Klaritromitsin

General characteristics. Structure:

Active agent: кларитромицин - 250 mg;

Excipients: cellulose of microcrystallic-33,0 mg, potato starch — 15,0 mg, povidone (polyvinylpirrolidone) - 12,0 mg, sodium carboxymethylstarch - 7,0 mg, magnesium stearate - 3,0 mg.

Excipients (cover): a gipromelloza - 5,4 mg, a macrogoal of 4000 - 1,6 mg, titanium dioxide of-3,0 mg.

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.
It is shown what кларитромицин has antibacterial effect against the following activators:
Aerobic gram-positive microorganisms: Staphylococcus aureus. Streptococcus pneumonia, Streptococcus pyogenes, Listeria monocytogenes.
Aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Branhamella (Moraxella) catarrhalis, Neiserria gonorrhoeae, Legionella pneumophila. Other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae. Mycobacteria: Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium avium complex (MAC): Mycobacterium avium, Mycobacterium intracellulare.
Products beta lactamelements do not exert impact on activity of a klaritromitsin.
The majority of strains of stafilokokk, resistant to Methicillinum and Oxacillinum have resistance and to a klaritromitsin. Kparitromitsin has effect of in vitro and concerning the majority of strains of the following microorganisms: aerobic gram-positive microorganisms of Streptococcus agalactiae, Streptococci (C,F group, G), vlridans 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 jejuni, Helicobacter pylori.

Pharmacokinetics. It is quickly soaked up from digestive tract after oral administration. Absolute bioavailability makes about 50%. At multiple dose of a dose of drug of cumulation it is not revealed, and the nature of metabolism in a human body did not change. Meal just before administration of drug increased bioavailability of drug on average by 25%. Klaritromitsin can be applied to food or during food. Communication with proteins of plasma — more than 90%. After a single dose 2 peaks of the maximum concentration are registered. The second peak is caused by ability of drug to concentrate in a gall bladder with the subsequent gradual or bystry receipt in intestines and absorption. Time of achievement of the maximum concentration at oral administration of 250 mg — 1-3 hours. After intake of 20% of the accepted dose quickly it is hydroxylated in a liver by enzymes of CYP3A4, CYP3A5, CYP3A7 cytochrome with formation of the main metabolite — a 14-gidroksiklaritromitsin having the expressed antimicrobic activity concerning Haemophilus influenzae. At regular reception on 250 mg/days concentration of not changed drug and its main metabolite — 1 and 0,6 mkg/ml respectively; an elimination half-life — 3-4 and 5-6 hours 4,8-5 and 6,9-8,7 hours respectively. In therapeutic concentration collects in lungs, skin and soft tissues (in them concentration by 10 times exceed level in blood serum).
It is allocated with kidneys and through the digestive tract (DT) (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%, through a GIT — 40,2 and 29,1% respectively.

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to drug;
Infections of upper parts of respiratory tracts; infections of LOR-bodies (pharyngitis, sinusitis);
Infections of lower parts of respiratory tracts (pneumonia, bronchitis);
Infections of skin and soft tissues (folliculitis, phlegmon, ugly face);
Dontogenous infections;
The Mikobakterialny infections caused by Mycobacterium avium, Mycobacterium intracellular the localized infections, caused by Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum.
Prevention of spread of the infection caused by the Mycobacterium avium (MAC) complex, the HIV-positive patient with the maintenance of lymphocytes of CD 4 (T-helper lymphocytes) of no more than 100 in 1 mm3.
For an eradikation of Helicobacter pylori and decrease in frequency of a recurrence of a peptic ulcer of a duodenum.

Route of administration and doses:

Inside regardless of meal.
Adults and children are more senior than 12 years (at body weight more than 40 kg): the standard dose makes 250 mg of 2 times a day, with an interval of 12 hours. At the sinusitis, heavy infections including caused by Haemophilus influenzae a dose about 500 mg 2 times a day, with an interval of 12 hours can be increased.
The average duration of a course of treatment makes 7-14 days.
For patients with a liver failure the recommended dose - to 250 mg is each 24 hours.
For patients with a renal failure (clearance of creatinine less than 30 ml/min.) the recommended dose makes 250 mg each 24 hours or, at heavier infections - on 250 mg 2 times a day, with an interval of 12 hours.
At mikobakterialny infections appoint 500 mg of drug 2 times a day, with an interval of 12 hours.
At the widespread infections caused by MAC at patients with AIDS:
The recommended dose of a klaritromitsin for adults and children is more senior than 12 years (at body weight more than 40 kg) - 500 mg 2 times a day, with an interval of 12 hours.
Treatment should be continued until there are clinical and microbiological confirmations of its advantage. Klaritromitsin it is necessary to appoint in a combination with other germicides.
For prevention of the infections caused by MAC:
The recommended dose of a klaritromitsin for adults and children is more senior than 12 years (at body weight more than 40 kg) - 500 mg 2 times a day, with an interval of 12 hours.
At dontogenous infections the dose of a klaritromitsin makes 250 mg 2 times a day within 5 days.
For N.'s eradikation of pylori
The combined treatment by three drugs:
Klaritromitsin, po.500 mg 2 times a day, in a combination with lansoprazoly, on 30 mg 2 times a day, and amoxicillin, on 1000 mg 2 times a day, a current of 10 days.
Klaritromitsin, on 500 mg 2 times a day, in a combination with amoxicillin, on 1000 mg 2 times a day, and omeprazoly, on 20 mg/days, within 7-10 days.
The combined treatment by two drugs
Klaritromitsin, on 500 mg 3 times a day, in a combination with omeprazoly in a dose of 40 mg/days, within 14 days, with appointment during the next 14 days of an omeprazol in a dose of 20-40 mg/days.
Klaritromitsin, on 500 mg 3 times a day, in a combination with lansoprazoly in a dose of 60 mg/days, within 14 days. For full healing of an ulcer additional decrease in acidity of a gastric juice can be required.

Features of use:

In the presence of chronic diseases of a liver it is necessary to carry out regular control of "hepatic" enzymes to blood sera.
In case of joint appointment with warfarin or other indirect anticoagulants, it is necessary to control a prothrombin time.

Side effects:

- From the alimentary system: loss of appetite, nausea, vomiting, diarrhea, abdominal pains, stomatitises, glossites, pancreatitis, discoloration of language and teeth; extremely seldom — a pseudomembranous coloenteritis. Discoloration of teeth is reversibly and usually recovered by special processing in dental clinic. As well as at reception of other antibiotics from group of macroleads abnormal liver functions, including increase in activity of liver enzymes, pechenochnokletochny and/or cholestatic hepatitis with jaundice or without it are possible. These abnormal liver functions can be heavy, but is usual they are reversible. Cases of a liver failure and death generally against the background of serious associated diseases and/or the accompanying medicinal therapy were very seldom observed.
- From a nervous system: dizziness, a headache, paresthesia, disorders of sense of smell, change of flavoring feelings, excitement, sleeplessness, dreadful dreams, sensation of fear, a ring in ears; seldom — a disorientation, hallucinations, psychosis, depersonalization, confusion of consciousness.
- From cardiovascular system: as well as at reception of other macroleads lengthening of an interval of QT, ventricular tachycardia; polymorphic ventricular tachyarrhythmia (torsade de pointe).
- From bodies of a hemopoiesis and system of a hemostasis: seldom — a leukopenia and thrombocytopenia (unusual bleedings, hemorrhages). From a musculoskeletal system: arthralgia, mialgiya.
- From an urinary system: separate cases of increase in creatinine of a blood plasma, intersticial nephrite, renal failure.
- Allergic reactions: dermahemia, urticaria, skin rash, angaonevrotichesky hypostasis, бронхоспаэм, eosinophilia; seldom — an acute anaphylaxis, Stephens-Johnson's syndrome.
- Other: fervescence, is possible development of superinfection, candidiasis, development of stability of microorganisms.

Interaction with other medicines:

Klaritromitsin do not appoint along with tsizapridy, Pimozidum, terfenadiny.
The concomitant use of a klaritromitsin with the drugs which are metabolized with the participation of P450 cytochrome can lead to increase in concentration of such drugs in a blood plasma as: to triazoles, астемизол, carbamazepine, цилостазол, цизаприд, cyclosporine, Disopyramidum, ergot alkaloids, ловастатин, Methylprednisolonum, midazolam, омепразол, peroral anticoagulants (for example warfarin), Pimozidum, quinidine, рифабутин, sildenafit, симвастатин, такролимус, терфенадин, to triazoles, vinblastine, Phenytoinum, theophylline and valproic acid.
At simultaneous use of a klaritromitsin with tsizapridy increase in concentration of a tsizaprid was observed. It can cause increase in an interval of QT, arrhythmia, ventricular tachycardia, fibrillation and a torsade de pointes of ventricles. Similar effects were observed at the patients accepting кларитромицин along with Pimozidum.
Drugs of group of macroleads influence metabolism of a terfenadin. Level of a terfenadin in blood increases that can be followed by development of arrhythmia, increase in an interval of QT, ventricular tachycardia, fibrillation and a torsade de pointes of ventricles. The maintenance of acid metabolites of a terfenadin increases by 2-3 times, the interval of QT increases, however, it does not cause any clinical manifestations. The same picture was observed at a concomitant use of an astemizol with drugs of group of macroleads.
There are messages on development of a torsade de pointes of ventricles at simultaneous use of a klaritromitsin and quinidine, and Disopyramidum. At co-administration of the specified drugs monitoring of their concentration in blood is required. At simultaneous use of a klaritromitsin with digoxin increase in content of digoxin in serum was observed. At such patients it is necessary to watch the content of digoxin in serum.
At simultaneous use of theophylline and carbamazepine with klaritromitsiny it is noted moderate, but reliable (р <0.05) increase in content of theophylline and carbamazepine in a blood plasma.
At a concomitant use of a klaritromitsin with inhibitors gidroksimetilglutaril-KOA (GMG-KOA) reductases (for example ловастатин and симвастатин) are described exceptional cases of a rabdomioliz.
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, 3 glycoproteins and/or CYP3A can lead inhibition to strengthening of effect of colchicine. Patients should be observed carefully for the purpose of identification of symptoms of toxic effect of colchicine.
At concomitant oral administration of a klaritromitsin and zidovudine at HIV-positive patients decrease in equilibrium concentration of a zidovudine was observed. As кларитромицин influences absorption of a zidovudine, reception of these two drugs should be divided in time.
Ritonavir significantly slows down metabolism of a klaritromitsin at a concomitant use. At the same time Cmax value of a klaritromitsin increases by 31%, the minimum concentration (Cmin) - for 182%, the area under a curve "concentration time" - for 77%. Essential delay of process of formation of a 14-gidroksiklaritromitsin is observed. In this case patients without renal failure have no need to adjust a dose of a klaritromitsin. At reception of a ritonavir it is not necessary to appoint at the same time a dosage of a klaritromitsin more than 1 g a day.
Development of cross resistance between klaritromitsiny and other drugs of group of macroleads, such as lincomycin and clindamycin is possible. At simultaneous use of a klaritromitsin and hypoglycemic means, including insulin, development of a hypoglycemia is in rare instances possible.

Contraindications:

- Hypersensitivity to a klaritromitsin or other components of drug;
- First trimester of pregnancy;
- Lactation period;
- Porphyria;
- A concomitant use of a klaritromitsin with the following drugs: астемизол, цизаприд, Pimozidum, терфенадин, ergotamine, dihydroergotamine (see Interaction with other medicines);
- Children's age up to 12 years or at body weight less than 40 kg (for this dosage form).

With care appoint to patients with abnormal liver functions and kidneys.

Pregnancy and period of a lactation
Klaritromitsin is contraindicated in the first trimester of pregnancy. In the second and third trimesters of pregnancy drug is appointed only in the presence of accurate indications if the estimated advantage for mother exceeds potential risk for a fruit. In need of appointment in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Overdose:

Symptoms: symptoms from digestive tract; at one patient with bipolar disorder in the anamnesis after reception of 8 g of a klaritromitsin disturbances of a mental state, paranoid behavior, a hypoglycemia, an anoxemia are described.

Treatment: gastric lavage, symptomatic therapy.
The specific antidote does not exist.

Storage conditions:

List B.
To store in the dry, protected from light place at a temperature not above 25 °C.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated 250 mg.
On 10 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 10, 20, 30, 40, 50 or 100 tablets in a container polymeric for medicines. One container or 1, 2, 3, 4, 5, 6, 8 or 10 blister strip packagings together with the application instruction place in a pack from a cardboard.