insomnia.

General: fever, facial swelling, fatigue, fungal infection, malaise, pain.

Allergic: rash and allergic reaction.

Respiratory system: increased cough, pharyngitis, pleural effusion, rhinitis.

Skin and its appendages: eczema, fungal dermatitis, itching, sweating, urticaria, vesiculobulic rash.

Sensory organs: conjunctivitis.

Postmarketing experience

Unwanted reactions reported when taking azithromycin during the postmarketing period in adult and/or pediatric patients for which a causal relationship has not been established include the following.

Allergic reactions: arthralgia, edema, urticaria and angioedema.

Systemic reactions: arrhythmias, including ventricular tachycardia and hypotension. There have been reports of cases of prolonged QT interval and torsade de pointes.

Gastrointestinal disorders: anorexia, constipation, dyspepsia, flatulence, vomiting/diarrhea, rarely leading to dehydration, pseudomembranous colitis, pancreatitis, oral candidiasis, gateway stenosis; there have been rare reports of discolored tongue.

General: asthenia, paresthesia, fatigue, malaise and anaphylaxis (rarely fatal).

Urogenital system disorders: interstitial nephritis, acute renal failure and vaginitis.

Hematopoietic disorders: thrombocytopenia.

Liver/biliary tract disorders: adverse reactions associated with liver dysfunction.

Nervous system disorders: seizures, dizziness/vertigo, headache, drowsiness, hyperactivity, nervousness, agitation and fainting.

Mental disorders: aggressive reactions and anxiety.

Skin and skin appendages: itching, severe skin reactions including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis and DRESS syndrome.

Sensory organs: hearing disorders, including hearing loss, deafness and/or tinnitus, as well as reports of perversion and/or loss of taste/sensation.

Laboratory abnormalities

Adults

Clinically significant abnormalities (without regard to drug association) reported during clinical trials with an incidence greater than 1% have been reported: Decreased Hb, hematocrit, lymphocytes, neutrophils and blood glucose, increased serum CPK, potassium, ALT, GGT, AST, bilirubin, creatinine, blood glucose, platelet count, lymphocytes, neutrophils and eosinophils; with a frequency less than 1%: Leukopenia, neutropenia, decreased sodium, potassium, platelet count, increased monocyte count, basophils, bicarbonate, serum ALP, bilirubin, LDH, and phosphate. Most patients with elevated serum creatinine also had abnormal baseline values.

The changes in laboratory tests were reversible.

In multiple-dose clinical trials involving more than 5,000 patients, 4 patients discontinued azithromycin therapy because of treatment-related liver enzyme abnormalities and 1 because of impaired renal function.

Pediatric patients

One-, three-, and five-day regimens. Laboratory data collected in comparative clinical trials using two 3-day regimens (30 or 60 mg/kg in divided doses for 3 days) or two 5-day regimens (30 or 60 mg/kg) in divided doses for 5 days) were similar in all azithromycin regimens, with the most clinically significant laboratory abnormalities occurring at a rate of 1-5%.

Laboratory data for patients receiving 30 mg/kg as a single dose were collected in a single-center study. In this trial, absolute neutrophil counts between 500-1500 cells/mm3 were observed in 10 of 64 patients receiving 30 mg/kg once, in 9 of 62 patients receiving 30 mg/kg for 3 days, and in 8 of 63 patients in the comparison group. No patient had an absolute neutrophil count < 500 cells/mm3.

In multiple-dose clinical trials involving approximately 4,700 pediatric patients, not one patient had therapy discontinued because of treatment-related laboratory abnormalities.

Overdose

Symptoms: nausea temporary hearing loss vomiting diarrhea.

Treatment: gastric lavage symptomatic therapy.

Pregnancy use

Pregnancy

The FDA fetal category is B.

Teratogenic effects. Reproduction studies have been performed on rats and mice when administered orally at doses to moderately toxic maternal concentrations (i.e., 200 mg/kg/day). These daily doses for rats and mice, depending on body surface area, are estimated to be 4 and 2 times the daily dose of 500 mg for adults, respectively. No evidence of fetal harm due to the effects of azithromycin has been found in animal studies. However, adequate and well-controlled studies in pregnant women have not been conducted. Because animal studies do not always predict effects in humans, azithromycin should only be used during pregnancy if absolutely necessary.

Breastfeeding

It has been reported that azithromycin is excreted in small amounts into human breast milk. Caution should be exercised when azithromycin is used in breastfeeding women.

Similarities