Sumamed (Azitromicin)

In 1 gram of powder:

azithromycin dihydrate - 25.047 mg, which corresponds to the content of azithromycin - 23.895 mg

Excipients :

sucrose - 929.753 mg,

sodium phosphate - 20 mg,

hyprolose - 1.6 mg,

xanthan gum - 1.6 mg,

strawberry flavoring - 10 mg,

titanium dioxide - 5 mg,

silicon dioxide colloidal - 7 mg.

Pharmacological action  - broad-spectrum antibacterial.

Azithromycin is a broad-spectrum bacteriostatic antibiotic from the group of azrolide macrolides. It has a wide range of antimicrobial effects. The mechanism of action of azithromycin is associated with the suppression of protein synthesis of microbial cells. By binding to the 50S subunit of the ribosome, it inhibits the peptide translocase at the translation stage and inhibits protein synthesis, slowing the growth and reproduction of bacteria. In high concentrations it has a bactericidal effect.

It has activity against a number of gram-positive, gram-negative, anaerobic, intracellular and other microorganisms. Microorganisms may initially be resistant to the action of an antibiotic or may become resistant to it.

In most cases, sensitive microorganisms:  gram-positive aerobes -  Staphylococcus aureus (methicillin-sensitive strains), Streptococcus pneumoniae  (penicillin- sensitive  strains),  Streptococcus pyogenes ; gram-negative aerobes -  Haemophilus influenzae ,  Haemophilus parainfluenzae ,  Legionella pneumophila , Moraxella catarrhalis ,  Pasteurella multocida ,  Neisseria gonorrhoeae ; anaerobes -  Clostridium perfringens ,  Fusobacterium spp. , Prevotella spp. ,  Porphyromonas spp.; other microorganisms -  Chlamydia trachomatis ,  Chlamydia pneumoniae ,  Chlamydia psittaci ,  Mycoplasma pneumoniae ,  Mycoplasma hominis ,  Borrelia burgdorferi .

Microorganisms that can develop resistance to azithromycin : gram-positive aerobes -  Streptococcus pneumoniae  (penicillin-resistant strains).

Initially resistant microorganisms : gram-positive aerobes -  Enterococcus faecalis ,  Staphylococci (methicillin-resistant strains with a very high frequency have acquired resistance to macrolides), gram-positive bacteria, resistant to erythromycin; anaerobic microorganisms.

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug:

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

- lower respiratory tract infections (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, acne vulgaris of moderate severity (for tablets));

- The initial stage of Lyme disease (borreliosis) - erythema migrans (erythema migrans);

- urinary tract infections (urethritis, cervicitis) caused by Chlamydia trachomatis (for tablets and capsules).

During pregnancy and during breastfeeding, the use of the drug is possible only if the expected potential benefit of therapy for the mother outweighs the potential risk to the fetus and baby.

If it is necessary to use the drug during lactation, breastfeeding should be suspended.

WHO recommends azithromycin as the drug of choice for treating chlamydial infections in pregnant women.

- severe liver dysfunction;

- severe renal impairment (CC <40 ml / min);

- simultaneous administration with ergotamine and dihydroergotamine;

- children under 12 years old with body weight <45 kg (for capsules and tablets 500 mg);

- children's age up to 3 years (for tablets 125 mg);

- children's age up to 6 months (for powder for suspension);

- deficiency of sucrose / isomaltase, fructose intolerance, glucose-galactose malabsorption (for powder for suspension);

- Hypersensitivity to azithromycin, erythromycin, other macrolides or ketolides, or other components of the drug.

Carefully:

Myasthenia gravis; impaired liver function of mild to moderate severity; impaired renal function of mild to moderate severity (CC> 40 ml / min); in patients with proarrhythmogenic factors (especially in old age) - with congenital or acquired prolongation of the QT interval, in patients receiving antiarrhythmic drugs of classes IA (quinidine, procainamide) and III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with impaired water-electrolyte balance, especially with hypokalemia or hypomagnesemia, with clinically significant bradycardia, arrhythmia, or severe heart failure; with the simultaneous use of digoxin, warfarin, cyclosporine;

The frequency of side effects is classified according to WHO recommendations: very often (≥10%), often (≥1% - <10%), infrequently (≥0.1% - <1%), rarely (≥0.01% - <0.1%) , very rarely (<0.01%), unknown frequency (impossible to estimate based on available data).

Infectious diseases:  infrequently - candidiasis (including the mucous membrane of the oral cavity and genitals), pneumonia, pharyngitis, gastroenteritis, respiratory diseases, rhinitis; unknown frequency - pseudomembranous colitis.

On the part of the blood and lymphatic system:  infrequently - leukopenia, neutropenia, eosinophilia; very rarely - thrombocytopenia, hemolytic anemia.

From the side of metabolism:  infrequently - anorexia.

Allergic reactions:  infrequently - angioedema, hypersensitivity reaction; unknown frequency - anaphylactic reaction.

From the nervous system:  often - headache; infrequently - dizziness, violation of taste, paresthesia, drowsiness, insomnia, nervousness; rarely - agitation; unknown frequency - hypesthesia, anxiety, aggression, fainting, convulsions, psychomotor hyperactivity, loss of smell, perversion of smell, loss of taste, myasthenia gravis, delirium, hallucinations.

From the side of the organ of vision:  infrequently - impaired vision.

On the part of the hearing organ and labyrinth disorders:  infrequently - hearing impairment, vertigo; unknown frequency - hearing impairment up to deafness and / or tinnitus.

From the cardiovascular system:  infrequently - a feeling of palpitations, flushing of the face; unknown frequency - decreased blood pressure, increased QT interval on the ECG, pirouette type arrhythmia, ventricular tachycardia.

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

From the digestive system:  very often - diarrhea; often - nausea, vomiting, abdominal pain; infrequently - flatulence, dyspepsia, constipation, gastritis, dysphagia, bloating, dryness of the oral mucosa, belching, ulcers of the oral mucosa, increased secretion of the salivary glands; very rarely - discoloration of the tongue, pancreatitis.

On the part of the liver and biliary tract:  infrequently - hepatitis; rarely - impaired liver function, cholestatic jaundice; unknown frequency - liver failure (in rare cases with a fatal outcome mainly due to severe impairment of liver function), liver necrosis, fulminant hepatitis.

On the part of the skin and subcutaneous tissues:  infrequently - skin rash, dermatitis, dry skin, sweating; rarely - photosensitivity reaction; unknown frequency - Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.

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

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

From the genitals and mammary gland:  infrequently - metrorrhagia, impaired testicular function.

Other:  infrequently - asthenia, malaise, feeling tired, face swelling, chest pain, fever, peripheral edema.

Laboratory 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 blood plasma; infrequently - an increase in the activity of AST, ALT, an increase in the concentration of bilirubin in the
blood plasma , an increase in the concentration of urea in the blood plasma, an increase in the concentration of creatinine in the blood plasma, a change in the potassium content in the blood plasma, an increase in the activity of alkaline phosphatase in the blood plasma, an increase in the chlorine content in the blood plasma , an increase in the concentration of glucose in the blood, an increase in the number of platelets, an increase in hematocrit, an increase in the concentration of bicarbonates in the blood plasma, a change in the sodium content in the blood plasma.

Antacids

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

Cetirizine

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

Digoxin (P-glycoprotein substrates)

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

Zidovudine

The simultaneous use of azithromycin (a single dose of 1000 mg and a multiple dose of 1200 mg or 600 mg) has a slight effect on the pharmacokinetics, including excretion by the kidneys 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 weakly interacts with isoenzymes of the cytochrome P450 system. It was not found that azithromycin is involved in a pharmacokinetic interaction similar to erythromycin and other macrolides. Azithromycin is not an inhibitor and inducer of isoenzymes of the cytochrome P450 system.

Ergot alkaloids

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

Pharmacokinetic studies of the simultaneous use of azithromycin and drugs, the metabolism of which occurs with the participation of isoenzymes of the cytochrome P450 system, have been conducted.

Atorvastatin

The simultaneous use of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause a change in plasma concentrations of atorvastatin (based on the analysis of inhibition of GMK-CoA reductase). However, in the post-registration period, individual reports of cases of rhabdomyolysis in patients receiving both azithromycin and statins were received.

Carbamazepine

In pharmacokinetic studies involving healthy volunteers, there was no significant effect on the concentration of carbamazepine and its active metabolite in blood plasma in patients treated with azithromycin simultaneously.

Cimetidine

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

Indirect anticoagulants (coumarin derivatives)

In pharmacokinetic studies, azithromycin did not affect the anticoagulant effect of warfarin when taken in a single dose of 15 mg by healthy volunteers. Potentiation of the anticoagulant effect has been reported after the simultaneous use of azithromycin and indirect anticoagulants (coumarin derivatives). Despite the fact that a causal relationship has not been established, it is necessary to take into account the need for frequent monitoring of prothrombin time with the use of azithromycin in patients who receive oral anticoagulants of indirect action (coumarin derivatives).

Cyclosporin

In a pharmacokinetic study involving healthy volunteers who took azithromycin (500 mg / day once) and then cyclosporine (10 mg / kg / day once) for 3 days, a significant increase in plasma Cmax and AUC0-5 cyclosporine were detected . With this combination, caution is required. If necessary, the simultaneous use of these drugs should monitor the concentration of cyclosporine in blood plasma and adjust the dose accordingly.

Efavirenz

The simultaneous use of azithromycin (600 mg / day once) and efavirenza (400 mg / day) daily for 7 days did not cause any clinically significant pharmacokinetic interaction.

Fluconazole

The simultaneous use of azithromycin (1200 mg once) did not change the pharmacokinetics of fluconazole (800 mg once). The total exposure and T1 / 2azithromycin did not change with the simultaneous use of fluconazole, however, a decrease in Cmax of azithromycin (by 18%) was observed, which had no clinical significance.

Indinavir

The simultaneous use of azithromycin (1200 mg once) 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

The simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times / day) causes an increase in Css of azithromycin in blood plasma. No clinically significant side effects were observed and dose adjustment of azithromycin with its simultaneous use with nelfinavir is not required.

Rifabutin

The simultaneous use of azithromycin and rifabutin does not affect the concentration of each drug in the blood plasma. With the simultaneous use of azithromycin and rifabutin, neutropenia was sometimes observed. Although neutropenia has been associated with rifabutin, a causal relationship between 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 AUC and Cmax of sildenafil or its main circulating metabolite.

Terfenadine

In pharmacokinetic studies, evidence of an interaction between azithromycin and terfenadine has not been obtained. Isolated cases were reported when the possibility of such an interaction could not be completely ruled out, but there was no concrete evidence that such an interaction took place. It was found that the simultaneous use of terfenadine and macrolides can cause arrhythmia and lengthening of the QT interval.

Theophylline

No interaction was found between azithromycin and theophylline.

Triazolam / Midazolam

Significant changes in pharmacokinetic parameters with the simultaneous use of azithromycin with triazolam or midazolam in therapeutic doses were not detected.

Trimethoprim / sulfamethoxazole

With the simultaneous use of trimethoprim / sulfamethoxazole with azithromycin, there was no significant effect on Cmax, the total exposure or excretion by the kidneys of trimethoprim or sulfamethoxazole. Serum azithromycin concentrations were consistent with those found in other studies.

Inside , 1 time per day, 1 hour before or 2 hours after a meal. After taking Sumamed®, the child must be invited to drink a few sips of water so that he can swallow the rest of the suspension.

Before each dose, the contents of the vial are thoroughly shaken until a homogeneous suspension is obtained. If the required volume of the suspension has not been taken from the vial within 20 minutes after shaking, the suspension should be shaken again, the required volume should be taken and given to the child.

The required dose is measured using a dosing syringe with a division price of 1 ml and a nominal suspension capacity of 5 ml (100 mg of azithromycin) or a measuring spoon with a nominal suspension capacity of 2.5 ml (50 mg of azithromycin) or 5 ml (100 mg of azithromycin) in cardboard packaging with a bottle.

After use, the syringe (having previously disassembled it) and a measuring spoon are washed with running water, dried and stored in a dry place until the next dose of Sumamed®.

Infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues: the  drug is prescribed at the rate of 10 mg / kg 1 time per day for 3 days; course dose - 30 mg / kg.

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

Treatment:  symptomatic therapy.

If you miss one dose of the drug, the missed dose should be taken as soon as possible, and the next ones should be taken at intervals of 24 hours.

Sumamed® should be taken at least 1 hour before or 2 hours after taking antacid drugs.

Sumamed® should be used with caution in patients with impaired liver function of mild to moderate severity due to the possibility of developing fulminant hepatitis and severe liver failure. In the presence of symptoms of impaired liver function, such as rapidly increasing asthenia, jaundice, dark urine, a tendency to bleeding, hepatic encephalopathy, Sumamed® therapy should be discontinued and a study of the functional state of the liver should be carried out.

In case of impaired renal function of mild to moderate severity (CC> 40 ml / min), Sumamed® therapy should be carried out with caution under the control of the state of renal function.

As with the use of other antibacterial drugs, during therapy with Sumamed®, patients should be regularly examined for the presence of unresponsive microorganisms and signs of superinfection, including fungal.

Sumamed® should not be used in longer courses than indicated in the instructions, as The pharmacokinetic properties of azithromycin make it possible to recommend a short and simple dosage regimen.

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

With prolonged use of Sumamed®, pseudomembranous colitis caused by Clostridium difficile may develop, both in the form of mild diarrhea and severe colitis. With the development of antibiotic-associated diarrhea while taking Sumamed®, and also 2 months after the end of therapy, pseudomembranous colitis should be excluded.

In the treatment of macrolides, including azithromycin, there was an increase in cardiac repolarization and QT interval, increasing the risk of developing cardiac arrhythmias, including pirouette arrhythmias.

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

The use of the drug Sumamed® can provoke the development of myasthenic syndrome or cause an exacerbation of myasthenia gravis.

When used in patients with diabetes mellitus, as well as in patients on a low-calorie diet, it must be borne in mind that sucrose (0.32 XU / 5 ml) is included in the composition of the powder for the preparation of Sumamed® suspension.

Influence on the ability to drive vehicles and control mechanisms

With the development of undesirable effects from the nervous system and organ of vision, caution should be exercised when performing actions requiring an increased concentration of attention and speed of psychomotor reactions.