Sumatrolid Solution Tablets (Tablets) Instructions for Use

ATC Code

J01FA10 (Azithromycin)

Active Substance

Azithromycin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antibiotic of the macrolide group – azalide

Pharmacotherapeutic Group

Systemic antibacterial agents; macrolides, lincosamides, and streptogramins; macrolides

Pharmacological Action

Mechanism of action

Azithromycin is a broad-spectrum bacteriostatic antibiotic from the macrolide-azalide group.

The mechanism of action of azithromycin is associated with the suppression of microbial cell protein synthesis.

By binding to the 50S ribosomal subunit, it inhibits peptidyl transferase at the translation stage and suppresses protein synthesis, slowing the growth and reproduction of bacteria.

In high concentrations, it has a bactericidal effect.

Pharmacodynamic effects

It is active against a number of gram-positive, gram-negative, anaerobic, intracellular, and other microorganisms.

Microorganisms may initially be resistant to the antibiotic or may acquire resistance to it.

Scale of microorganism susceptibility to azithromycin (minimum inhibitory concentration (MIC), mg/l

In most cases susceptible microorganisms

1. Gram-positive aerobes

Methicillin-susceptible Staphylococcus aureus

Penicillin-susceptible Streptococcus pneumoniae

Streptococcus pyogenes

2. Gram-negative aerobes

Haemophilus influenzae

Haemophilus parainfluenzae

Legionella pneumophila

Moraxella catarrhalis

Pasteurella multocida

Neisseria gonorrhoeae

3. Anaerobes

Clostridium perfringens

Fusobacterium spp.

Prevotella spp.

Porphyromonas spp.

4. Other microorganisms

Chlamydia trachomatis

Chlamydia pneumoniae

Chlamydia psittaci

Mycoplasma pneumoniae

Mycoplasma hominis

Borrelia burgdorferi

Microorganisms capable of developing resistance to azithromycin

Gram-positive aerobes

Penicillin-resistant Streptococcus pneumoniae

Inherently resistant microorganisms

Gram-positive aerobes

Enterococcus faecalis

Staphylococci (methicillin-resistant staphylococci exhibit a very high degree of resistance to macrolides).

Erythromycin-resistant gram-positive bacteria.

Anaerobes

Bacteroides fragilis

Based on the results of clinical studies conducted in children, the use of azithromycin is not recommended for the treatment of malaria, either as monotherapy or in combination with drugs containing chloroquine or artemisinin, since the fact that azithromycin is not inferior in efficacy to antimalarial drugs recommended for the treatment of uncomplicated malaria has not been established.

Pharmacokinetics

Absorption

After oral administration, azithromycin is well absorbed and rapidly distributed in the body.

After oral administration, the bioavailability is 37%. The C_max in plasma is 0.4 mg/l and is achieved in 2-3 hours.

Distribution

V_d is 31 l/kg. Plasma protein binding is inversely proportional to blood concentration and is 7-50%.

It penetrates cell membranes (effective against infections caused by intracellular pathogens).

It is transported by phagocytes, polymorphonuclear leukocytes, and macrophages to the site of infection, where it is released in the presence of bacteria.

It easily passes through histohematic barriers and enters tissues.

The concentration in tissues and cells is 10-50 times higher than in plasma, and at the site of infection it is 24-34% higher than in healthy tissues.

Metabolism

It is demethylated in the liver, losing activity.

Excretion

Azithromycin has a very long T_1/2 of 35-50 hours. The T_1/2 from tissues is significantly longer.

The therapeutic concentration of azithromycin persists for up to 5-7 days after the last dose.

Azithromycin is excreted mainly unchanged – 50% via the intestines, 6% via the kidneys.

Indications

Infectious and inflammatory diseases caused by microorganisms susceptible to azithromycin:

• Infections of the upper respiratory tract and ENT organs (pharyngitis, tonsillitis, sinusitis, otitis media);
• Infections of the lower respiratory tract (acute bronchitis, exacerbation of chronic bronchitis, pneumonia, including those caused by atypical pathogens);
• Infections of the skin and soft tissues (erysipelas, impetigo, secondarily infected dermatoses, moderate acne vulgaris);
• Initial stage of Lyme disease (borreliosis) – erythema migrans;
• Infections of the genitourinary tract caused by Chlamydia trachomatis (urethritis, cervicitis).

ICD codes

Dosage Regimen

Tablets

Orally.

Take 1 hour before or 2 hours after meals.

Dispersible tablets can be taken in different ways: the tablet can be swallowed whole with water or dissolved in water before administration.

Tablets should be dissolved in at least 50 ml of water.

The resulting suspension should be stirred thoroughly before administration.

Adults

Infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues

500 mg once daily for 3 days (total course dose 1.5 g).

Moderate acne vulgaris

1 tablet (500 mg) once daily for 3 days, then 1 tablet (500 mg) once a week for 9 weeks (total course dose 6.0 g).

The first weekly tablet should be taken 7 days after taking the first daily tablet (day 8 from the start of treatment), the subsequent 8 weekly tablets – at 7-day intervals.

Lyme disease (initial stage of borreliosis) – erythema migrans

Once daily for 5 days: day 1 – 1000 mg, then from day 2 to day 5 – 500 mg daily (total course dose 3.0 g).

Infections of the genitourinary tract caused by Chlamydia trachomatis (urethritis, cervicitis)

Uncomplicated urethritis/cervicitis – 1000 mg as a single dose.

Children

In children aged 12 years and older with body weight over 45 kg, the dosing regimen coincides with the dosing regimen for adult patients.

Children aged 3 to 12 years with body weight less than 45 kg

For infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues: at a dose of 10 mg/kg body weight once daily for 3 days (total course dose 30 mg/kg).

For convenient dosing, it is recommended to use Table 1.

Table No. 1. Calculation of the drug dose for children with body weight less than 45 kg

For pharyngitis/tonsillitis caused by Streptococcus pyogenes: at a dose of 20 mg/kg/day for 3 days (total course dose 60 mg/kg). The maximum daily dose is 500 mg.

Initial stage of Lyme disease: on day 1 – at a dose of 20 mg/kg body weight once daily, then from day 2 to day 5 – daily at a dose of 10 mg/kg body weight once daily (total course dose 60 mg/kg).

Special patient groups

Elderly patients. Dose adjustment is not required.

Since elderly individuals may already have ongoing proarrhythmic conditions, caution should be exercised when using Sumatrolid Solution Tablets due to the high risk of developing arrhythmias, including torsades de pointes.

Patients with impaired renal function. In patients with GFR 10-80 ml/min, dose adjustment is not required.

Patients with GFR < 10 ml/min should take with caution.

Patients with impaired hepatic function. In patients with mild to moderate hepatic impairment, dose adjustment is not required.

Adverse Reactions

The frequency of adverse reactions is presented using the following gradation: very common (≥ 1/10); common (≥ 1/100 but < 1/10); uncommon (≥ 1/1000 but < 1/100); rare (≥ 1/10000 but < 1/1000); very rare (< 1/10000); frequency not known (cannot be estimated from the available data).

Infections and infestations: uncommon – candidiasis, including oral mucosal candidiasis, vaginal infection, pneumonia, fungal infection, bacterial infection, pharyngitis, gastroenteritis, respiratory tract infections, rhinitis; frequency not known – pseudomembranous colitis.

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

Immune system disorders: uncommon – angioedema, hypersensitivity reactions; frequency not known – anaphylactic reaction.

Metabolism and nutrition disorders: uncommon – anorexia.

Nervous system disorders: common – headache; uncommon – dizziness, paresthesia, taste disturbance, somnolence, insomnia, nervousness; rare – agitation; frequency not known – hypoesthesia, anxiety, aggression, syncope, convulsions, psychomotor hyperactivity, loss of smell, loss of taste, parosmia, myasthenia, delirium, hallucinations.

Eye disorders: uncommon – visual impairment.

Ear and labyrinth disorders: uncommon – hearing disorder, vertigo; frequency not known – hearing impairment, including deafness and/or tinnitus.

Cardiac disorders: uncommon – palpitations; frequency not known – QT interval prolongation on ECG, torsades de pointes, ventricular tachycardia.

Vascular disorders: uncommon – flushing; frequency not known – decreased blood pressure.

Respiratory, thoracic and mediastinal disorders: uncommon – dyspnea, epistaxis.

Gastrointestinal disorders: very common – diarrhea; common – nausea, vomiting, abdominal pain; uncommon – flatulence, dyspepsia, constipation, gastritis, dysphagia, abdominal distension, dry mouth, belching, oral mucosal ulcers, increased salivary gland secretion; very rare – tongue discoloration, pancreatitis.

Hepatobiliary disorders: uncommon – hepatitis; rare – impaired liver function, cholestatic jaundice; frequency not known – hepatic failure (in rare cases with a fatal outcome, mainly against the background of severe liver dysfunction), liver necrosis, fulminant hepatitis.

Skin and subcutaneous tissue disorders: uncommon – pruritus, skin rash, urticaria, dermatitis, dry skin, hyperhidrosis; rare – photosensitivity reaction, acute generalized exanthematous pustulosis; frequency not known – Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome).

Musculoskeletal and connective tissue disorders: uncommon – osteoarthritis, myalgia, back pain, neck pain; frequency not known – arthralgia.

Renal and urinary disorders: uncommon – dysuria, renal pain; frequency not known – interstitial nephritis, acute renal failure.

Reproductive system and breast disorders: uncommon – metrorrhagia, testicular dysfunction.

General disorders and administration site conditions: uncommon – edema, asthenia, malaise, feeling of fatigue, facial edema, chest pain, peripheral edema, pyrexia.

Investigations: common – decreased lymphocyte count, increased eosinophil count, increased basophil count, increased monocyte count, increased neutrophil count, decreased plasma bicarbonate concentration; uncommon – increased AST activity, increased ALT activity, increased plasma bilirubin concentration, increased plasma urea concentration, increased plasma creatinine concentration, change in plasma potassium levels, increased plasma alkaline phosphatase activity, increased plasma chloride levels, increased blood glucose concentration, increased platelet count, decreased hematocrit, increased plasma bicarbonate concentration, change in plasma sodium levels.

Contraindications

• Hypersensitivity to azithromycin, erythromycin, other macrolides or ketolides, and/or to any of the excipients of the drug;
• Concomitant use with ergotamine and dihydroergotamine;
• Severe hepatic impairment (Child-Pugh class C);
• Children under 3 years of age;
• Children under 12 years of age with body weight less than 45 kg (for 500 mg tablets).

With caution

Myasthenia gravis; mild to moderate hepatic impairment; end-stage renal failure with GFR (glomerular filtration rate) less than 10 ml/min; in patients with proarrhythmic factors (especially elderly patients): with congenital or acquired QT interval prolongation, 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 imbalance, especially in case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, cardiac arrhythmia or severe heart failure; concomitant use of digoxin, warfarin, cyclosporine.

Use in Pregnancy and Lactation

Pregnancy

Use during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus and child.

Breastfeeding period

Use during breastfeeding only if the expected benefit to the mother outweighs the potential risk to the child.

If it is necessary to use the drug during breastfeeding, it is recommended to discontinue breastfeeding.

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Use in Hepatic Impairment

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

If symptoms of liver dysfunction appear (rapidly increasing asthenia, jaundice, dark urine, tendency to bleed, hepatic encephalopathy), azithromycin therapy should be discontinued and a study of the functional state of the liver should be performed.

Contraindicated: severe hepatic failure (Child-Pugh class B and C).

Use in Renal Impairment

In case of renal impairment: in patients with GFR 10-80 ml/min, no dose adjustment is required; in patients with GFR < 10 ml/min, an increase in the systemic exposure of azithromycin by 33% was observed.

Drug therapy should be conducted with caution under monitoring of renal function.

Contraindicated: severe renal failure (creatinine clearance less than 40 ml/min).

Pediatric Use

Contraindicated in children under 3 years of age.

The drug in the form of tablets containing 500 mg of azithromycin is contraindicated in children under 12 years of age with body weight less than 45 kg.

Geriatric Use

Use with caution in elderly patients due to the risk of proarrhythmic factors.

Special Precautions

As with the use of erythromycin and other macrolides, rare cases of serious allergic reactions, including angioedema and anaphylaxis (in rare cases with fatal outcome), skin reactions, including acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis (in rare cases with fatal outcome), drug rash with eosinophilia and systemic symptoms (DRESS syndrome) have been reported.

Some of these reactions that developed while taking azithromycin had a recurrent course and required prolonged treatment and observation.

If an allergic reaction occurs, the drug should be discontinued and appropriate treatment initiated.

It should be borne in mind that after discontinuation of symptomatic therapy, symptoms of an allergic reaction may recur.

In case of missing a single dose of the drug, the missed dose should be taken as soon as possible, and subsequent doses should be taken at 24-hour intervals.

Sumatrolid Solution Tablets should be taken at least 1 hour before or 2 hours after taking antacid drugs.

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

If symptoms of liver dysfunction appear, such as rapidly increasing asthenia, jaundice, dark urine, tendency to bleed, hepatic encephalopathy, therapy with Sumatrolid Solution Tablets should be discontinued and a study of the functional state of the liver should be performed.

In cases of renal impairment: no dose adjustment is required in patients with a GFR of 10-80 ml/min; in patients with a GFR < 10 ml/min, a 33% increase in the systemic exposure to azithromycin was observed. Therapy with Sumatrolid Solution Tablets should be conducted with caution under monitoring of renal function.

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

Sumatrolid Solution Tablets should not be taken for longer courses than indicated in the instructions, because the pharmacokinetic properties of azithromycin allow for a short and convenient dosing regimen.

There are no data on the possible interaction between azithromycin and ergotamine and dihydroergotamine derivatives, but due to the development of ergotism with the concomitant use of macrolides with ergotamine and dihydroergotamine derivatives, this combination is contraindicated.

With prolonged use of Sumatrolid Solution Tablets, the development of Clostridium difficile-associated pseudomembranous colitis is possible, ranging from mild diarrhea to severe colitis. In case of antibiotic-associated diarrhea during the administration of Sumatrolid Solution Tablets, as well as within 2 months after the end of therapy, clostridial pseudomembranous colitis should be ruled out. Drugs that inhibit intestinal peristalsis are contraindicated.

During treatment with macrolides, including azithromycin, slowing of cardiac repolarization and QT interval prolongation have been observed, which increase the risk of cardiac arrhythmias, including torsades de pointes.

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

Before prescribing Sumatrolid Solution Tablets to all patients taking hydroxychloroquine or chloroquine, carefully weigh the benefit-risk ratio due to a potentially increased risk of cardiovascular events and cardiovascular mortality (see the “Drug Interactions” section).

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

Effect on the ability to drive vehicles and operate machinery

If adverse effects on the nervous system and organ of vision occur, caution should be exercised when performing activities requiring increased concentration and speed of psychomotor reactions.

Overdose

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

Treatment: symptomatic.

Drug Interactions

Antacids

Antacids do not affect the bioavailability of azithromycin but reduce C_max in the blood by 30%, therefore Azithromycin should be taken at least 1 hour before or 2 hours after taking these drugs and food.

Cetirizine

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

Didanosine (dideoxyinosine)

Concomitant 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 antibacterial drugs, including azithromycin, with P-glycoprotein substrates, such as digoxin and colchicine, leads to an increase in the serum concentration of the P-glycoprotein substrate. Thus, when digoxin and azithromycin are taken concomitantly, the possibility of an increase in the serum concentration of digoxin should be considered.

Zidovudine

Concomitant use of azithromycin (single dose of 1000 mg and multiple doses of 1200 mg or 600 mg) has a slight 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 the cytochrome P450 system isoenzymes. Azithromycin has not been shown to be involved 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, concomitant use of azithromycin with ergot alkaloid derivatives is contraindicated.

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

Atorvastatin

Concomitant administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause changes in plasma atorvastatin concentrations (based on HMG-CoA reductase inhibition analysis). However, isolated cases of rhabdomyolysis have been reported post-marketing in patients receiving Azithromycin and statins concomitantly.

Carbamazepine

Pharmacokinetic studies in healthy volunteers did not reveal a significant effect on the plasma concentration of carbamazepine and its active metabolite in patients receiving Azithromycin concomitantly.

Cimetidine

Pharmacokinetic studies did not reveal an effect of a single dose of cimetidine on the pharmacokinetics of azithromycin, provided cimetidine was administered 2 hours before azithromycin.

Indirect-acting anticoagulants (coumarin derivatives)

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

Cyclosporine

In pharmacokinetic studies involving healthy volunteers who took Azithromycin orally (500 mg/day as a single dose) for 3 days and then cyclosporine (10 mg/kg/day as a single dose), a significant increase in C_max in plasma and AUC_0-5 of cyclosporine was revealed. Caution should be exercised with the concomitant use of these drugs. If concomitant use of these drugs is necessary, monitoring of cyclosporine plasma concentration and appropriate dose adjustment should be performed.

Efavirenz

Concomitant administration of azithromycin (600 mg/day as a single dose) and efavirenz (400 mg/day) daily for 7 days did not cause any clinically significant pharmacokinetic interaction.

Fluconazole

Concomitant use of azithromycin (1200 mg as a single dose) did not alter the pharmacokinetics of fluconazole (800 mg as a single dose). Total exposure and T_1/2 did not change with concomitant fluconazole administration; however, an 18% decrease in C_max of azithromycin was noted, which was not clinically significant.

Indinavir

Concomitant use of azithromycin (1200 mg as a single dose) did not cause a statistically significant effect on the pharmacokinetics of indinavir (800 mg 3 times/day for 5 days).

Methylprednisolone

Azithromycin does not significantly affect the pharmacokinetics of methylprednisolone.

Nelfinavir

Concomitant use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times/day) causes an increase in the steady-state plasma concentrations of azithromycin. No clinically significant adverse effects were observed and no adjustment of the azithromycin dose is required when taken concomitantly with nelfinavir.

Rifabutin

Concomitant use of azithromycin and rifabutin does not affect the plasma concentration of each drug. Neutropenia was sometimes observed with the concomitant use of azithromycin and rifabutin. Although neutropenia was 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

Studies in healthy volunteers did not provide data confirming an effect of azithromycin (500 mg/day daily for 3 days) on the C_max in plasma and AUC of sildenafil or its main circulating metabolite.

Terfenadine

Pharmacokinetic studies have not provided data confirming an interaction between azithromycin and terfenadine. Isolated cases have been reported where the possibility of such an interaction could not be completely excluded, but there was no specific evidence that such an interaction occurred. It has been established that concomitant use of terfenadine and macrolide antibiotics can cause arrhythmia and QT interval prolongation.

Theophylline

No interaction between azithromycin and theophylline has been identified.

Triazolam/Midazolam

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

Trimethoprim/Sulfamethoxazole

Concomitant use of trimethoprim/sulfamethoxazole with azithromycin did not reveal a significant effect on C_max, total exposure, or renal excretion of trimethoprim or sulfamethoxazole. The plasma concentration of azithromycin corresponded to that found in other studies.

Hydroxychloroquine and Chloroquine

Observational data have shown that concomitant use of azithromycin with hydroxychloroquine in patients with rheumatoid arthritis is associated with an increased risk of cardiovascular events and cardiovascular mortality. Due to a possible similar risk with the use of other macrolides in combination with hydroxychloroquine or chloroquine, the benefit-risk ratio should be carefully weighed before prescribing Sumatrolid Solution Tablets to any patients taking hydroxychloroquine or chloroquine.

Storage Conditions

The drug should be stored out of the reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.