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

Excipients: carbopol 75 mg, povidone K-90 17.5 mg, hypromellose phthalate 152.1 mg, castor oil 16.1 mg, silicon dioxide colloid 5 mg, sucrose 2748.3 mg, xanthan gum 3.8 mg, tutti-frutti flavor 35.7 mg, potassium sorbate 20 mg, citric acid 4.2 mg, titanium dioxide 35.7 mg, maltodextrin 285.7 mg.

250 mg / 5 ml:

active substance: clarithromycin 250 mg;

Excipients: carbopol 150 mg, povidone K-90 32 mg, hypromellose phthalate 302.4 mg, castor oil 32 mg, silicon colloidal dioxide 10 mg, sucrose 2535.16 mg, xanthan gum 3.8 mg, tutti frutti flavor 35.7 mg , potassium sorbate 20 mg, citric acid 4.24 mg, titanium dioxide 35.7 mg, maltodextrin 238.1 mg.

Description:

Granules from white with a yellowish tint to white with a light brown tint of color with a slight characteristic smell of flavor.After dissolution in water - a suspension of almost white color with a light brown tinge with a slight characteristic smell of flavor.

Pharmacotherapeutic group:antibiotic-macrolide

ATX: & nbsp

J.01.F.A.09 Clarithromycin

Pharmacodynamics:

Clarithromycin is a semisynthetic macrolide antibiotic with a broad spectrum of action. In sensitive microorganisms, by contacting 50S subunit of ribosome membrane, violates protein synthesis. It acts on extracorporeal and intracellular pathogens. The nature of the antimicrobial effect of clarithromycin is predominantly bacteriostatic.

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

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

- aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella (Branhamella) catarrhalis, Legionella pneumophila;

- other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae;

- mycobacteria: Mycobacterium avium complex (MAC), a complex including: Mycobacterium avium and Mycobacterium intracellulare, Helicobacter pylori.

Activity of clarithromycin in vitro:

- aerobic Gram-positive microorganisms: Listeria monocytogenes, Streptococcus agalactiae, Streptococcus spp. group of viridans, Streptococci group C, F, G;

- aerobic gram-negative microorganisms: Neisseria gonorrhoeae, Bordetella pertussis, Pasteurella multocida;

- anaerobic Gram-positive microorganisms: Clostridium perfringens, Peptococcus niger, Propionibacterium acnes;

- anaerobic gram-negative microorganisms: Bacteroides melaninogenicus;

- Spirochetes: Borrelia burgdorferi, Treponema pallidum;

- mycobacteria: Mycobacterium leprae, Mycobacterium chelonae;

- Campylobacteria: Campylobacter jejuni.

Beta-lactamases do not affect the activity of clarithromycin.

Most strains of staphylococci, resistant to the effects of methicillin and oxacillin, are resistant to the action of clarithromycin.

It is possible to develop cross-resistance to clarithromycin and other antibiotics of the macrolide group, as well as lincomycin and clindamycin.

The microbiologically active metabolite of clarithromycin-14 (R) -hydroxyclarithromycin is twice as active as clarithromycin towards Haemophilus influenzae.

Clarithromycin and its metabolite in combination, depending on the bacterial strain, can have both additive and synergistic effects on Haemophilus influenzae in vitro and in vivo.

Pharmacokinetics:

Suction and distribution. TOlarithromycin when ingested quickly and well absorbed. The biological availability of the suspension is 50% or higher. The connection with plasma proteins is 65-75%.Eating directly before taking the drug slows the absorption of clarithromycin, but does not affect its bioavailability. In this way, clarithromycin can be administered regardless of food intake.

With a regular intake of 250 mg per day, the equilibrium concentration (Css) of clarithromycin and its main metabolite (14-hydroxyclarithromycin) is 1 μg / ml and 0.6 μg / ml, respectively. Time to reach the maximum concentration (TC_max) when taking 250 mg of the drug is 2-3 hours. When the drug is administered at a dosage of 500 mg per day, the Css of clarithromycin and its metabolite in the plasma averages 2.7-2.9 μg / ml and 0.83-0.88 μg / ml, respectively.

In therapeutic concentrations, it accumulates in the lungs, skin and soft tissues (concentrations 10 times higher than serum).

Metabolism and excretion. After oral administration, 20-30% of the dose is rapidly hydroxylated in the liver by cytochrome P450 isoenzymes: CYP3A4, CYP3A5 and CYP3A7 with formation of the main metabolite - 14 (R) -hydroxyclamirithromycin, which has a pronounced antimicrobial activity against Haemophilus influenzae. Is an inhibitor of isoenzymes CYP3A4, CYP3A5 and CYP3A7.

The half-life (T_1/2) clarithromycin with the intake of 250 mg of the drug is 3-4 hours and its metabolite 5-6 hours; when taking 500 mg of T_1/2of the starting compound is increased to 4.8-5 hours and for 14-hydroxycyl-rhythomycin this value is 6.9-8.7 hours. When administered by clarithromycin, 20-30% of the dose taken is excreted unchanged, the rest - in the form of metabolites . In healthy people, after taking a single dose of clarithromycin, 250 mg of 37.9% of the accepted dose is excreted from the body by the kidneys, 40.2% through the intestine.

With chronic renal failure, the maximum concentration increases (C_mOh), TS_mOh and the area under the "concentration-time" curve (AUC) clarithromycin and its metabolite.

Indications:

Children under 12 years of age or weighing less than 33 kg:

- pharyngitis, tonsillitis, community-acquired pneumonia, acute sinusitis, acute otitis media, uncomplicated infections of the skin and subcutaneous tissue;

- disseminated infection caused by Mycobacterium avium, Mycobacterium intracellulare.

Adults and children from 12 years old or with a body weight of more than 33 kg:

- pharyngitis, tonsillitis, acute sinusitis, exacerbation of chronic bronchitis, community-acquired pneumonia, uncomplicated infections of the skin and subcutaneous tissue;

disseminated infection caused by Mycobacterium avium, Mycobacterium intracellulare;

- in combination with amoxicillin and omeprazole / lansoprazole in the form of triple therapy for infections caused by Helicobacter pylori, including duodenal ulcer;

- in combination with omeprazole or ranitidine bismuth citrate in the form of dual therapy for the treatment of duodenal ulcers caused by Helicobacter pylori.

Contraindications:

Hypersensitivity, porphyria, pregnancy, lactation, deficiency, sugarase / isomaltase, fructose intolerance, glucose-galactose malabsorption.

Simultaneous reception of astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, lovastatin, simvastatin, alprazolam, midazolam for oral administration, triazolam.

Children up to 6 months of age (for this dosage form).

Carefully:

Renal and / or hepatic insufficiency, myasthenia gravis " gravis, simultaneous reception of drugs metabolized in the liver, simultaneous reception of colchicine.

Pregnancy and lactation:

The safety of clarithromycin in pregnant and lactating women has not been studied.

Clarithromycin is not prescribed in pregnancy, except when the expected benefit to the mother exceeds the potential risk to the fetus in the absence of safer alternative therapies.If the pregnancy occurred during the period of treatment with this drug, the patient should be notified of the potential risk to the fetus.

Clarithromycin is excreted in breast milk, so when using it, breastfeeding should be stopped.

Dosing and Administration:

Inside, regardless of food intake.

Children under 12 years of age or weighing less than 33 kg

Non-mycobacterial infections

The recommended daily dose of clarithromycin suspension for children is 7.5 mg / kg twice daily. The interval between doses should be 12 hours.

Duration of treatment 5-10 days, depending on the pathogen and severity disease.

Depending on the weight of the child, the following dosage regimens are recommended:

Body weight * (kg)_;	Doses, a teaspoonful (5 ml) 2 times a day
Body weight * (kg)_;	125 mg / 5ml	250 mg / 5 ml
8-11	0,5	-
12-19	1	0,5
20 - 29	1,5	0,75
30-40	2	1

* For children weighing less than 8 kg, the dose is selected by body weight (approximately 7.5 mg / kg twice daily).

Mycobacterial infections

It is recommended to take 7.5 mg / kg every 12 hours, to 500 mg twice a day. The maximum daily dose is 1000 mg. Duration of treatment 6 months or more.

Adults and children from 12 years old or with a body weight of more than 33 kg

The dose is selected by the doctor individually, based on the following dosages:

- with pharyngitis and tonsillitis caused by Streptococcus pyogenes: 250 mg daily for 10 days every 12 hours;

- at an acute genyantritis: 500 mg for 14 days every 12 hours;

- with exacerbation of chronic bronchitis caused by Haemophilus influenzae: for 500 mg for 7-14 days every 12 hours caused by Haemophilus parainfluenzae: on 500 mg in for 7 days every 12 hours, caused by Moraxella catarrhalis, Streptococcus pneumoniae: 250 mg for 7-14 days every 12 hours;

- in community-acquired pneumonia caused by Haemophilus influenzae: 250 mg for 7 days every 12 hours caused by Streptococcus' pneumoniae, Chlamydia pneumoniae, Mycoplasma pneumoniae: Po 250 mg for 7-14 days every 12 hours;

- with uncomplicated infections of the skin and subcutaneous tissue caused by Staphylococcus aureus, Streptococcus pyogenes: by 250 mg for 7-14 days every 12 hours.

To treat infections caused by the complex of Mycobacterium avium (MAC)

Inside for 500 mg 2 times a day. Duration of treatment - 6 months or more.

Adults with a view to eradicating Helicobacter pylori

Combined treatment with three drugs:

- clarithromycin 500 mg twice a day in combination with lansoprazole 30 mg twice a day and amoxicillin 1000 mg twice a day for 10-14 days;

- clarithromycin 500 mg twice a day in combination with amoxicillin 1000 mg twice a day and omeprazole 20 mg twice a day for 10 days.

Combined treatment with two drugs:

- clarithromycin 500 mg 3 times daily in combination with omeprazole at a dose of 40 mg / day for 14 days with the appointment of omeprazole for the next 14 days at a dose of 20 mg / day.

In adults and children with chronic renal insufficiency, in which the creatinine clearance is less than 30 ml / min or the serum creatinine concentration is more than 3.3 mg / 100 ml, the dose is reduced by 2 times, or the interval is increased by a factor of 2. In such cases, the maximum duration of treatment should not exceed 14 days.

Preparation of the suspension: in a vial of granules, add water from a plastic container and shake until a homogeneous suspension is obtained. Shake well before use

For accurate dose metering a measuring syringe is attached to the vial.

Using measuring syringe

1. Shake the suspension well.

2. Insert the syringe tightly into the neck of the vial.

3. Gently pull the piston upward, gaining the suspension in the syringe to the desired mark.

4. Remove the syringe.

5. Place the syringe in the mouth of the Rebeand slowly press the piston, gradually releasing the slurry.

6. After use, wash the syringe in warm water and dry it out of reach of child's place.

Side effects:

From the nervous system: headache, dizziness, anxiety, insomnia, "nightmarish" dreams, convulsions, depression, disorientation, hallucinations, psychosis, depersonalization, confusion.

From the digestive system: dyspepsia, nausea, vomiting, gastralgia, diarrhea, stomatitis, glossitis, candidiasis of the oral mucosa, discoloration of the tongue and teeth, acute pancreatitis, increased activity of "liver" transaminases, hepatocellular and cholestatic hepatitis, cholestatic jaundice; rarely - pseudomembranous colitis, hepatic insufficiency with a lethal outcome mainly on the background of severe co-morbidities and / or concomitant drug therapy.

From the side of the cardiovascular system: ventricular tachycardia, incl. type "pirouette", flutter and fibrillation of the ventricles, increasing the interval QT on an electrocardiogram (ECG).

From the sense organs: noise, ringing in the ears, change in taste (dysgeusia); in isolated cases - hearing loss, which occurs after the drug is discontinued, impaired sense of smell.

On the part of the organs of hematopoiesis and the system of hemostasis: rarely - thrombocytopenia (unusual bleeding, hemorrhage).

From the side of the urinary system: interstitial nephritis.

From the musculoskeletal system: myalgia, arthralgia.

Laboratory indicators: leukopenia, hypercreatininaemia, hypoglycemia (incl.with the simultaneous administration of hypoglycemic drugs), neutropenia.

Allergic reactions: skin rash, itching, urticaria, skin hyperemia, malignant - exudative erythema (Stevens-Johnson syndrome), toxic epidermal - necrolysis, angioedema and other anaphylactic reactions.

Other: secondary infections (development of resistance of microorganisms), tremor, anorexia.

Overdose:

Symptoms: abdominal pain, nausea, vomiting, diarrhea.

Treatment: gastric lavage, maintenance therapy. It is not removed during hemo- or peritoneal dialysis.

Interaction:

When taking clarithromycin simultaneously with drugs, primarily metabolized isoenzymes CYP3A, there may be a mutual increase in their concentrations, which can enhance and prolong therapeutic and side effects. Contraindicated joint administration with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, alprazolam, midazolam, triazolam, lovastatin, simvastatin.

Take with caution in conjunction with carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants (incl.warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine, as well as phenytoin, theophylline and valproic acid (metabolized through other isoenzymes of cytochrome P450). At the same time, it is necessary to correct the dose of drugs and monitor their concentration in the blood.

When co-administered with terfenadine, cisapride, pimozide and astemizole, it is possible to increase the concentration of the latter in the blood and increase the interval QT, the occurrence of arrhythmia, including ventricular tachycardia, including "pirouette" type, and ventricular fibrillation.

With the combined use of clarithromycin with ergotamine and dihydroergotamine, acute poisoning with drugs of the ergotamine group is possible, manifested by vasospasm, ischemia of limbs and other tissues, including the central nervous system.

Efavirenz, nevirapine, rifampicin, rifabutin and rifapentin, being inducers of the cytochrome P450 system, reduce the concentration of clarithromycin in the plasma and weaken its therapeutic effect, and at the same time increase the concentration of erythromycin 14-hydroxycil.

With the simultaneous administration of clarithromycin (1 g / day) and fluconazole (200 mg daily), an increase Css and AUC clarithromycin by 33% and 18%, respectively, while correction of the dose of clarithromycin is not required.

With the simultaneous use of clarithromycin (1 g / day) and ritonavir (600 mg / day), a decrease in the metabolism of clarithromycin (an increase in C_mOh by 31%, the minimum Css by 182% and AUC on 77%), complete suppression of the metabolite - 14-hydroxyclatromycin. Correction of the dose of clarithromycin in these cases is not required for patients with normal renal function. However, in patients with creatinine clearance from 30 to 60 ml / min, the dose of clarithromycin should be reduced by 50%. When creatinine clearance is less than 30 ml / min, the dose of clarithromycin should be reduced by 75%.

With simultaneous treatment with ritonavir should not be prescribed clarithromycin in a dose exceeding 1 g / day.

When combined with quinidine and disopyramide, there may be a ventricular tachycardia such as pirouette. It is necessary to monitor the ECG (increase in the QT interval) and serum concentrations of these drugs.

Clarithromycin increases the concentrations of inhibitors of hydroxymethylglutaryl-CoA reductase (lovastatin and simvastatin) - possibly the development of rhabdomyolysis.

With the simultaneous use of clarithromycin and omeprazole, an increase in C_mOh, AUC and T_1/2omeprazole by 30%, 89% and 34%, respectively. The average pH value in the stomach for 24 hours with the simultaneous intake of omeprazole and clarithromycin was 5.7, and when taking omeprazole alone, it was 5.2.

With the joint reception of clarithromycin with indirect anticoagulants, the effect of the latter increases.

With the combined use of clarithromycin with sildenafil, tadalafil or vardenafil, which are inhibitors of phosphodiesterase-5, it is possible to increase the inhibitory effect on phosphodiesterase, and a dose reduction of phosphodiesterase-5 inhibitors may be required.

With the simultaneous use of clarithromycin with theophylline and carbamazepine, there is an increase in the concentration in the systemic circulation of the latter.

With the simultaneous use of clarithromycin with tolterodine in patients with slow metabolism via the CYP2D6 isoenzyme, a dose reduction of tolterodine in the presence of clarithromycin (inhibitor of CYP3 A isoenzymes) may be required.

With the simultaneous administration of clarithromycin (1 g / day) with midazolam (oral), an increase AUC the last in 7 times.It is necessary to avoid the combined oral administration of clarithromycin and midazolam and other benzodiazepines, which are metabolized by isoenzymes CYP3A (triazolam and alprazolam).

With the simultaneous use of midazolam (IV) and clarithromycin, a dose adjustment may be required. The same precautions should be applied to other benzodiazepines, which are metabolized by isoenzymes CYP3A.

For benzodiazepines, the excretion of which does not depend on isoenzymes CYP3A (temazepam, nitrazepam, lorazepam), clinically significant interaction with clarithromycin is unlikely.

When co-administered with clarithromycin and colchicine, colchicine may be enhanced. It is necessary to monitor the possible development of clinical symptoms of colchicine intoxication, especially in elderly patients and patients with chronic renal failure (reported fatal cases).

When the combined use of clarithromycin and digoxin is necessary to constantly monitor the concentration of digoxin in the serum, tk. it is possible to increase its concentration and develop potentially lethal arrhythmias.

The simultaneous use of zidovudine in HIV-infected adults and clarithromycin may lead to a decrease Css zidovudine. It is necessary to select doses of clarithromycin and zidovudine.

With the joint administration of clarithromycin (1 g / day) and atazanavir (400 mg / day) is possible.

enlargement AUC atazanavir by 28%, clarithromycin by 2 times, decrease AUC 14-hydroxyclarithromycin by 70%. In patients with creatinine clearance from 30 to 60 ml / min, the dose of clarithromycin should be reduced by 50%.

When treating protease inhibitors, do not simultaneously apply clarithromycin in doses over 1 g / day.

With the simultaneous use of clarithromycin and itraconazole, an increase in the concentrations of clarithromycin and itraconazole in plasma is possible. Careful monitoring of patients simultaneously taking itraconazole and clarithromycin, because of the possibility of enhancing or prolonging the duration of the pharmacological effects of these drugs.

With concurrent administration of clarithromycin (1 g / day) and saquinavir (1200 mg 3 times daily, soft gelatin capsules), there is an increase AUC and Css saquinavir by 177% and 187%, respectively, and clarithromycin by 40%.When these two medicines are used together for a limited time, in the doses and dosage forms mentioned above, dose adjustment is not required.

With a joint admission with verapamil possible lowering of blood pressure, bradyarrhythmia and lactic acidosis.

With the joint appointment of clarithromycin and ranitidine bismuth citrate clarithromycin increases the absorption of the latter. The concentration of clarithromycin in plasma does not change when combined with ranitidine bismuth citrate.

Special instructions:

In the presence of chronic liver diseases it is necessary to conduct regular monitoring of the activity of serum enzymes.

Caution is prescribed against the background of drugs metabolized by the liver (it is recommended to measure their concentration in the blood).

In the case of co-administration with warfarin or other indirect anticoagulants, prothrombin time should be monitored.

If severe and prolonged diarrhea occurs during or after treatment, pseudomembranous colitis should be excluded, which requires immediate discontinuation of the drug and the appropriate treatment.

When developing a secondary infection, adequate therapy should be prescribed.

Effect on the ability to drive transp. cf. and fur:In recommended doses, the drug does not affect the speed of psychomotor reactions and concentration of attention.

Form release / dosage:

Granules for the preparation of the suspension for ingestion 125 mg / 5 ml, 250 mg / 5 ml.

Packaging:

125 mg / 5ml: a bottle of dark glass with a capacity of 70 ml with a plastic lid complete with a solvent - purified water (plastic containers) 37 ml, a syringe dosing into a cardboard box together with instructions for use.

250 mg / 5 ml: a bottle of dark glass with a capacity of 50 ml with a plastic lid in

complete with a solvent - purified water (plastic containers) 26 ml, a syringe dosing into a cardboard box together with instructions for use.

250 mg / 5 ml: a bottle of dark glass with a capacity of 100 ml with a plastic lid complete with a solvent - purified water (plastic containers) 52 ml, a syringe dosing into a cardboard box together with instructions for use.

Storage conditions:

Granules for the preparation of a suspension for ingestion 125 mg / 5 ml, 250 mg / 5 ml: in dry, 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.

Prepared slurry: at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Solvent - 5 years.

The finished suspension is 14 days.

Do not use after the time specified on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001248

Date of registration:21.11.2011

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: & nbspMEDEX-Consult Ltd.MEDEX-Consult Ltd.Russia

Information update date: & nbsp21.11.2011

Illustrated instructions

Instructions

Seydon-Sanovel (Seidon-Sanovel)