Клацид®

General characteristics. Structure:

Klatsid, powder for preparation of suspension for intake of 125 mg / 5 ml

Active agent: кларитромицин 125 mg / 5 ml.

Excipients (contents in mg / 5 ml): carbomer (карбопол 974P) 75,0; K90 17,5 povidone; gipromeloza phthalate 152,1; castor oil 16,1; silicon dioxide 5,0; maltodextrin 285,7; sucrose 2748,3; titanium dioxide 35,7; xanthane gum 3,8; fragrance fruit 35,7; potassium sorbate 20,0; citric acid anhydrous 4,2.

Klatsid, powder for preparation of suspension for intake of 250 mg / 5 ml

Active agent: кларитромицин 250 mg / 5 ml.

Excipients (contents in mg / 5 ml): carbomer (карбопол 974P) 150,0; K90 35,0 povidone; gipromeloza phthalate 304,2; castor oil 32,1; silicon dioxide 1000,0; maltodextrin 238,1; sucrose 2418,89; titanium dioxide 35,7; xanthane pitch 3,8; fruit fragrance 35,7; potassium sorbate 20,0; citric acid anhydrous 4,24.

DESCRIPTION

Klatsid, powder for preparation of suspension for reception vnutr125 mg / 5мл

The white or almost white granulated powder with fruit aroma. When stirring with water white or almost white opaque suspension with fruit aroma.

Klatsid, powder for preparation of suspension for intake of 250 mg / 5мл

The granules of white or almost white color having fruit aroma. At addition of water the white or almost white opaque suspension having fruit aroma is formed.

Pharmacological properties:

Pharmacodynamics. Klaritromitsin is a semi-synthetic antibiotic of group of macroleads and has antibacterial effect, interacting with 50S a ribosome subunit of sensitive bacteria and suppressing protein synthesis.

Klaritromitsin showed high activity of in vitro against the standard and polished cultures of bacteria. It is highly effective concerning many aerobic and anaerobic gram-positive and gram-negative microorganisms. Klaritromitsin is highly effective in vitro concerning Legionella pneumophila, Mycoplasma pneumoniae and Helicobacter (Campylobacter) pylori.

Enterobacteriaceae and Pseudomonas also as well as others, the gram-negative bacteria which are not decomposing lactose are not sensitive to a klaritromitsin.

It is shown what кларитромицин has antibacterial effect against the following activators:

Aerobic gram-positive microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes.

Aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Legionella pneumophila. Other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae (TWAR), Chlamydia trachomatis. Mycobacteria: Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium avium complex (MAC): Mycobacterium avium, Mycobacterium Intracellulare.

Klaritromitsin has effect of in vitro and concerning the majority of strains of the following microorganisms (however safety and efficiency of use of a klaritromitsin in clinical practice is not confirmed with clinical trials and practical value remains not clear): aerobic gram-positive microorganisms — Streptococcus agalactiae, Streptococci (the C,F groups, G), Viridans group streptococci; aerobic gram-negative microorganisms — Bordetella pertussis, Pasteurella multocida; anaerobic gram-positive microorganisms of Clostridium perfringens, Peptococcus niger, Propionibacterium acnes; anaerobic gram-negative microorganisms — Bacteroides melaninogenicus; spirochetes — Borrelia burgdorferi, Treponema pallidum; Campylobacter — Campylobacter jejuni.

The main metabolite of a klaritromitsin in a human body is microbiological active metabolite 14-gidroksiklaritromitsin (14-OH-кларитромицин). Microbiological activity of a metabolite same as at initial substance, or is 1-2 times weaker concerning the majority of microorganisms. The exception makes H.influenzae concerning which efficiency of a metabolite is twice higher. Initial substance and its main metabolite render either the additive, or synergy effect concerning H.influenzae in the conditions of in vitro and in vivo depending on culture of bacteria.

Pharmacokinetics. The first data on pharmacokinetics were obtained when studying tablets of a klaritromitsin. Drug is quickly soaked up in digestive tract. Absolute bioavailability of tablets of a klaritromitsin on 50 mg makes about 50%. Food detained the beginning of absorption and formation of an active metabolite 14-ON-klaritromitsina a little, however did not influence bioavailability of drug.

In vitro

In the researches in vitro linkng of a klaritromitsin with proteins of plasma averaged about 70% at clinically significant concentration from 0,45 to 4,5 mkg/ml.

Healthy

Bioavailability and pharmacokinetics of suspension of a klaritromitsin were studied at healthy adults and children. At a single dose adults had an equivalent bioavailability of suspension that for tablets (in both cases the dose made 250 mg) or exceeded it a little. As well as in case of tablets, food detained absorption of suspension of a klaritromitsin a little, but did not influence the general bioavailability of drug. Cmax, AUC and T1/2 of a klaritromitsin at reception of children's suspension (after food) made 0,95 mkg/ml, 6,5 ¼¬ú.þ/ml and 3,7 hours respectively, and at reception of a tablet of 250 mg on an empty stomach - 1,10 mkg/ml, 6,3 ¼¬ú.þ/ml and 3,3 hours.

At use of suspension of a klaritromitsin in a dose of 250 mg each 12 hours at adults equilibrium levels in blood were practically reached to reception of the fifth dose. At the same time parameters of pharmacokinetics were the following: Cmax of 1,98 mkg/ml, AUC 11,5 ¼¬ú.þ/ml, to Tmax is 2,8 hours and T1/2 3,2 hours for a klaritromitsin and respectively 0.67, 5.33, 2.9 and 4.9 for 14-ON-klaritromitsina.

At healthy people serumal concentration reached peak within 2 hours after intake. The maximum equilibrium concentration of the main metabolite — 14-ON-klaritromitsina makes about 0,6 mkg/ml, and the elimination half-life at use of drug is equal each 12 hours in a dose of 250 mg 5-6 hours. At purpose of a klaritromitsin in a dose of 500 mg each 12 hours the maximum equilibrium concentration 14-ON-klaritromitsina is slightly higher (to 1 mkg/ml), and the elimination half-life makes about 7 hours. At use of both doses equilibrium concentration of a metabolite are usually reached within 2-3 days.

At purpose of a klaritromitsin in a dose of 250 mg each 12 hours about 20% of a dose it is removed by kidneys in not changed look. At its use in a dose of 500 mg each 12 hours kidneys in not changed look remove about 30% of a dose. The renal clearance of a klaritromitsin significantly does not depend on a dose and approaches a normal glomerular filtration rate. The main metabolite found in urine is 14-ON-klaritromitsin which share makes 10-15% of a dose (250 or 500 mg each 12 hours).

Patients

Klaritromitsin and his 14-IT-metabolite are well distributed in fabric and liquid of an organism. Fabric concentration usually are several times higher than serumal. In the table examples of fabric and serumal concentration are given:

Concentration (to 250 mg there are each 12 hours)

Fabrics                          Fabric (mkg/g)    Serumal (mkg/ml)  
Almonds Easy                                       1,6 0,8
                                                                       8,8 1,7

At the children needing peroral treatment by antibiotics кларитромицин it is characterized by high bioavailability. At the same time the adults accepting the same suspension had a similar profile of its pharmacokinetics to those. Drug is quickly and well soaked up at children. Food detains absorption of a klaritromitsin a little, however has no significant effect on its bioavailability or pharmacokinetic properties. The equilibrium parameters of pharmacokinetics of a klaritromitsin reached in 5 days (the ninth dose) were the following: Cmax of 4,60 mkg/ml, AUC 15,7 ¼¬ú.þ/ml and Tmax of 2,8 h; the corresponding values for 14-OH metabolites equaled 1,64 mkg/ml, 6,69 ¼¬ú.þ/ml and 2,7 hours respectively.

Settlement elimination half-lives of a klaritromitsin and its metabolite equal 2,2 and 4,3 hours respectively.

At patients with otitis in 2,5 hours after reception of the fifth dose (7,5 mg/kg two times a day) average concentration of a klaritromitsin and 14-IT-metabolite to fish soup averaged 2,53 and 1,27 mkg/g. Concentration of drug and its metabolite surpassed their serumal levels twice.

Abnormal liver function

Equilibrium concentration of a klaritromitsin at patients with the broken function of a liver do not differ from those at healthy people while levels 14-ON-klaritromitsina were lower. Decrease in education 14-ON-klaritromitsina at patients with the broken function of a liver at least partially was leveled by increase in renal clearance of a klaritromitsin in comparison with that at healthy people.

Renal failure

The pharmacokinetics of a klaritromitsin changed also at patients with a renal failure who received drug inside in a dose of 500 mg repeatedly. Such patients have levels in plasma, the elimination half-life, Cmax, Cmin and AUC of a klaritromitsin and it 14-ON-mettabolita were higher, than at healthy people. Deviations of these parameters correlated with degree a renal failure: at more expressed renal failure of distinction were more considerable. (see the Route of administration and doses).

Elderly people

In a comparative research at the elderly healthy people receiving кларитромицин repeatedly inside in a dose of 500 mg revealed increase in levels of drug in plasma and delay of removal in comparison with those at young healthy people. However differences between two groups did not reveal when the amendment on clearance of creatinine was made. The conclusion was drawn that changes of pharmacokinetics of a klaritromitsin reflect function of kidneys, but not age of the patient.

Patients with mikobakterialny infections

And 14-ON-klaritromitsina the patients with HIV infection receiving кларитромицин in usual doses (tablets at adults, suspension at children), had similar equilibrium concentration of a klaritromitsin to those at healthy people. However at use of a klaritromitsin in higher doses which can be required for treatment of mikobakterialny infections concentration of an antibiotic can exceed usual considerably.

At the children with HIV infection accepting кларитромицин in a dose of 15-30 mg/kg/days in two steps equilibrium Cmax values usually made from 8 to 20 mkg/ml. However at the children with HIV infection receiving suspension of a klaritromitsin in a dose of 30 mg/kg/days in two steps Cmax reached 23 mkg/ml. At use of drug in higher doses lengthening of an elimination half-life in comparison with that at the healthy people receiving кларитромицин in usual doses was noted. Increase in concentration in plasma and duration of an elimination half-life at purpose of a klaritromitsin in higher doses will be coordinated with the known nonlinearity of pharmacokinetics of drug.

Indications to use:

infections of a lower part of respiratory tracts (such as bronchitis, pneumonia).
infections of an upper part of respiratory tracts (such as pharyngitis, sinusitis), otitises.
infections of skin and soft tissues (such as folliculitis, erysipelatous inflammation).

The extended or localized mikobakterialny infections caused by Mycobacterium avium and Mycobacterium intracellulare. The localized infections caused by Mycobacterium chelonae, Mycobacterium fortuitum and Mycobacterium kansasii. Klaritromitsin is shown for N.'s elimination pylori and decrease in frequency of a recurrence of an ulcer of a duodenum.

Route of administration and doses:

For intake. Ready suspension can be accepted with food or without, including with milk. Preparation of KLATsIDA for use: with granules gradually add water to a tag to a bottle. Then a bottle stir up for receiving 60 ml of the suspension containing in 5 ml — 125 mg of a klaritromitsin or for receiving 100 ml of the suspension containing in 5 ml — 250 mg of a klaritromitsin.

Before each use it is good to stir up a bottle with drug. Ready suspension can be stored within 14 days at the room temperature.

The recommended daily dose of suspension of a klaritromitsin at nemikobakterialny infections at children makes 7,5 mg/kg two times a day (maximum — 500 mg two times a day). The usual duration of treatment — 5-7 days depending on the activator and weight of a state.

Recommendations about dosing are provided in the table:

The recommended doses at children taking into account body weight

Body weight *            Doses are specified in standard teaspoons
                                (5 ml) twice a day
Kg                            of 125 mg / 5 ml                          of 250 mg / 5 ml
                                8-11 0,5                                        -
                                                                       12-19 1 0,5
                             20-29 1,5                                       0,75
                                30-40 2                                          1

* At children with body weight <8 kg select a dose for weight (about 7,5 mg/kg twice a day)

Dosage at patients with a renal failure

At children with clearance of creatinine less than 30 ml/min. a dose of a klaritromitsin should be lowered twice, i.e. to 250 mg once a day or 250 mg twice a day at heavier infections. In such cases the course of treatment should not exceed 14 days.

Dosage at patients with mikobakterialny infections

At children with the disseminated or local mikobakterialny infections (M. of avium, M. intracellulare, M. chelonae, M. fortuitum, M. kansasii) the recommended dose of a klaritromitsin makes 15-30 mg/kg/days in two steps.

Treatment klaritromitsiny should be continued until the clinical effect remains. There can be useful an accession of other antimikobakterialny drugs.

The recommended Klatsid's doses of 250 mg / 5 ml at children with AIDS taking into account body weight

Body weight *     Doses are specified in standard teaspoons (5 ml)
Kg                            of 15                        mg/kg 30 mg/kg
                            8-11 0,5                                     1
12-19

                           20-29 1                                       2                  
30-40
                                                                       1,5 3
                                                                          2 4

* At children with body weight <8 kg select a dose for weight

(15-30 mg/kg/days)

Features of use:

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

With care appoint against the background of the drugs which are metabolized a liver (see Interaction with other medicines).

In case of joint appointment with warfarin or other indirect anticoagulants, it is necessary to control a prothrombin time.

Side effects:

KLATsID suspension on safety is comparable to tablets of 250 mg at adults. Most often the undesirable phenomena from digestive tract met, including diarrhea, vomiting, an abdominal pain and nausea. The pseudomembranous coloenteritis was extremely seldom observed. Other undesirable reactions included a headache, disturbance of taste and passing increase in activity of liver enzymes. As well as at use of other antibiotics of group of macroleads development of stability of microorganisms can be noted.

Post-marketing experience

At treatment klaritromitsiny, as well as other macroleads, infrequently noted abnormal liver functions, including increase in activity of liver enzymes, and the hepatocellular and/or cholestatic hepatitis which was followed or not being followed by jaundice. Hepatic dysfunction can be heavy and usually reversible. Seldom or never registered death cases from a liver failure which were usually observed in the presence of serious associated diseases and/or simultaneous use of other medicines.

Separate cases of increase in serumal level of creatinine are described, however their connection with drug is not established.

At oral administration of a klaritromitsin allergic reactions which varied from a small tortoiseshell and small rashes to an anaphylaxis and Stephens Johnson's syndrome / a toxic epidermal necrolysis are described. There are messages on passing effects on the central nervous system, including dizziness, alarm, sleeplessness, dreadful dreams, a sonitus, confusion of consciousness, a disorientation, hallucinations, psychosis and depersonalization; their cause and effect connection with drug is not established.

At treatment klaritromitsiny hearing loss cases are described; after the treatment termination hearing was usually recovered. Cases of disturbances of sense of smell which were usually combined with a food faddism are also known.

At treatment klaritromitsiny the glossitis, stomatitis, the milkwoman of an oral cavity and discoloration of language are described. Cases of discoloration of teeth at the patients receiving кларитромицин are known. These changes usually reversible can be also eliminated by the stomatologist.

Exceptional cases of a hypoglycemia some of which were noted at the patients receiving peroral antihyperglycemic means or insulin are described.

Separate cases of a leukopenia and thrombocytopenia are registered.

At treatment klaritromitsiny, as well as other macroleads, in rare instances noted lengthening of an interval of QT, ventricular tachycardia and ventricular tachycardia on the pirouette type.

Exceptional cases of pancreatitis and spasms are described.

There are messages on development of intersticial nephrite at treatment klaritromitsiny.

In clinical practice cases of toxicity of colchicine at its combination are described with klaritromitsiny, especially at elderly people. Some of them were observed at patients with a renal failure; it was reported about several cases of death at similar patients (See Interaction with other drugs: Colchicine).

Children with the suppressed immunity

At the patients with AIDS and other immunodeficiencies receiving кларитромицин in higher doses for a long time for treatment of mikobakterialny infections it is often difficult to differentiate undesirable effects of drug of symptoms of HIV infection or intercurrent diseases.

At limited number of children with AIDS children's suspension of a klaritromitsin was applied to treatment of mikobakterialny infections. The sonitus, deafness, vomiting, nausea, an abdominal pain, a purpura, pancreatitis and increase in activity of amylase were the main undesirable phenomena which are not connected with a basic disease. In this research registered considerable deviations of laboratory indicators from normative values (sharp increase or decrease). On the basis of these criteria at one child with AIDS receiving кларитромицин in a dose <15 mg/kg/days, substantial increase of level of the general bilirubin is noted; among the patients accepting кларитромицин in a dose of 15-25 mg/kg/days about one case of substantial increase of the ALT levels, residual nitrogen of urea and decrease in number of thrombocytes was registered. At the patients receiving кларитромицин in the maximum dose (> 25 mg/kg/days) considerable changes of the specified laboratory parameters were not revealed.

Interaction with other medicines:

Klaritromitsin is metabolized in a liver under the influence of an isoenzyme of P450 3A cytochrome (CYP3A). This mechanism defines many interactions with other drugs. Klaritromitsin can inhibit biotransformation of other medicinal substances under the influence of this system that can lead to increase in their serumal levels.

It is known or is supposed that the following medicines are metabolized under the influence of the same isoenzyme of CYP3A: to alprazola, астемизол, carbamazepine, цилостазол, цизаприд, cyclosporine, Disopyramidum, ergotamine alkaloids, ловастатин, Methylprednisolonum, midazolam, омепразол, peroral anticoagulants (for example, warfarin), Pimozidum, quinidine, рифабутин, sildenafit, симвастатин, такролимус, терфенадин, to triazoles and vinblastine.

Similar mechanisms of interaction which are mediated by other isoenzymes of P450 cytochrome are characteristic of Phenytoinum, theophylline and valproic acid.

In clinical trials at a combination of theophylline or a kabramazepin with klaritromitsiny it was noted small, but statistically significant (р <0,05) increase in levels of theophylline and carbamazepine in blood serum.

In clinical practice at use of drugs of erythromycin and/or a klaritromitsin the following cases of interaction mediated by CYP3A were registered:

At the combined use of a klaritromitsin with HMG-CoA reductase inhibitors, such as ловастатин and симвастатин, in rare instances developed рабдомиолиз.

At simultaneous use of a klaritromitsin with tsizapridy increase in levels of the last was observed. It can lead to lengthening of an interval of QT and development of cardiac arrhythmias, including ventricular tachycardia, fibrillation of ventricles and polymorphic ventricular tachycardia on the pirouette type. Similar effects were registered at the patients receiving кларитромицин with Pimozidum (see Contraindications).

Macroleads caused disturbance of metabolism of a terfenadin that led to increase in its levels in plasma and sometimes was associated with development of arrhythmias, including lengthenings of an interval of QT, ventricular tachycardia, fibrillation of zheludochkov and ventricular tachycardia on the pirouette type (see Contraindications). In one research at 14 healthy volunteers the combined use of tablets of a klaritromitsin and terfenadin led to increase in serumal level of an acid metabolite of a terfenadin by 2-3 times and to lengthening of an interval of QT which was not followed by any clinical effects.

In clinical practice cases of ventricular tachycardia on the pirouette type at a combination of a klaritromitsin to quinidine or Disopyramidum are registered. At treatment klaritromitsiny it is necessary to control serumal levels of these drugs.

Ergotamine / дигидроэрготамин:

In clinical practice at a combination of a klaritromitsin to ergotamine or dihydroergotamine registered cases of acute toxicity of the last which is characterized by a vasospasm and ischemia of extremities and other fabrics, including the central nervous system.

Interaction with other drugs

At the patients receiving кларитромицин in tablets in combination with digoxin observed increase in serumal concentration of the last. Monitoring of serumal levels of digoxin is reasonable. Development of cross resistance between klaritromitsiny, lincomycin and clindamycin is possible.

Colchicine: colchicine is substrate for CYP3A and the R-glycoprotein. Klaritromitsin and other macroleads are CYP3A inhibitors and the R-glycoprotein. At joint purpose of colchicine and a klaritromitsin, the inhibition of the R-glycoprotein and/or CYP3A can lead to strengthening of effect of colchicine. Patients should be observed carefully for the purpose of identification of symptoms of toxic effect of colchicine. Interaction with anti-retrovirus means

Simultaneous oral administration of a klaritromitsin in tablets with a zidovudine at HIV-positive adult patients can lead to decrease in equilibrium concentration of a zidovudine. Similar interaction was not observed at the HIV-positive children accepting children's suspension of a klaritromitsin with a zidovudine or didezoksiinoziny.

In a pharmacokinetic research the combined use of a ritonavir in a dose of 200 mg each 8 hours and a klaritromitsin in a dose of 500 mg each 12 hours led to considerable suppression of metabolism of a klaritromitsin. Cmax of a klaritromitsin at a combination with ritonaviry increased by 31%, Cmin — for 182%, AUC — for 77%. Actually complete inhibition of education 14-ON-klaritromitsina was noted. Considering a high therapeutic index of a klaritromitsin, decrease in its dose is not required from patients with normal function of kidneys. However at patients with a renal failure dose adjustment is reasonable. At patients with clearance of creatinine of 30-60 ml/min. the dose of a klaritromitsin is lowered by 50%, and at patients with clearance of creatinine <30 ml/min. — for 75%. In doses more than 1 g/days кларитромицин should not be applied in combination with ritonaviry.

Contraindications:

hypersensitivity to drugs of group of macroleads;
heavy abnormal liver functions and/or kidneys (clearance of creatinine less than 30 ml/min.);
concomitant use of a klaritromitsin with the following drugs: астемизол, цизаприд, Pimozidum and терфенадин, ergotamine, dihydroergotamine (see Interaction with other medicines);
porphyria;
pregnancy;
lactation period.

With care

disturbances of functions of a liver and kidneys.

Use during pregnancy and at a lactation

Safety of use of a klaritromitsin for pregnant women and the feeding women is not studied. It is known what кларитромицин is removed with breast milk. Therefore, it is recommended to apply кларитромицин during pregnancy and in the period of a lactation only when there is no safer alternative, and the risk connected with a disease exceeds possible harm for mother and a fruit.

Overdose:

At overdose it is necessary to remove not absorbed drug from digestive tract and to carry out a gastric lavage and symptomatic therapy. The hemodialysis and peritoneal dialysis has no significant effect on the level of a klaritromitsin in serum that is characteristic also of other drugs of group of macroleads.

Storage conditions:

List B. To store in the place protected from light at a temperature not above 30 °C. To store in the place, unavailable to children. PERIOD OF VALIDITY 2 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Powder for preparation of suspension for intake of 125 mg / 5мл: 42,3 g of drug in the plastic bottle which is closed a polypropylene cap. On a bottle the tag in the form of the line is put. 1 bottle of 60 ml complete with a dosing spoon or the dosing syringe in cardboard packs together with the application instruction.

Powder for preparation of suspension for intake of 250 mg / 5мл: 70,7 g of drug in the plastic bottle which is closed a polypropylene cap. On a bottle the tag in the form of the line is put. 1 bottle of 100 ml complete with a dosing spoon or the dosing syringe in cardboard packs together with the application instruction.