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

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. Effects on extracorporeal and intracellular pathogens.

The activity of azithromycin against most strains of the following microorganisms is proved as in vitro, and in clinical practice:

Aerobic Gram-positive microorganisms: Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes;

Azithromycin exhibits cross-resistance to erythromycin-resistant gram-positive strains. Most strains Enterococcus faecalis and methicillin-resistant staphylococci are resistant to azithromycin.

Aerobic gramotropic microorganisms: Haemophilus ducreyi, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae;

Other: Chlamydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae. Beta-lactamases do not affect the activity of azithromycin.

The activity of azithromycin in vitro:

Aerobic Gram-positive microorganisms: Streptococcus spp. (groups FROM, F, G), Streptococcus viridans;

Aerobic gram-negative microorganisms: Bordetella pertussis, Legionella pneumophila;

Anaerobic microorganisms: Peptostreptococcus species, Prevotella bivia, Clostridium perfringens;

Other: Borrelia burgdorferi, Treponema pallidum, Ureaplasma urealyticum.

Pharmacokinetics:

Absorption - 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 (C_m_Oh) after oral administration of 500 mg is 0.4 mg / l, the time to reach the maximum concentration of the drug in the plasma (TC_m_Oh) 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, 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 intracellular pathogens). It is also transported by phagocytes, polymorphonuclear leukocytes and macrophages. It penetrates the membranes of cells and creates high concentrations in them.

In the focus of inflammation persists in effective concentrations within 5-7 days after taking the last dose. Relationship with plasma proteins - 7 - 50% (inversely proportional to the concentration in the blood). In the liver demethylated, the metabolites formed are inactive. In the metabolism of the drug, 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 % is excreted with bile in unchanged form, 6% by kidneys.

Eating significantly changes the pharmacokinetics: C_m_Oh increases by 31%, the area under the curve "concentration - time" (AUC) does not change.

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

When 1000 mg of azithromycin is taken in patients with mild or moderate renal failure (glomerular filtration rate 10-80 ml / min) C_m_Oh increases by 5.1%, AUC increases by 4.2 %. In patients with severe renal failure (glomerular filtration rate <10 ml / min) C_m_Oh increases by 61%, AUC increases by 35%.

Indications:

Adults and children over 12 years of age or weighing more than 45 kg:

Infectious and inflammatory diseases of the upper and lower respiratory tract caused by sensitive pathogens:

- acute bacterial sinusitis caused by Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae;

- pharyngitis, tonsillitis caused by Streptococcus pyogenes;

- pneumonia caused by atypical pathogens, acute bronchitis;

- bacterial exacerbation of chronic obstructive pulmonary disease caused by Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae;

Infections of the skin and soft tissues (erysipelas, impetigo, secondarily infected dermatoses) caused by Staphylococcus aureus, Streptococcus pyogenes or Streptococcus agalactiae.

Urinary tract infections:

- urethritis, cervicitis caused by Chlamydia trachomatis or Neisseria gonorrhoeae;

- venereal ulcer (chancroid) caused by Haemophilus ducreyi.

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

Contraindications:

- Hypersensitivity (including antibiotics of macrolides and ketolides);

- Severe dysfunction of the liver and / or kidney;

- Children under 12 years of age with a body weight of less than 45 kg (for this dosage form);

- Deficiency of lactase, lactose intolerance, glucose-galactose malabsorption;

- Simultaneous reception with ergotamine and dihydroergotamine.

Carefully:

Arrhythmia (risk of ventricular arrhythmia and lengthening of the interval Q-T), moderate violations of the liver and / or kidney function, joint administration with terfenadine, warfarin, digoxin.

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:

Adults and children over 12 years of age and weighing more than 45 kg, orally, 1 hour before or 2 hours after meals 1 time per day.

Acute bacterial sinusitis, pharyngitis, tonsillitis, pneumonia caused by atypical pathogens, acute bronchitis, bacterial exacerbation of chronic obstructive pulmonary disease - 500 mg / day for one dose for 3 days.

Infections of the skin and soft tissues - 500 mg / day at one time during 3 days. Non-gonococcal urethritis and cervicitis - once 1000 mg (2 tablets).

Gonococcal urethritis and cervicitis - once 2000 mg (4 tablets).

Venereal ulcer (chancroid) - once 1000 mg (2 tablets).

Lyme disease (borreliosis), treatment of stage I (erythema migrans) - 1000 mg (2 tablets) on the first day and 500 mg daily from 2 to 5 days.

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

Side effects:

From the digestive systemnausea, vomiting, diarrhea, abdominal pain / spasms, flatulence, digestive disorders, anorexia, constipation, discoloration of the tongue, pseudomembranous colitis, cholestatic jaundice, hepatitis, changes in laboratory liver function indicators, hepatic insufficiency, liver necrosis (possibly fatal) , pancreatitis, candidiasis of the oral cavity.

From the cardiovascular system: palpitation, arrhythmia, ventricular tachycardia, increased interval QT, bidirectional ventricular tachycardia, hypotension.

From the nervous system: dizziness / vertigo, headache, seizures, drowsiness, paresthesia, asthenia, insomnia, hyperactivity, aggressiveness, anxiety, nervousness.

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

Allergic reactions: itching, skin rashes, angioedema, urticaria, eosinophilia, photosensitivity, anaphylactic reaction, including angioedema (in rare cases, fatal), erythema multiforme, Stevens-Johnson syndrome, Lyell syndrome.

From the musculoskeletal system: arthralgia.

From the blood and lymphatic systems: neutropenia, thrombocytopenia.

From the sense organs: noise in the ears, reversible hearing loss down to deafness (with high doses for a long time), a violation of the perception of taste and smell.

Overdose:

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

Treatment: symptomatic therapy.

Interaction:

Antacids containing aluminum and magnesium, ethanol and food slow down and reduce the absorption of azithromycin. Based on this, azithromycin should be taken 1 hour before meals or 2 hours after meals.

With the joint appointment of azithromycin and warfarin (in usual doses), no changes in prothrombin time have been detected, but considering that macrolide interactions and warfarin may enhance the anticoagulant effect, patients need careful monitoring of prothrombin time.

With the joint administration of digoxin and azithromycin, it is necessary to monitor the level of digoxin in the blood, many macrolides increase absorption of digoxin in the intestine, thereby increasing its concentration in the blood plasma.

It was found that the simultaneous administration of terfenadine and antibiotics of the macrolide class causes arrhythmia and lengthening of the interval QT. Therefore, the aforementioned complications should be considered in the joint administration of terfenadine and azithromycin.

With the joint intake of nelfinavir and azithromycin, the concentration of azithromycin in the serum increases. Correction of a dose of azithromycin is not required. Since it is possible to inhibit the isoenzyme CYP3A4 azithromycin in parenteral form when administered together with cyclosporine, terfenadine, ergot alkaloids, cisapride, pimozide, quinidine, astemizole and other drugs whose metabolism occurs with the participation of this enzyme, the possibility of such interaction in the administration of azithromycin for oral administration should be considered.

Azithromycin has no effect on the pharmacokinetics of theophylline, however, when co-administered with other macrolides theophylline plasma concentrations may be increased.

In the joint use of cyclosporine and azithromycin, it is recommended to monitor the content of cyclosporine in the blood. Despite the fact that there are no data on the effect of azithromycin on the change in the concentration of cyclosporine in the blood, other representatives of the macrolide class are able to change its level in the blood plasma.

Azithromycin does not affect the concentration of atorvastatin, carbamazepine, didanosine, rifabutin, cetirizine and methylprednisolone in the blood in a joint application.

When parenteral application azithromycin does not affect the concentration of cimetidine, efavirenz, fluconazole, indinavir, midazolam, sildenafil, triazolam,trimethoprim / sulfamethoxazole in a joint application. However, the possibility of such interactions in the administration of azithromycin for oral administration should not be ruled out.

With the joint administration of azithromycin and zidovudine, azithromycin does not affect the pharmacokinetic parameters of zidovudine in blood plasma or on the excretion of its and its metabolite glucuronide by the kidneys.

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.

It is necessary to observe a break of 2 hours with simultaneous use of antacids.

After the withdrawal of the treatment, hypersensitivity reactions in some patients may persist, which requires specific therapy under the supervision of a physician.

Cases of pseudomembranous colitis have been described with almost all antibiotics, so this diagnosis should be taken into account in all patients with diarrhea after taking azithromycin.

In the treatment of pharyngitis / tonsillitis caused by Streptococcus pyogenes, as well as for the prevention of acute rheumatic fever, the drug of choice is usually penicillin. Azithromycin is also active against streptococcal infection. In these cases azithromycin, however, is ineffective in preventing the development of acute rheumatic fever.

Azithromycin should not be prescribed in patients with pneumonia who require hospitalization, weakened or elderly patients, or with the following concomitant diseases:

- cystic fibrosis;

- hospital-acquired infections;

- known or suspected bacteraemia;

- also patients with serious diseases that can affect the response of the body to treatment (including immunodeficiency and functional aspension).

Effect on the ability to drive transp. cf. and fur:

Taking the drug in some cases can affect the ability to concentrate and the speed of psychomotor reactions, which can affect the ability to manage vehicles and mechanisms. Therefore, its use immediately before driving and working with mechanisms is not recommended.

Form release / dosage:

Tablets, film-coated 500 mg.

Packaging:

3 tablets in a blister of PVC-aluminum foil. For 1 blister in a cardboard pack together with instructions for use.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the time specified on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-005297/10

Date of registration:08.06.2010

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: & nbsp24.08.2015

Illustrated instructions

Instructions

Tremac-Sanovel (Tremac-Sanovel)