Universal reference book for medicines
Name of the preparation: ECOSITRIN ® (ECOZITRIN)

Active substance: clarithromycin

Type: Macrolide antibiotic

Manufacturer: АВВА РУС (Russia)
Composition, form of production and packaging
Tablets covered with a film membrane of
pink color, capsular, biconvex;
Two layers are visible on the cross-section, the inner layer is white or almost white.
1 tab.

clarithromycin 250 mg

Auxiliary substances: lactulose - 300 mg, povidone-K25 - 9.1 mg, magnesium stearate - 6.5 mg, silicon dioxide colloid (aerosil) - 4.33 mg, talc - 13 mg, polacrilin potassium - up to 650 mg.

The composition of the membrane: hypromellose - 9.52 mg, talc - 1.14 mg, titanium dioxide - 5.171 mg, macrogol-4000 - 4.14 mg, dye Azorubin - 0.029 mg.

4 things.
- packings of cellular contour (1) - packs cardboard.
4 things.
- packings cellular planimetric (2) - packs cardboard.
5 pieces.
- packings of cellular contour (1) - packs cardboard.
5 pieces.
- packings cellular planimetric (2) - packs cardboard.
7 pcs.
- packings of cellular contour (1) - packs cardboard.
7 pcs.
- packings cellular planimetric (2) - packs cardboard.
10 pieces.
- packings of cellular contour (1) - packs cardboard.
10 pieces.
- packings cellular planimetric (2) - packs cardboard.
4 things.
- plastic bottles (1) - packs of cardboard.
5 pieces.
- plastic bottles (1) - packs of cardboard.
7 pcs.
- plastic bottles (1) - packs of cardboard.
10 pieces.
- plastic bottles (1) - packs of cardboard.
14 pcs.
- plastic bottles (1) - packs of cardboard.
4 things.
- polymer cans (1) - packs of cardboard.
5 pieces.
- polymer cans (1) - packs of cardboard.
7 pcs.
- polymer cans (1) - packs of cardboard.
10 pieces.
- polymer cans (1) - packs of cardboard.
14 pcs.
- polymer cans (1) - packs of cardboard.
Tablets covered with a film membrane of pink color, capsular, biconvex;
Two layers are visible on the cross-section, the inner layer is white or almost white.
1 tab.

clarithromycin 500 mg

Excipients: lactulose - 600 mg, povidone-K25 - 18.2 mg, magnesium stearate - 13 mg, silicon dioxide colloid (aerosil) - 8.66 mg, talc - 26 mg, polacrilin potassium - up to 1300 mg.

Sheath composition: hypromellose - 14.28 mg, talc - 1.71 mg, titanium dioxide - 7.756 mg, macrogol-4000 - 6.21 mg, dye azorubin - 0.044 mg.

4 things.
- packings of cellular contour (1) - packs cardboard.
4 things.
- packings cellular planimetric (2) - packs cardboard.
5 pieces.
- packings of cellular contour (1) - packs cardboard.
5 pieces.
- packings cellular planimetric (2) - packs cardboard.
7 pcs.
- packings of cellular contour (1) - packs cardboard.
7 pcs.
- packings cellular planimetric (2) - packs cardboard.
10 pieces.
- packings of cellular contour (1) - packs cardboard.
10 pieces.
- packings cellular planimetric (2) - packs cardboard.
4 things.
- plastic bottles (1) - packs of cardboard.
5 pieces.
- plastic bottles (1) - packs of cardboard.
7 pcs.
- plastic bottles (1) - packs of cardboard.
10 pieces.
- plastic bottles (1) - packs of cardboard.
14 pcs.
- plastic bottles (1) - packs of cardboard.
4 things.
- polymer cans (1) - packs of cardboard.
5 pieces.
- polymer cans (1) - packs of cardboard.
7 pcs.
- polymer cans (1) - packs of cardboard.
10 pieces.
- polymer cans (1) - packs of cardboard.
14 pcs.
- polymer cans (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2016.

PHARMACHOLOGIC EFFECT

Semisynthetic antibiotic group of macrolides of broad spectrum of action.
It breaks the synthesis of the protein of microorganisms (binds to the 50S subunit of the microbial cell ribosome membrane). It acts on extracorporeal and intracellular pathogens. The activity of clarithromycin against most of the following microorganisms was proved 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 catarrhalis, Legionella pneumophila; other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae; Mycobacterium: Mycobacterium avium complex (MAC) - complex, including: Mycobacterium avium and Mycobacterium intracellulare; Helicobacter pylori. β-lactamases do not affect the activity of clarithromycin.
Clarithromycin activity in vitro is aerobic Gram-positive microorganisms: Listeria monocytogenes, Streptococcus agalactiae, Streptococci groups C, F, G, Streptococci of the viridans group;
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; Mycobacterium: Mycobacterium leprae, Mycobacterium chelonae, Campylobacterium:Campylobacter jejuni.
The microbiologically active metabolite of clarithromycin-14-hydroxyclarithromycin is twice as active as the parent compound with respect to Haemophilus influenzae.
Clarithromycin and its metabolite in combination can have both additive and synergistic effects on Haemophilus influenzae in vitro and in vivo, depending on the strain of the bacterium.
Most strains of staphylococci resistant to methicillin and oxacillin are resistant to clarithromycin.

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

PHARMACOKINETICS

Suction

Absorption is fast.
Food slows down absorption, without significantly affecting bioavailability. Bioavailability of tablets 250 mg - 50%. After a single reception, 2 peaks of C max are recorded. The second peak is due to the ability of the drug to accumulate in the gallbladder, followed by a gradual or rapid intake into the intestine and absorption. Time to reach C max when taking the drug at a dose of 250 mg - 2-3 hours.
Distribution

Binding to plasma proteins - 65-75%.
In therapeutic concentrations, it accumulates in the lungs, skin and soft tissues (concentrations 10 times higher than antibiotic levels in blood plasma).
With regular administration of a dose of 250 mg / day C ss unchanged drug and its main metabolite - 1 and 0.6 μg / ml, respectively.
When the dose to 500 mg / day Css of the unchanged drug and its metabolite in plasma is increased, 2.7-2.9 and 0.83-0.88 μg / ml, respectively.
Metabolism

After oral administration, 20-30% of the dose is rapidly hydroxylated in the liver with CYP3A4, CYP3A5 and CYP3A7 isoenzymes to form the main metabolite, 14-hydroxyclarithromycin, which has a pronounced antimicrobial activity against Haemophilus influenzae.
It is an inhibitor of the isoenzymes CYP3A4, CYP3A5 and CYP3A7.
Excretion

With regular administration at a dose of 250 mg / day T 1/2 of unchanged drug and its main metabolite is 3-4 and 5-6 hours, respectively.
With an increase in the dose to 500 mg / day T 1/2 of unchanged drug and its metabolite - 4.8-5 and 6.9-8.7 hours, respectively. It is excreted by the kidneys and through the intestine (20-30% - unchanged, the rest - in the form of metabolites). With a single admission in a dose of 250 and 1200 mg, kidneys are allocated 37.9% and 46%, through the intestines - 40.2% and 29.1%, respectively.
Pharmacokinetics in special clinical cases

In case of impaired renal function, there is an increase in TC max , C max and AUC of clarithromycin and its metabolite.

INDICATIONS

Adults:

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 and Mycobacterium intracellulare.

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

For children:

pharyngitis;

- tonsillitis;

- community-acquired pneumonia;

acute sinusitis;

acute otitis media;

uncomplicated infections of the skin and subcutaneous tissue;

- disseminated infection caused by Mycobacterium avium and Mycobacterium intracellulare.

DOSING MODE

The drug is taken orally.
Tablets should be swallowed, not liquid, squeezed with a small amount of liquid.
Adults and children over 12 years of age and weighing more than 33 kg:

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

with acute sinusitis - 500 mg every 12 hours for 14 days;

with exacerbation of chronic bronchitis caused by Haemophilus influenzae - 500 mg every 12 hours for 7-14 days;
caused by Haemophilus parainfluenzae - 500 mg every 12 hours for 7 days; caused by Moraxella catarrhalis , Streptococcus pneumoniae - 250 mg every 12 hours for 7-14 days;
with community-acquired pneumonia caused by Haemophilus influenzae - 250 mg every 12 hours for 7 days;
Streptococcus pneumoniae, Chlamydia pneumoniae, Mycoplasma pneumoniae - 250 mg every 12 hours for 7-14 days;
with uncomplicated skin and subcutaneous tissue infections caused by Staphylococcus aureus, Streptococcus pyogenes - 250 mg every 12 hours for 7-14 days.

To treat and prevent infections caused by Mycobacterium avium, appoint 500 mg 2 times / day.
The maximum daily dose is 1000 mg. Duration of treatment - 6 months or more.
In order to eradicate Helicobacter pylori

Combined treatment with three drugs:

- clarithromycin - 500 mg, lansoprazole - 30 mg and amoxicillin - 1000 mg 2 times / day for 10-14 days;

- clarithromycin - 500 mg, omeprazole - 20 mg and amoxicillin - 1000 mg 2 times / day for 10 days.

Combined treatment with two drugs:

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

For patients with chronic renal insufficiency ( CC less than 30 ml / min or serum creatinine concentration more than 3.3 mg / 100 ml), the dose is reduced 2-fold, or the interval is increased 2-fold.
The maximum duration of treatment in patients of this group is 14 days.
SIDE EFFECT

On the part of the nervous system: headache, dizziness, anxiety, insomnia, nightmares, tremors, convulsions, depression, disorientation, hallucinations, psychosis, depersonalization, confusion, increased myasthenia gravis symptoms, psychotic disorders, paresthesia, mania.

On the part of the digestive system: anorexia, anorexia, appetite, nausea, eructation, vomiting, flatulence, gastritis, gastralgia, diarrhea, stomatitis, glossitis, candidiasis of the oral mucosa, discoloration of the tongue and teeth, dryness of the oral mucosa, acute pancreatitis, activity of hepatic transaminases, cholestasis, hepatocellular and cholestatic hepatitis, cholestatic jaundice;
rarely - pseudomembranous colitis, hepatic insufficiency with a lethal outcome, mainly on the background of severe comorbidities and / or concomitant drug therapy, dyspepsia, constipation.
From the cardiovascular system: ventricular tachycardia, incl.
such as "pirouette", flutter and fibrillation of the ventricles, increase intrevala QT on the ECG.
From the senses: noise, ringing in the ears, vertigo, taste change (dysgeusia), agevia;
in isolated cases - hearing loss that occurs after the drug is discontinued, an olfactory impairment, anosmia.
From the skin and soft tissues: erythrasma, acne, erysipelas.

From the musculoskeletal system: myalgia, myopathy, pain in the chest.

From the hemopoiesis: rarely - thrombocytopenia, (unusual bleeding, hemorrhage), agranulocytosis, thrombocytosis, prolongation of prothrombin time, increase in INR level.

From the side of the urinary system: interstitial nephritis, kidney failure.

Laboratory indicators: leukopenia, neutropenia, eosinophilia, increased bilirubin concentration in the blood, hypercreatininaemia, hypoglycemia (including with the simultaneous use of hypoglycemic drugs), a change in the color of urine.

Allergic reactions: skin rash, itching, urticaria, skin hyperemia, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis, anaphylactic reactions, rash with eosinophilia and systemic symptomatology (DRESS-syndrome), purpura Shenlaine-Henoch, hemorrhage.

Other: secondary infections (development of resistance of microorganisms), intense sweating, malaise, asthenia, chills, fatigue.

CONTRAINDICATIONS

- Hypersensitivity to clarithromycin, other antibiotics of the macrolide group, other components of the drug;

- severe hepatic insufficiency, which occurs simultaneously with renal insufficiency;

- porphyria;

- hypokalemia;

- simultaneous administration of cisapride, astemizole, pimozide, terfenadine, ergotamine and other ergot alkaloids;

- simultaneous use with lovastatin and simvastatin, with midazolam for oral administration, with colchicine in patients with impaired renal or hepatic function, taking P-glycoprotein inhibitors or potent inhibitors of the CYP3A4 isoenzyme;

- the presence in patients of prolongation of the QT interval in the history, ventricular arrhythmia or ventricular tachycardia of the "pirouette" type;

- Cholestatic jaundice / hepatitis, caused by the use of clarithromycin (in the anamnesis);

- Children under 12 years of age (for this dosage form);

- the period of lactation (breastfeeding);

- lactose intolerance or lactase deficiency, as well as glucose-galactose malabsorption.

Carefully:

- renal failure of moderate to severe severity;

- hepatic insufficiency of moderate and severe degree;

- Myasthenia gravis;

- simultaneous use with drugs, inducing and metabolizing isoenzyme CYP3A4, benzodiazepines (alprazolam, triazolam, midazolam for IV application), antiarrhythmic drugs of class IA and III, blockers of slow calcium channels, which are metabolized by isoenzyme CYP3A4;

- IHD;

- severe heart failure;

- hypomagnesemia;

pronounced bradycardia.

PREGNANCY AND LACTATION

The safety of clarithromycin during pregnancy is not established.
In pregnancy, especially in the first trimester, it is recommended to prescribe clarithromycin if the benefit from its administration exceeds the potential risk to the fetus and / or there is no safer therapy with alternative drugs. If the pregnancy occurred while taking the drug, the patient should be warned about the possible risk to the fetus.
If it is necessary to prescribe the drug during lactation, the question of abolishing breastfeeding should be resolved.

APPLICATION FOR FUNCTIONS OF THE LIVER

Caution is prescribed for renal failure of moderate to severe severity.

APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Caution is prescribed for hepatic insufficiency of moderate to severe severity.

Contraindicated use of the drug in severe hepatic insufficiency, which occurs simultaneously with renal failure.

APPLICATION FOR CHILDREN

Contraindicated use of this dosage form in children under 12 years of age.

SPECIAL INSTRUCTIONS

In the presence of chronic liver disease, it is necessary to regularly monitor the activity of enzymes in the blood serum.

With caution appoint the drug on the background of therapy with 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 anticoagulants, prothrombin time and INR should be monitored.

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

If a severe diarrhea occurs during or after treatment, the diagnosis of pseudomembranous colitis should be deleted, which requires immediate discontinuation of the drug and the appointment of appropriate treatment.

Before using the drug, a sensitivity test should be performed in the development of resistance of Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus pyogenes to antibiotics of the macrolide group.
It is possible to develop cross-resistance to clarithromycin and other antibiotics of the macrolide group.With prolonged use of the drug, the development of superinfection is possible.
The drug should be used with caution in patients with a predisposition to lengthen the QT interval.

In patients with IHD, severe heart failure, hypomagnesemia, severe bradycardia, taking clarithromycin, and also with simultaneous use with class IA antiarrhythmics (quinidine, procainamide) and III (dofetilide, amiodarone, sotalol), the electrocardiogram should be monitored regularly to increase of the QT interval.

Against the background of the drug can be observed the development of pseudomembranous colitis, aggravation of the symptoms of myasthenia gravis.

With the use of clarithromycin, there was reported a violation of liver function (increased hepatic transaminase activity of hepatocellular and / or cholestatic hepatitis with jaundice or without).
Dysfunction of the liver can be severe, but usually are reversible. There are reports of cases of hepatic insufficiency with a fatal outcome, mainly associated with the presence of serious concomitant diseases and / or simultaneous use of other medications. When signs and symptoms of hepatitis such as anorexia, jaundice, darkening of the urine, itching, tenderness of the abdomen during palpation, it is necessary to immediately stop the treatment with clarithromycin.In the presence of chronic liver diseases it is necessary to carry out regular monitoring of serum enzymes.
If hypersensitivity reactions occur, the drug should be discarded.

OVERDOSE

Symptoms: abdominal pain, nausea, vomiting, diarrhea.

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

With the simultaneous administration of clarithromycin and drugs primarily metabolized by the CYP3A isoenzyme, a mutual increase in their concentrations is possible, which may enhance or prolong both the therapeutic and side effects.
Contraindicated joint administration with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, as well as with lovastatin and simvastatin.
Drugs that are inducers of CYP3A (eg, phenobarbital and St. John's wort) can induce the metabolism of clarithromycin.
This can lead to a subtherapeutic level of clarithromycin and to a decrease in its effectiveness.
Assign with caution to carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants (including warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine, as well as phenytoin, theophylline and valproic acid (metabolized through other isoenzymes of cytochrome P450).

Apply with caution with alprazolam, triazalam, midazalam for iv administration.
It is necessary to correct the dose of the drug and monitor the concentration in the blood.
When combined with cisapride, pimozide, terfenadine and astemizole, it is possible to increase the concentration of the latter in the blood, increase the QT interval, the occurrence of arrhythmia, including ventricular tachycardia, including.
type "pirouette" and ventricular fibrillation.
When combined with ergotamine and dihydroergotamine, acute poisoning with drugs of the ergotamine group (vascular spasm, limb and other tissue ischemia including CNS) is possible.

Efavirenz, nevirapine, rifampicin, rifabutin and rifapentin (cytochrome P450 inducers) reduce the level of clarithromycin in the plasma and weaken the therapeutic effect of the latter, while increasing the concentration of 14-hydroxyclarithromycin.

With the simultaneous administration of fluconazole at a dose of 200 mg daily and clarithromycin at a dose of 1 g / day, an increase in C ss and AUC of clarithromycin is possible by 33% and 18%, respectively.
Correction of the dose of clarithromycin is not required.
With the simultaneous use of ritonavir 600 mg / day and clarithromycin at a dose of 1 g / day, a decrease in the metabolism of clarithromycin is possible (C maxincrease by 31%, C ss by 182% and AUC by 77%), complete suppression of 14-hydroxyclarithromycin formation.
In patients with chronic renal insufficiency, dose adjustments are necessary: ​​with a QC of 30-60 ml / min, the dose of clarithromycin should be reduced by 50%, with a QC of less than 30 ml / min - by 75%. Ritonavir should not be taken with clarithromycin in a dose exceeding 1 g / day.
When combined with quinidine and disopyramide, there may be a ventricular tachycardia such as pirouette.
It requires ECG monitoring (increasing the QT interval), serum concentrations of these drugs.
Clarithromycin increases the concentrations of HMG-CoA reductase inhibitors (lovastatin, simvastatin).
Perhaps the development of rhabdomyolysis in patients taking these drugs together.
In the application of omeprazole and clarithromycin may increase C max , AUC, and T 1/2 of omeprazole is 30%, 89% and 34% respectively. The average pH in the stomach within 24 hours was 5.2 when receiving only omeprazole and omeprazole 5.7 when taking in conjunction with clarithromycin.
In the application of clarithromycin and anticoagulants may increase the action of the latter. While the use of warfarin and other indirect anticoagulants is necessary to monitor the INR and prothrombin time.
In the application of clarithromycin with sildenafil, tadalafil or vardenafil (PDE5 inhibitors) may increase the inhibitory effect on phosphodiesterase may require reduction in the dose of sildenafil, tadalafil and vardenafil.
If concomitant use of clarithromycin with theophylline and carbamazepine, may increase the concentration of the latter in the systemic circulation.
In the application of clarithromycin with tolterodine in patients with a low level of metabolism by CYP2D6 may require dose reduction in the presence of tolterodine clarithromycin (SYP3A inhibitor).
When co-administered clarithromycin (1 g / day) with midazolam (p.o.) may be increased midazolam AUC 7 times. In applying midazolam (w / w) and clarithromycin may require a dosage adjustment. The same precautions should also apply to other benzodiazepines that are metabolized by CYP3A. For benzodiazepines, which is independent of the inference SYP3A (temazepam, nitrazepam, lorazepam), it is unlikely clinically significant interaction with clarithromycin.
When co-administered with clarithromycin colchicine may increase the action of colchicine. Necessary to monitor the possible development of the clinical symptoms of colchicine toxicity, especially in elderly patients and patients with chronic renal failure (reported fatal cases).
When co-administered clarithromycin and digoxin should be carefully monitored in the serum concentration of digoxin (may increase its concentration and the development of potentially lethal arrhythmias).
Simultaneous administration of clarithromycin and zidovudine adult HIV-infected patients may lead to a reduction in C sszidovudine. Requires selection of doses of clarithromycin and zidovudine. This type of interaction does not occur in HIV-infected children receiving clarithromycin in suspension together with zidovudine.
When co-administered clarithromycin (1 g / day) and atazanavir (400 mg / day) may increase AUC by 28% atazanavir, clarithromycin - 2 times, decrease AUC hydroxyclarithromycin 14 to 70%. In patients with CC 30-60 ml / min clarithromycin dose should be reduced by 50%. Clarithromycin at doses in excess of 1 g / day, should not be administered in conjunction with protease inhibitors.
When co-administered clarithromycin and itraconazole may increase the mutual concentrations of drug in plasma. For patients receiving both itraconazole and clarithromycin, should be carefully monitored because of the possible amplification or elongation of the pharmacological effects of these drugs.
When simultaneous administration of clarithromycin (1 g / day) and saquinavir (soft gelatin capsules of 1200 mg 3 times / day) may be increased AUC and C sssaquinavir 177% and 187%, respectively, and 40% of clarithromycin. When co-administration of these two drugs for a limited time in doses / dosage forms listed above, the dose correction is not required.
When co-administered with verapamil may decrease blood pressure, bradyarrhythmias and lactic acidosis.
With simultaneous use of clarithromycin and oral hypoglycemic agents, including Insulin, in rare cases may develop hypoglycaemia. It recommended careful monitoring of blood glucose levels.
Together with the admission clarithromycin (500 mg, 2 times / day) etravirine reduces the concentration of clarithromycin in plasma by 53% and increases the concentration of the active metabolite, a 14-hydroxyclarithromycin, 46%. Since 14- hydroxyclarithromycin has reduced activity against Mycobacterium avium complex (MAC), overall activity and its metabolite klaritromitsiia against this pathogen may change.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

The drug should be stored in a dry, protected from light, out of reach of children at a temperature of no higher than 25 ° C.
Shelf life - 3 years.
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