Ekozitrin

General characteristics. Structure:

Active agent: кларитромицин 250 mg

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

Structure of a cover: (a gipromelloza - 9.52 mg, talc - 1.14 mg, titanium dioxide - 5.171 mg, a macrogoal of 4000 - 4.14 mg, dye an azoruby - 0.029 mg) - to 670 mg.

Active agent: кларитромицин 500 mg

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

Structure of a cover: (a gipromelloza - 14.28 mg, talc - 1.71 mg, titanium dioxide - 7.756 mg, a macrogoal of 4000 - 6.21 mg, dye an azoruby - 0.044 mg) - to 1330 mg.

Pharmacological properties:

Semi-synthetic makrolidny antibiotic of a broad spectrum of activity. Breaks synthesis of protein of microorganisms (communicates with 50S in subunit of a membrane of ribosomes of a microbic cell). Works on out of - and intracellularly located activators. Activity of a klaritromitsin concerning the majority of the following microorganisms is proved to 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; mycobacteria: Mycobacterium avium complex (MAC) - the complex including: Mycobacterium avium and Micobacterium intracellulare; Helicobacter pylori. Beta лактамазы do not influence activity of a klaritromitsin.
Activity of a klaritromitsin of in vitro - aerobic gram-positive microorganisms: Listeria monocytogenes, Streptococcus agalactiae, Streptococci group of 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; mycobacteria: Mycobacterium leprae, Mycobacterium chelonae, campylobacters: Campylobacter jejuni.
Microbiological active metabolite of a klaritromitsin - 14-gidroksiklaritromitsin is twice more active, than initial connection in relation to Haemophilus influenzae. Klaritromitsin and his metabolite in a combination can render as the additive, and synergy action on Haemophilus influenzae in vitro and in vivo, depending on a strain of a bacterium.
Majority of strains of the stafilokokk steady against Methicillinum and Oxacillinum of a rezistentna against a klaritromitsin.
Development of cross resistance to a klaritromitsin and other antibiotics of group of macroleads, and also lincomycin and clindamycin is possible.

Pharmacokinetics. Absorption - bystry. Food slows down absorption, significantly without influencing bioavailability. Bioavailability of tablets of 250 mg - 50%.
Communication with proteins of plasma - 65-75%. After a single dose 2 peaks of Cmax are registered. The second peak is caused by ability of drug to collect in a gall bladder with the subsequent gradual or bystry receipt in intestines and absorption. Time of achievement of Cmax at reception of 250 mg - 2-3 h.
After intake of 20-30% of the accepted dose quickly it is hydroxylated in a liver by isoenzymes of CYP3A4, CYP3A5 and CYP3A7 cytochrome with formation of the main metabolite - a 14-gidroksiklaritromitsin having the expressed antimicrobic activity concerning Haemophilus influenzae. Is inhibitor of isoenzymes CYP3A4, CYP3A5 and CYP3A7.
At regular reception on 250 mg / Css of not changed drug and its main metabolite - 1 and 0,6 mkg/ml respectively; T1/2 - 3-4 and 5-6 h respectively. At increase in a dose up to 500 mg/days of Css of not changed drug and its metabolite in plasma - 2,7-2,9 and 0,83-0,88 mkg/ml respectively; T1/2 - 4,8-5 and 6,9-8,7 h respectively. In therapeutic concentration collects in lungs, skin and soft tissues (in them concentration by 10 times exceed antibiotic level in a blood plasma).
It is allocated with kidneys and intestines (20-30% - in not changed form, the rest - in the form of metabolites). At a single dose of 250 and 1200 mg kidneys allocate 37,9 and 46%, with intestines - 40,2 and 29,1% respectively.
At a renal failure increase in TCmax, Cmax and AUC of a klaritromitsin and its metabolite is noted.

Indications to use:

Adult:
— pharyngitis;
— tonsillitis;
— acute antritis;
— exacerbation of chronic bronchitis;
— community-acquired pneumonia;
— uncomplicated infections of skin and hypodermic cellulose;
— the disseminated infection caused by Mycobacterium avium and Mycobacterium intracellulare.

The adult in a combination with amoxicillin and omeprazolom/lansoprazoly in the form of triple therapy at the infections caused by Helicobacter pylori including a peptic ulcer of a duodenum.

To children:
— pharyngitis;
— tonsillitis;
— community-acquired pneumonia;
— acute antritis;
— acute average otitis;
— uncomplicated infections of skin and hypodermic cellulose;
— the disseminated infection caused by Mycobacterium avium and Mycobacterium intracellulare.

Route of administration and doses:

To accept inside, to swallow without chewing a tablet, washing down with a small amount of liquid.
To adults and children 12 years and with body weight more than 33 kg are more senior:
at pharyngitis and tonsillitis, the caused Streptococcus pyogenes - on 250 mg each 12 h within 10 days;
at acute antritis - on 500 mg each 12 h within 14 days;
at an exacerbation of the chronic bronchitis caused by Haemophilus influenzae - on 500 mg each 12 h within 7-14 days, the caused Haemophilus parainfluenzae - on 500 mg each 12 h within 7 days; the caused Moraxella catarrhalis, Streptococcus pneumoniae - on 250 mg each 12 h within 7-14 days;
at the community-acquired pneumonia caused by Haemophilus influenzae - on 250 mg each 12 h within 7 days, the caused Streptococcus pneumoniae, Chlamydia pneumoniae, Mycoplasma pneumoniae - no of 250 mg each 12 h within 7-14 days;
at the uncomplicated infections of skin and hypodermic cellulose caused by Staphylococcus aureus, Streptococcus pyogenes - on 250 mg each 12 h within 7-14 days.
At treatment and prevention of the infections caused by Mycobacterium avium: appoint 500 mg 2 times a day. The maximum daily dose - 1000 mg. Treatment duration - 6 months and more.
For the purpose of Helicobacter pylori eradikation:
The combined treatment by three drugs:
кларитромицин - 500 mg, лансопразол - 30 mg and amoxicillin - 1000 mg 2 times a day within 10-14 days;
кларитромицин - 500 mg, омепразол - 20 mg and amoxicillin - 1000 mg 2 times a day within 10 days.
The combined treatment by two drugs:
кларитромицин - 500 mg 3 times a day, омепразол - 40 mg a day within 14 days, with purpose of an omeprazol during the next 14 days in a dose of 20 mg a day.
For patients with a chronic renal failure (KK less than 30 ml/min. or concentration of serumal creatinine more than 3,3 mg / 100 ml) the dose is reduced twice, or increase an interval twice. The maximum duration of treatment at patients of this group - 14 days.

Features of use:

In the presence of chronic diseases of a liver it is necessary to carry out regular control of activity of enzymes in blood serum.

With care appoint against the background of the medicines which are metabolized a liver (it is recommended to measure their concentration in blood). In case of joint appointment with warfarin or other anticoagulants it is necessary to control a prothrombin time.

At development of consecutive infection adequate therapy has to be appointed.

At emergence in time or after treatment of heavy diarrhea it is necessary to exclude the diagnosis of pseudomembranous colitis which demands immediate drug withdrawal and purpose of the corresponding treatment.

Side effects:

From a nervous system: headache, dizziness, concern, sleeplessness, "dreadful" dreams, spasms, depression; disorientation, hallucinations, psychosis, depersonalization, confusion of consciousness.
From the alimentary system: nausea, vomiting, a gastralgia, diarrhea, stomatitis, a glossitis, candidiasis of a mucous membrane of an oral cavity, discoloration of language and teeth, acute pancreatitis, increase in activity of "hepatic" transaminases, hepatocellular and cholestatic hepatitis, cholestatic jaundice, it is rare - pseudomembranous colitis, pechenochnochny insufficiency with a lethal outcome generally against the background of serious associated diseases and/or the accompanying medicinal therapy.
From cardiovascular system: ventricular tachycardia, including pirouette type, trembling and ventricular fibrillation, increase in an intreval of QT at an ECG.
From sense bodys: noise, a ring in ears, taste change (dysgeusia), in isolated cases - the hearing loss passing after drug withdrawal, disturbance of sense of smell.
From a musculoskeletal system: mialgiya.
From bodies of a hemopoiesis: seldom - thrombocytopenia, (unusual bleedings, hemorrhages).
From an urinary system: intersticial nephrite.
Laboratory indicators: a leukopenia, a giperkreatininemiya, a hypoglycemia (including at a concomitant use of hypoglycemic drugs).
Allergic reactions: skin rash, itch, small tortoiseshell, dermahemia, malignant exudative erythema (Stephens-Johnson's syndrome), toxic epidermal necrolysis, anaphylactic reactions.
Others: consecutive infections (development of stability of microorganisms).

Interaction with other medicines:

At joint reception of a klaritromitsin and medicines, initially metabolized CYP3A isoenzyme, perhaps mutual increase in their concentration that can strengthen or prolong both therapeutic, and side effects.

Joint reception with astemizoly, tsizapridy, Pimozidum, terfenadiny, ergotamine and other alkaloids of an ergot is contraindicated; alprazolamy, midazolam, triazolamy.

Appoint with care with carbamazepine, tsilostazoly, cyclosporine, Disopyramidum, lovastatiny, metilpredniozolony, omeprazoly, indirect anticoagulants (including warfarin), quinidine, rifabutiny, sildenafily, simvastatiny, takrolimusy, vinblastine, and also Phenytoinum, theophylline and valproic acid (are metabolized through other isoenzymes of P450 cytochrome). Dose adjustment of medicine and control of concentration in blood is necessary.

At combined use with tsizapridy, Pimozidum, terfenadiny and astemizoly increase in concentration of the last in blood, increase in an interval of QT, emergence of arrhythmia, including ventricular tachycardia including the pirouette type and fibrillation of ventricles is possible.

At combined use with ergotamine and dihydroergotamine perhaps acute poisoning with drugs of group of ergotamine (a vascular spasm, ischemia of extremities and other fabrics, including TsNS).

Efavirenz, not Virapinum, rifampicin, рифабутин and rifapentine (P450 cytochrome inductors) reduce the level of a klaritromitsin in plasma and weaken therapeutic effect of the last, and, at the same time, increasing the level of a 14-gidroksiklaritromitsin. At joint reception of a flukonazol in a dose of 200 mg daily and a klaritromitsina in a dose of 1 g/days increase in Css and AUC of a klaritromitsin by 33% and 18%, respectively is possible. Dose adjustment of a klaritromitsin is not required.

At joint reception of a ritonavir of 600 mg/days and a klaritromitsina of 1 g/days decrease in metabolism of a klaritromitsin (increase in Cmax by 31%, Css by 182% and AUC by 77%), full suppression of formation of a 14-gidroksiklaritromitsin is possible. At patients with a chronic renal failure it is necessary for dose adjustment: at KK of 30-60 ml/min. the dose of a klaritromitsin has to be reduced by 50%, at KK less than 30 ml/min. for 75%. Ritonavir it is not necessary to accept together with klaritromitsiny in the dose exceeding 1 g/days.

At joint reception with quinidine and Disopyramidum developing of ventricular tachycardia like "pirouette" is possible. Control of an ECG (increase in an interval of QT), serumal concentration of these medicines is necessary.

Klaritromitsin increases concentration of inhibitors of GMG-KOA-reduktazy (ловастатин, симвастатин). Development of a rabdomioliz in the patients accepting these drugs jointly is possible.

At use of a klaritromitsin and omeprazol increase in Cmax, AUC and T1/2 of an omeprazol by 30%, 89% and 34% respectively is possible. Average value рН in a stomach during 24 h made 5,2 at reception only an omeprazol and 5,7 at reception of an omeprazol together with klaritromitsiny.

At use of a klaritromitsin and indirect anticoagulants strengthening of action of the last is possible.

At use of a klaritromitsin with sildenafily, tadalafily or vardenafily (phosphodiesterase-5 inhibitors), increase in the inhibiting impact on phosphodiesterase is possible. Reduction of a dose of a sildenafil, tadalafil can be required and vardenafit.

At joint use of a klaritromitsin with theophylline and carbamazepine increase in concentration of the last in a system blood-groove is possible.

At use of a klaritromitsin with tolterodiny at patients with a low metabolic rate through CYP2D6 the dose decline of a tolterodin in the presence of a klaritromitsin can be required (CYP3A inhibitor).

At joint reception of a klaritromitsin (1 g/days) with midazolam increase in AUC midazolam by 7 times is (orally) possible. It is necessary to avoid joint oral administration of a klaritromitsin and midazolam and other benzodiazepines which are metabolized by CYP3A (triazoles and alprazola). At use of midazolam (in/in) and the klaritromitsina can be required correction of a dose. The same precautionary measures should be applied also to other benzodiazepines which are metabolized by CYP3A. For benzodiazepines which removal does not depend on CYP3A (temazepam, nitrazepam, lorazepam) clinically significant interaction with klaritromitsiny is improbable.

At joint reception of a klaritromitsin with colchicine strengthening of effect of colchicine is possible. Control of possible development of clinical symptoms of intoxication by colchicine, especially at elderly patients and patients with a chronic renal failure is necessary (it was reported about cases with a lethal outcome). At joint reception of a klaritromitsin and digoxin it is necessary to control carefully concentration of digoxin in serum (possibly increase in its concentration and development of potentially lethal arrhythmias).

The concomitant use of a klaritromitsin and zidovudine adult HIV-positive patients can lead to decrease in Css of a zidovudine. Selection of doses of a klaritromitsin and zidovudine is necessary. This type of interaction does not occur at the HIV-positive children receiving кларитромицин in the form of suspension together with a zidovudine.

At joint reception of a klaritromitsin (1 g/days) and an atazanavira (400 mg/days) increase in AUC of an atazanavir by 28%, a klaritromitsina twice, reduction of AUC of a 14-gidroksiklaritromitsin by 70% is possible. At patients with KK of 30-60 ml/min. the dose of a klaritromitsin has to be reduced by 50%. Klaritromitsin in the doses exceeding 1 g/days it is impossible to appoint together with inhibitors of proteases.

At joint reception of a klaritromitsin and intrakonazol perhaps mutual increase in concentration of drugs in plasma. For the patients who are at the same time accepting итраконазол and кларитромицин careful observation because of possible strengthening or lengthening of pharmacological effects of these medicines is necessary.

At a concomitant use of a klaritromitsin (1 g/days) and a sakvinavira (in soft gelatin capsules, 1200 mg 3 times a day) increase in AUC and Css of a sakvinavir by 177% and 187% respectively, and a klaritromitsina for 40% is possible. At joint purpose of these two medicines during limited time in doses / dosage forms stated above correction of a dose is not required.

At joint reception with verapamil the lowering of arterial pressure, a bradyarrhythmia and lactic acidosis is possible.

Contraindications:

— hypersensitivity;
— porphyria;
— lactation period;
— concomitant use of a tsizaprid, astemizol, Pimozidum, terfenadin, ergotamine and other alkaloids of an ergot, peroral dosage forms of midazolam, alprazolam, triazolam;
— children's age up to 12 years (for this dosage form).
— lactose intolerance or insufficiency of lactase, and also glyukozo-galaktozny malabsorption.

With car