Roxithromycin Sandoz - instructions for use, dose, side effects, contraindications

Tablets 50 mg / 150 mg / 300 mg: active substance: roxithromycin 50.00 mg / 150.00 mg / 300.00 mg; Excipients: cellulose microcrystalline 8.65 mg / 25.95 mg / 51.90 mg, povidone K 30 5.00 mg / 15.00 mg / 30.00 mg, croscarmellose sodium 3.50 mg / 10.50 mg / 21.00 mg, silicon dioxide colloid 2.10 mg / 6.30 mg / 12.60 mg, poloxamer 188 0.05 mg / 0.15 mg / 0.30 mg, magnesium stearate 0.70 mg / 2.10 mg / 4 , 20 mg; film sheath: film coating Opadrai white 5.00 mg / 10.00 mg / 15.00 mg [lactose monohydrate 1.80 mg / 3.60 mg / 5.40 mg, hypromellose 1.40 mg / 2.80 mg / 4.20 mg, titanium dioxide (E171) 1.30 mg / 2.60 mg / 3.90 mg, macrogol 4000 0.50 mg / 1.00 mg / 1.50 mg].

Description:

50 mg tablets: oblong biconvex tablets, covered with a white film membrane, with a risk with oblique margins on both sides.

150 mg tablets: round biconvex tablets, coated with a white film shell, with a risk with bevelled edges on one side and engraving "R 150 "on the other side.

Tablets 300 mg: round biconvex tablets coated with film

shell of white color, with a risk with bevelled edges on one side with engraving "R 300 "on the other side.

Pharmacotherapeutic group:antibiotic-macrolide.

ATX: & nbsp

J.01.F.A Macrolides

J.01.F.A.06 Roxithromycin

Pharmacodynamics:

Roxithromycin is a semisynthetic antibiotic of the macrolide group for oral administration. Has a bacteriostatic effect, is stable in an acidic medium. The mechanism of action is the inhibition of protein synthesis by binding roxithromycin with 50S subunit of ribosomes, thus inhibiting the growth and multiplication of bacteria.

Microorganisms, usually sensitive to the drug: Bordetella pertussis, Moraxella (Branhamella) catarrhalis, Campylobacter coli, Campylobacter jejuni, Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydophila psittaci, Clostridium spp., in t.ch. Clostridium perfringens, Corynebacterium diphtheriae, Legionella pneumophila, Methi-S-Staphylococcus, Mycoplasma pneumoniae, Porphyromonas, Propionibacterium acnes, Rhodococcus equi, Streptococcus pneumoniae, Streptococcus spp, Streptococcus pyogenes.

Microorganisms, moderately sensitive to drug: Ureaplasma urealyticum, Staphylococcus aureus and epidermidis, Borrelia burgdoferi, Gardnerella vaginalis, Neisseria meningitidis, Helicobacter pylori.

Microorganisms resistant to the drug: Acinetobacter spp., Bacteroides fragilis, Enterobacteriaceae, Methi-R Staphylococcus, Pseudomonas spp., Fusobacterium spp., Mycoplasma hominis, Nocardia, Enterococcus spp., Peptostreptococcus spp., Haemophilus influenzae, Vibrio cholerae.

Pharmacokinetics:

Quickly absorbed from the gastrointestinal tract (GIT), the maximum concentration (Cmax) of the drug for a dose of 150 mg in blood plasma is achieved after 2.2 hours and is 6.6 mg / l, for a dose of 300 mg - 9.6 mg / l after 1.5 hours. Application with an interval of 12 hours ensures the preservation of effective concentrations in the blood for 24 hours. When adults use 150 mg of roxithromycin 2 times with an interval of 12 hours, after 24 hours in the blood plasma, therapeutic concentrations are still determined. The equilibrium concentration in plasma with 150 mg twice a day for 10 days is achieved between 2 and 4 days and is 150 mg approximately 9.3 mg / l; at 300 mg twice a day for 11 days - 10.9 mg / l.

It penetrates well into tissues, especially into the lungs (concentration 5,6-3,7 mg / kg), palatine tonsils, prostate gland and uterus. Roxithromycin accumulates in macrophages and polymorphic neutrophilic leukocytes, stimulating their phagocytic activity. Virtually does not penetrate the blood-brain barrier. Penetrates through the placenta, excreted in breast milk. The volume of distribution is 31.2 liters.The association with blood plasma proteins (mainly with alpha-1-glycoprotein, depends on the saturable concentration of the drug), to a lesser extent - with albumins and lipoproteins (does not depend on the saturable concentration of the drug) and is about 80-96% and depends on the plasma concentration of roxithromycin (higher than 4 mg / l).

Metabolized partially in the liver with the participation of the enzymatic system of cytochrome P450, with both inactive and active metabolites secreted with bile.

More than half of the dose of roxithromycin is taken unchanged, mainly through the intestine (more than 50% of the active substance), the rest - kidney (10%), lung (15%). The half-life (T_1/2) is 10.5-14 hours, in children aged 1 month to 13 years - up to 20 hours.

In elderly patients (over 65 years) T_1/2 increases. However, dose adjustment is not required, since the values AUC and C_m_Oh show only a moderate increase after repeated admission when compared with patients of young age.

In patients with severe hepatic insufficiency after ingestion of 150 mg of the drug, an increase in T_1/2up to 25 hours and an increase in the value of C_m_Oh, which may require a dose reduction of 2 times.

In patients with severe renal failure FROM_m_Oh does not differ from that of healthy volunteers.

In children (aged 3 to 12 years) when applied 2.5 mg / kg 2 times a day for 6 days C_m_Oh was achieved after 2 hours and averaged 8.8 μg / ml.

Indications:

Infections caused by microorganisms sensitive to roxithromycin: In adults:

- infection of LOP-organs (acute pharyngitis, tonsillitis, sinusitis);

- infection of the lower respiratory tract (pneumonia (including atypical), bronchitis, bacterial infections in chronic obstructive pulmonary diseases);

- infections of the skin and soft tissues (furunculosis, pyoderma, impetigo, erysipelas in patients with hypersensitivity to beta-lactam antibiotics);

- infections of the urogenital tract (with the exception of gonococcal infections), including urethritis, cervicitis, cervicovaginitis.

Children:

- infection of LOP-organs (acute pharyngitis, tonsillitis, sinusitis);

- infection of the lower respiratory tract (pneumonia (including atypical), bronchitis, bacterial infections in chronic obstructive pulmonary diseases);

- infections of the skin and soft tissues (furunculosis, pyoderma, impetigo, erysipelas in patients with hypersensitivity to beta-lactam antibiotics).

Contraindications:

- increased sensitivity to roxithromycin and other components of the drug;

- increased sensitivity to other antibacterial drugs from the macrolide group;

- simultaneous use of preparations of derivatives of ergotamine and dihydroergotamine;

- simultaneous use with drugs that are substrates CYP3A4 (incl. astemizole, cisapride, pimozide and terfenadine);

- rare hereditary forms of lactose intolerance, lactase deficiency or glucose-galactose malabsorption (since the composition contains lactose);

- children under 4 years of age (for this dosage form);

- pregnancy and the period of breastfeeding.

Carefully:apply the drug in patients with a violation of water-electrolyte balance (hypokalemia, hypomagnesemia); with asthenic bulbar paralysis (myasthenia gravis); with prolongation of the QT interval (congenital syndrome of the extended QT interval, simultaneous use of drugs capable of prolonging the QT interval (for example, antiarrhythmic drugs IA (for example, procainamide) and III classes (for example, amiodarone), tricyclic antidepressants, macrolides, some antifungal drugs (for example, fluconazole), fluoroquinolones (e.g., moxifloxacin), antipsychotics (neuroleptics) (for example, clozapine, risperidone), some antiviral drugs (for example, telaprevir), citalopram)); violation of atrioventricular conduction, arrhythmia, clinically significant bradycardia, clinically significant heart failure; when used simultaneously with colchicine, cyclosporin, theophylline, agonists dopamine stimulants-alkaloids ergot (incl. bromocriptine, cabergoline, lysuride, pergolide); with simultaneous use with warfarin, disopyramide, digoxin; with hepatic insufficiency of severe severity; with renal insufficiency; in elderly patients.

Pregnancy and lactation:

Controlled studies of the use of roxithromycin in pregnant women have not been conducted, so pregnant women roxithromycin is contraindicated.

There are no clinical studies of the use of roxithromycin in lactating women.About 0.05% of the dose of roxithromycin penetrates into breast milk.

If it is necessary to use the drug during lactation, the question of stopping breastfeeding should be resolved.

Dosing and Administration:

Inside, not liquid, squeezed enough water. 15 minutes before meals.

It is necessary to strictly adhere to the regimen and treatment regimen during the whole course of therapy, do not skip the dose and take it at regular intervals. If a dose is missed, take it as soon as possible; Do not take it if it's almost time for the next dose; do not double the dose. To withstand the duration of therapy, especially with streptococcal infections.

Adults: on 150 mg2 times a day. It is possible to use 300 mg once a day.

Children with a body weight of more than 40 kg: 150 mg twice a day.

Mthe highest daily dose for adults and children weighing more than 40 kg is 300 mg

In children weighing less than 40 kg the drug is used depending on the body weight, the type of pathogen and the severity of the infection process.

Children with a body weight of 18-26 kg - 50 mg 2 times a day.

Children with a body weight of 27-40 kg - 100 mg 2 times a day.

With simultaneous renal and hepatic insufficiency It is necessary to monitor the serum concentration of roxithromycin and, if necessary, to carry out dose adjustment.

In elderly patients correction of the dose of roxithromycin is not required (only if there is no decrease in renal function).

In severe hepatic impairment it is necessary to apply 50% of the recommended dose.

With renal insufficiency moderate degree of expression, there is no need to adjust the dose of the drug. In severe renal failure, it is recommended to monitor the plasma concentration of the drug and, if necessary, the dose should be reduced or the interval between administration of the drug is extended.

Duration of drug administration Roxithromycin Sandoz® depends on the indications for use, the severity of the infection process and the activity of the pathogen. The duration of use depends on the indications and severity of the infectious process, should not exceed 10 days. 5 to 10 days for respiratory and ENT diseases; with streptococcal infection - 10 days.

Side effects:According to the World Health Organization (WHO), unwanted effects are classified according to their frequency of development as follows: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, < 1/100), rarely (> 1/10000, <1/1000) and very rarely (<1/10000), including individual messages, the frequency is unknown (can not be calculated from available data).

Infectious and parasitic diseases, infections

frequency is unknown: development of superinfection (with prolonged use), colitis caused by Clostridium difficile (pseudomembranous colitis), fungal infection.

On the part of the blood and lymphatic system infrequently: eosinophilia;

frequency unknown: agranulocytosis, neutropenia, thrombocytopenia.

From the immune system

frequency is unknown: anaphylactic shock.

From the nervous system

often: dizziness, headache;

frequency is unknown: paresthesia, hallucinations, confusion.

From the sense organs

frequency is unknown: transient deafness, taste disorder (dysgeusia), loss of taste, impaired sense of smell, loss of smell (anosmia), decreased hearing, tinnitus, vertigo.

From the side of the cardiovascular system

frequency is unknown: interval lengthening QT, ventricular tachycardia, which can lead to cardiac arrest, incl. by the type of "pirouette".

From the respiratory system frequency is unknown: bronchospasm.

From the gastrointestinal tract

often: nausea, vomiting, dyspepsia, pain in the epigastric abdomen, diarrhea;

frequency is unknown: diarrhea with an admixture of blood, pancreatitis.

From the liver and biliary tract

frequency is unknown: Cholestatic or hepatocellular acute hepatitis.

often: a rash;

infrequently: urticaria, erythema multiforme;

frequency unknown: angioedema, purpura, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Laboratory indicators

frequency unknown: increased activity of "liver" transaminases,

increase in the concentration of alkaline phosphatase in the blood serum.

If any of these side effects are aggravated or you notice

Other side effects not indicated in the instructions, be sure to inform about this to the attending physician.

Overdose:

Symptoms: nausea, vomiting, diarrhea, headache, dizziness. Possible prolongation of the QT interval, as well as increased dose-dependent side effects.

Treatment: symptomatic therapy: gastric lavage no later than 2-3 hours after application of the drug. The specific antidote is unknown. Hemodialysis is not effective.

Interaction:

Contraindicated combinations

The simultaneous use of roxithromycin with eprothrombin and its derivatives contraindicated because it is possible to reduce the perfusion of the tissues of the limbs, which can lead to their necrosis.

Not recommended combinations

When using roxithromycin with drugs, metabolized by isoenzyme CYP3A, such as astemizole, cisapride or pimozide, the plasma concentration of the latter increases and the risk of lengthening the interval increases QT and / or the development of arrhythmia (by the type of "pirouette"). Although roxithromycin weakly inhibits isoenzyme CYP3A, it is impossible to exclude its influence on the metabolism of these drugs. Therefore, in order to avoid the occurrence of fatal side effects, simultaneous use of roxithromycin and astemizole, cisapride or pimozide.

Some macrolides pharmacokinetically interact with terfenadine, leading to an increase in the concentration in the blood plasma of the latter, which can cause the development of ventricular arrhythmia (usually as a "pirouette"). Despite the fact that such a reaction was not demonstrated with the use of roxithromycin and studies with a small amounthealthy volunteers did not reveal the pharmacokinetic interaction of roxithromycin and terfenadine or the corresponding changes in the electrocardiogram (ECG), simultaneous use of drugs is not recommended.

Combinations of drugs that should be used with caution

With the simultaneous use of roxithromycin with drugs that extend the interval QT (eg, antiarrhythmic drugs IA (e.g., procainamide) and III classes (e.g., amiodarone), tricyclic antidepressants, methadone, macrolides, some antifungal agents (fluconazole), fluoroquinolones (moxifloxacin), antipsychotic drugs (neuroleptics) (eg, clozapine, risperidone), some antiviral drugs (telaprevir), citalopram), there may be severe arrhythmias, particularly pirouettes, so caution should be exercised.

Clinically significant interaction of roxithromycin with warfarin not found. There was reported increased prothrombin time and the International Normalized Relationship (MHO) with simultaneous application with antagonists of vitamin K, therefore during the period of treatment it is necessary to control MHO.

Study in vitro showed that roxithromycin can displace disopyramide from the connection with plasma proteins leading to its increase in serum. Therefore, with the simultaneous use of roxithromycin and disopyramide, it is recommended to monitor the ECG, and if possible, the plasma concentration of the latter.

Studies have shown that roxithromycin can increase absorption digoxin. This effect, common to all macrolides, can very rarely lead to intoxication with cardiac glycosides. It can manifest itself with symptoms such as nausea, vomiting, diarrhea, headache and dizziness, a violation of the rhythm of the heart. Therefore, with the simultaneous use of roxithromycin and digoxin (or other cardiac glycoside), it is necessary to monitor the ECG and the plasma concentration of digoxin. The simultaneous use of roxithromycin with inhibitors of hydroxymethylglutaryl-CoA reductase (statins) increases the risk of rhabdomyolysis due to increased plasma concentrations of statins,so use this combination of drugs should be carefully monitored by a doctor.

Roxithromycin increases AUC (area under the concentration-time curve) midazolam an average of 47%, which increases and increases the duration of action midazolam.

Roxithromycin slightly increases the plasma concentration theophylline, that does not require dose adjustment.

Roxithromycin may increase AUC bromocriptine, which can lead to an increased risk of side effects. Roxithromycin increases plasma concentration cyclosporine on 50%.

Roxithromycin may increase plasma concentration rifabutin. In women with concomitant therapy hormonal contraceptives containing estrogen and progesterone, the risk of side effects increases.

There was no clinically significant interaction of roxithromycin with carbamazepine, ranitidine, aluminum hydroxide and magnesium. When used simultaneously with colchicine increased plasma concentrations of colchicine, which may lead to an increased risk of developing its side effects, including nephrotoxic effects.

When used simultaneously with dopamine receptor agonists (incl. bromocriptine, pergolide, lisuride, cabergoline) there was an increase in plasma concentrations of the latter, which may enhance the pharmacodynamic effect and increase the risk of their side effects.

When used simultaneously with cyclosporin there was an increase in plasma concentrations of cyclosporine by 50%, which gradually decreased after stopping roxithromycin.

Special instructions:

With congenital or acquired syndrome of prolonged QT interval, hypokalemia, hypomagnesemia, clinically significant bradycardia, symptomatic heart failure, arrhythmias in anamnesis, the use of roxithromycin is possible only after a rigorous assessment of the risk / benefit ratio.

In case of allergic reactions, the drug should be discontinued. Patients in these cases should be prescribed symptomatic therapy, using antihistamines and glucocorticosteroids.

When treating patients with a drug Roxithromycin Sandoz® should take into account the risk of developing pseudomembranous colitis (caused by Clostridium difficile). If there is a suspicion of pseudomembranous colitis, the use of the drug Roxithromycin Sandoz® should be discontinued immediately and consult a doctor. In this condition, preparations that inhibit peristalsis are contraindicated.

As in the case of other macrolides, roxithromycin can enhance the manifestation of myasthenia gravis.

1 tablet coated with a coating (50, 150 or 300 mg), corresponds to less than 0.01 XE.

Effect on the ability to drive transp. cf. and fur:Data on the adverse effects of the drug Roxithromycin Sandoz® on the ability to drive vehicles and engage in other activities that require concentration and speed of psychomotor reactions, no. In the event of side effects from the nervous system, such as dizziness, hallucinations, one should refrain from driving vehicles or taking other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Tablets, film-coated 50 mg, 150 mg, 300 mg.

Packaging:

Primary packaging

Tablets of 50 and 150 mg:

For 5 or 10 tablets, coated with a film sheath, in PVC / Al. blister.

Tablets of 300 mg:

For 5, 7, 10 or 14 tablets, coated with a film sheath, in PVC / Al. blister.

Secondary packaging

Tablets of 50 and 150 mg:

For 1 or 2 blisters together with instructions for use in a cardboard box.

Tablets of 300 mg:

For 1 or 2 blisters together with instructions for use in a cardboard box.

Special precautions when handling the drug and when destroying an unused medicinal product.

No special precautions are required for destruction unused product.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after expiration of the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N016037 / 01

Date of registration:16.10.2009/24.12.2014

Date of cancellation:2018-02-21

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

S.C. SANDOZ Romania

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp21.02.2018

Illustrated instructions

Instructions

Roxithromycin Sandoz® (Roxithromycin Sandoz®)