Tremac-Sanovel - instructions for use, dose, side effects, contraindications

active substance: azithromycin dihydrate (equivalent to azithromycin) 209.64 mg (200 mg) Excipients: sucrose 4447.443 mg, sodium phosphate 20.1 mg, giprolose 7.65 mg, xanthan gum 7.65 mg, cherry flavor 55.483 mg, banana flavor 28.7 mg.

Description:White homogeneous powder with the smell of cherry and banana. After dissolving in a solvent - a homogeneous suspension of white or light yellow color with the smell of cherry and banana. Solvent (water purified) - a clear, colorless liquid.

Pharmacotherapeutic group:Antibiotic - azalide

ATX: & nbsp

J.01.F.A.10 Azithromycin

Pharmacodynamics:

Antibacterial agent of a wide spectrum of action, azalide, acts bacteriostatically. The mechanism of action is due to the suppression of protein synthesis of a sensitive microorganism by binding to 50S subunit of ribosomes, inhibits peptidyltranslokase at the stage of translation. Slows the growth and multiplication of bacteria, in high concentrations has a bactericidal effect. It has activity against a number of gram-positive, gram-negative, anaerobes, intracellular and other microorganisms.

Minimal inhibitory concentration (MIC90) < 0.01 μg / ml

Mycoplasma pneumoniae	Haemophilus ducreyi
	MIC90 = 0.01-0.1 mcg / ml
Moraxella catarrhalis	Propionibacterium acnes
Gardnerella vaginalis	Actinomyces species
Bordetella pertussis	Borrelia burgdorferi
Mobiluncus species	MIC90 = 0.1 -2.0 mcg / ml
Haemophilus influenzae	Streptococcus pyogenes
Haemophilus parainfluenzae	Streptococcus pneumoniae
Legionella pneumophila	Streptococcus agalactiae
Neisseria meningitidis	Streptococcus viridans
Neisseria gonorrhoeae	Streptococcus groups C, F and G
Helicobacter pylori	Peptococcus species
Campylobacter jejuni	Peptostreptococcus
Pasteurella multocida	Fisobacterium necrophorum
Pasteurella melitensis	Clostridium perfringens
Bordetella parapertussis	Bacteroides bivius
Vibrio cholerae	Chlamydia trachomatis
Plesiomonas shigelloides	Chlamydia pneumoniae
Staphylococcus aureus	Ureaplasma urealyticum
Staphylococcus epidermidis	Listeria monocitogenes
	MIC90 = 2.0-8.0 mcg / ml
Escherichia coli	Bacteroides fragilis
Salmonella enteritidis	Bacteroides oralis
Salmonella typhi	Clostridium difficile
Shigella sonnei	Eubacterium lentum
Yersinia enterocolitica	Fusobacterium nucleatum
Acinetobacter calcoaceticus	Aeromonas hydrophilia

Pharmacokinetics:

Absorption is high, acid-fast, lipophilic. Quickly absorbed in the gastrointestinal tract. Bioavailability after a single dose of 500 mg is 37% (the effect of "first passage" through the liver).The maximum concentration (Cmah) after intake of 500 mg is 0.4 mg / l, the time to reach the maximum concentration (TCma) of the drug in plasma is 2.5-2.9 hours; in tissues and cells the concentration is 10-50 times higher than in serum, the volume of distribution is 31.1 l / kg. Easily passes the histohematological barriers. It penetrates well into the respiratory tract, organs and tissues of the genitourinary system, into the skin and soft tissues; accumulates in a medium with low pH, in lysosomes (which is especially important for the eradication of intracellularly located pathogens). It is also transported by phagocytes, polymorphonuclear leukocytes and macrophages. It penetrates the membranes of cells and creates high concentrations in them. It remains in effective concentrations for 5-7 days after the last dose. The connection with plasma proteins is 7-50% (inversely proportional to the concentration in the blood). In the liver demethylated, the metabolites formed are inactive. In the metabolism of azithromycin, isozymes participate CYP3A4, CYP3A5, CYP3A7,; of which it is an inhibitor. Plasma clearance - 630 ml / min; half-life (T1 / 2) between 8 and 24 hours after admission - 14-20 hours, T1 / 2 in the interval from 24 to 72 hours - 41 hours 50 %'. It is excreted with bile in unchanged form, 6% - with kidneys.

Eating significantly changes the pharmacokinetics: C_m_Oh increases by 46%, the area under the pharmacokinetic curve (AUC) increases by 14%.

In elderly men (65-85 years), the pharmacokinetic parameters do not change, in women C increases_m_Oh by 30-50%.

Indications:

Infectious-inflammatory diseases caused by microorganisms susceptible to azithromycin:

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

- infections of the lower respiratory tract (pneumonia, including atypical bronchitis, including acute, exacerbation of chronic);

- infections of the skin and soft tissues (erysipelas, impetigo, secondarily infected dermatoses);

- Lyme disease (the initial stage is chronic migrating erythema "erythema migrans").

Contraindications:

- Hypersensitivity to azithromycin (including antibiotics of the macrolide group), components of the drug;

- Severe hepatic insufficiency (class C on the Child-Pugh scale);

- Severe renal insufficiency (creatinine clearance less than 40 ml / min);

- Children under 3 years;

- Deficiency of sucrose / isomaltase, intolerance to fructose, glucose-galactose malabsorption;

- Simultaneous reception with ergotamine and dihydroergotamine.

Carefully:

Arrhythmia (risk of ventricular arrhythmia and lengthening of the interval Q - T), hepatic insufficiency of mild and moderate severity (classes A and B on the Child-Pugh scale) and / or renal failure (creatinine clearance more than 40 ml / min), co-administration with terfenadine, warfarin, digoxin, myasthenia gravis.

Pregnancy and lactation:

Azithromycin in pregnancy is prescribed only if the expected benefit for the mother exceeds the potential risk to the fetus.

If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside, 1 time per day, at least 1 hour before or 2 hours after meals.

In infections of the upper and lower respiratory tract. skin and soft tissues (except for erythema migrans) a total dose of 30 mg / kg, i.e. 10 mg / kg body weight once a day for 3 days.

Children are dosed based on weight:

Body weight, kg	The volume of the drug, in ml (the amount of azithromycin in mg)
10-14	2.5 ml (100 mg) - V2 measuring spoon
15-24	5 ml (200 mg) -1 measuring spoon
25-34	7.5 ml (300 mg) - ½ measuring spoon
35-44	10 ml (400 mg) - 2 measuring spoons
>45	12.5 ml (500 mg) - 2 ½ measuring spoons

With Lyme disease (for the treatment of stage I - erythema migrans) the total dose of the drug is 60 mg / kg: once a day to 20 mg / kg - on the 1st day and 10 mg / kg - on subsequent days from 2 to 5 days.

In the event that the dose was missed, it should be taken as soon as possible, and then the subsequent doses should be taken at intervals of 24 hours.

In patients with moderate impairment of renal function (creatinine clearance> 40 ml / min), dose adjustment is not needed.

Preparation of the suspension: Water from a plastic vial is added to the vial of powder. Before taking the contents of the vial, shake until a homogeneous suspension is obtained. To dispense the finished suspension, use a syringe or a measuring spoon. Immediately after taking the suspension, the child is given a few sips of tea or juice to wash and swallow the remaining amount of the suspension in the mouth. After use, the syringe is disassembled and washed with running water, dried and stored together with the preparation.

Side effects:

From the digestive system: nausea, vomiting, diarrhea, indigestion, anorexia, constipation, gastritis, candidamycosis of the oral mucosa, discoloration of the tongue, pancreatitis, pseudomembranous colitis, impaired liver function, hyperbilirubinemia, hepatitis, hepatic insufficiency (possibly fatal, mainly on the background of a violation of liver function), liver necrosis,fulminant hepatitis, cholestatic jaundice, abdominal pain / spasms, flatulence, digestive disorders, changes in laboratory parameters of liver function, decreased appetite; In addition, children - constipation, decreased appetite, gastritis, candidamycosis of the oral mucosa.

From the cardiovascular system: palpitation, lowering blood pressure, increasing the interval QT, arrhythmia of the "pirouette" type, bidirectional ventricular tachycardia; children have chest pain.

From the nervous system: paresthesia, taste disorders, hypoesthesia, insomnia, drowsiness, asthenia, anxiety, aggression, fainting, convulsions, psychomotor hyperactivity, loss of smell, taste sensations, myasthenia gravis, headache; children - headache (with medication otitis media), hyperkinesia, anxiety, neurosis, sleep disturbances.

From the sense organs: violation of the clarity of visual perception, deafness, tinnitus, vertigo, a violation of the perception of taste and smell.

From the hematopoiesis: lymphopenia, eosinophilia, hemolytic anemia, thrombocytopenia.

From the genitourinary system: vaginal candidiasis, hypercreatininaemia, interstitial nephritis, acute renal failure.

Allergic reactions: hypersensitivity reaction, photosensitivity, Anaphylactic reaction, including Quincke's edema (in rare cases with fatal outcome), itching, skin rashes, angioedema, hives, eosinophilia, erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome.

From the musculoskeletal system: arthralgia.

Other: weakness, candidiasis, chest pain, peripheral edema, asthenia, malaise, photosensitivity; children have conjunctivitis, a change in taste.

Overdose:

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

Treatment: symptomatic therapy.

Interaction:

Antacids (aluminum and magnesium-containing) do not affect bioavailability, but reduce the concentration of azithromycin in the blood by 30%, so the interval between their intake should be 1 hour before or 2 hours after taking these dosage forms.

When used simultaneously with derivatives of ergotamine and dihydroergotamine, the toxic effect (vasospasm, dysesthesia) of the latter is likely to increase.

When used simultaneously with anticoagulants, the indirect action of the coumarin series (warfarin) and azithromycin (in usual doses) patients need careful monitoring of prothrombin time.

Caution should be exercised in the joint appointment of terfenadine and azithromycin, since it was found that the simultaneous administration of terfenadine and macrolides causes arrhythmia and lengthening Q - T interval. Proceeding from this, it is impossible to exclude the aforementioned complications in the joint administration of terfenadine and azithromycin.

With simultaneous use with digoxin, it is necessary to control the concentration of digoxin in the blood (there may be an increase in absorption of digoxin in the intestine). - With simultaneous application with cyclosporine, it is necessary to monitor the concentration of cyclosporin in the blood.

With simultaneous use with nelfinavir, the incidence of side effects of azithromycin may increase (hearing loss, increased activity of "liver" transaminases).

When combined with zidovudine azithromycin does not affect the pharmacokinetic parameters of zidovudine in the blood plasma or on the excretion by the kidneys of its and its metabolite glucuronide,but the concentration of the active metabolite of phosphorylated zidovudine in mononuclear cells of peripheral vessels increases. The clinical significance of this fact is not determined.

The possibility of inhibiting the isoenzyme should be considered CYP3A4 with the simultaneous use of azithromycin with cyclosporine, terfenadine, ergot alkaloids, cisapride, pimozide, quinidine, astemizole and other drugs the metabolism of which occurs with the participation of this enzyme.

Azithromycin does not affect the concentration of carbamazepine, cimetidine, didanosine, efavirenz, fluconazole, indinavir, midazolam, theophylline, triazolam, trimethoprim / sulfamethoxazole, cetirizine, sildenafil, atorvastatin, rifabutin and methylprednisolone in the blood together.

Special instructions:

In case of missed dose, the missed dose should be taken as soon as possible, and the subsequent dose should be taken at intervals of 24 hours.

Azithromycin should be taken 1 hour before or 2 hours after taking antacid medicines.

Take with caution patients with moderate hepatic impairment because of the possibility of developing fulminant hepatitis and severe hepatic insufficiency in such patients.

In the presence of symptoms of liver dysfunction (rapidly increasing asthenia, jaundice, darkening of the urine, a tendency to bleeding, hepatic encephalopathy) therapy with azithromycin should be discontinued and an examination of the functional state of the liver should be carried out.

With moderate renal failure (creatinine clearance more than 40 ml / min), azithromycin should be administered under the control of kidney function.

Contraindicated simultaneous administration of azithromycin with derivatives of ergotamine and dihydroergotamine because of the possible development of ergotism.

When using the drug, both on the background of taking and 2-3 weeks after discontinuation of treatment, it is possible to develop diarrhea caused by Clostridium difficile (pseudomembranous colitis). In mild cases, it is sufficient to cancel the treatment and apply ion-exchange resins (colestramine, colestipol), in severe cases, compensation for loss of fluid, electrolytes and protein, the appointment of vancomycin, bacitracin or metronidazole.

Do not use drugs that inhibit the intestinal motility. Since it is possible to extend the interval Q-Ty patients receiving macrolides, including azithromycin, when using azithromycin, caution should be exercised in patients with known risk factors for lengthening the interval Q - T: old age; violation of electrolyte balance (hypokalemia, hypomagnesemia); syndrome

congenital lengthening interval Q - T; heart disease (heart failure, myocardial infarction, bradycardia); simultaneous reception of drugs that can lengthen the interval Q - T (including antiarrhythmic drugs IA and III classes, tricyclic and tetracyclic antidepressants, neuroleptics, fluoroquinolones).

With the use of azithromycin, the development of myasthenic syndrome or myasthenia exacerbation is possible.

Indication for patients with diabetes mellitus

The digestible carbohydrates contained in 5 ml of the suspension are about 0.4 "bread unit" (XE).

Effect on the ability to drive transp. cf. and fur:During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:Powder for the preparation of a suspension for oral administration (for children) 200 mg / 5 ml.

Packaging:

Powder for preparation of suspension for oral administration (for children) 200 mg / 5 ml:

14.330 g (corresponding to 0.6 g azithromycin) or 28.660 g (corresponding to 1.2 g azithromycin) powder to produce 15 ml or 30 ml of suspension are placed in a plastic vial containing a cover containing silica gel and a protective ring.

Solvent (purified water)

Polyethylene containers of 7.5 ml, 15 ml of purified water.

1 bottle together with the solvent, instructions for use, a measuring spoon for 5 ml and a syringe for dosing are put in a cardboard box.

Storage conditions:

Powder for preparation of suspension for oral administration (for children) 200 mg / 5 ml:

In dry, the dark place at a temperature of no higher than 30 ° C.

Solvent (purified water):

In a dry place at a temperature of no higher than 25 ° C.

The prepared suspension is at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

2 years. The solvent (purified water) is 5 years.

The prepared suspension is 5 days.

Do not use after the time specified on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000865

Date of registration:14.10.2011

The owner of the registration certificate:Sanovel Pharmaco-industrial trading companySanovel Pharmaco-industrial trading company Turkey

Manufacturer: & nbsp

SANOVEL PHARMACEUTICAL PRODUCTS IND., Inc. Turkey

Representation: & nbspSANOVEL branch of the company pharmaco-industrial trading companySANOVEL branch of the company pharmaco-industrial trading companyRussia

Information update date: & nbsp31.08.2015

Illustrated instructions

Instructions

Tremac-Sanovel (Tremak-Sanovel)