Klaritromitsin

General characteristics. Structure:

Active ingredient: clarithromycin;

1 tablet contains a klaritromitsin of 250 mg or 500 mg;

excipients: cellulose microcrystallic, sodium krakhmalglikolit (type A), sodium lauryl sulfate, a gipromeloz, calcium stearate, mix for a covering of "Opadry II Yellow" (contains: lactose, monohydrate).

Pharmacological properties:

Pharmacodynamics. Klaritromitsin – a semi-synthetic antibiotic of group of macroleads. Possesses bacteriostatic action of rather sensitive microorganisms. In big concentration concerning separate microorganisms can have bactericidal effect. The mechanism of antibacterial action – suppression of synthesis of protein by binding with 50S a ribosome subunit of bacteria.

Klaritromitsin is active in vitro and in clinical practice concerning the following       microorganisms:

gram-positive bacteria: Staphylococcusaureus, Streptococcuspyogenes, Streptococcuspneumoniae, Listeriamonocytogenes;

gram-negative bacteria: Haemophilusinfluenzae(parainfluenzae), Neisseriagonorrhoeae, Legionellapneumophila, Moraxellacatarrhalis;

mycobacteria:  Mycobacteriumleprae, Mycobacteriumchelonae, Mycobacteriumfortuitum, Mycobacteriumkansasii, the Mycobacteriumavium (MAC) complex which part Mycobacteriumaviumi Mycobacteriumintracellulare are;

other microorganisms: Mycoplasmapneumoniae, Chlamydiapneumonіae(TWAR).

The majority Methicillinum - and oksatsillinrezistentny strains of stafilokok are not sensitive to Klaritromitsin's action.

Klaritromitsin is active in vitrootnositelno of the majority of strains of such microorganisms, however clinical performance and safety of its use are not established:
Streptococcusagalactiae, Streptococci (C, F groups, G), Viridansgroupstreptococci, Bordetellapertussis, Pasteurellamultocida, Clostridiumperfringens, Peptococcusniger, Propionibacterium

 

acnes, Bacteriodesmelaninogenicus, Borrelia burgdorferi, Treponema pallidum, Campylobacterjejuni.

Кларитромицинпроявляетбактерицидноедействиеотносительнонесколькихштаммовбактерий: Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae, H. pylori icampylobacter spp.

Pharmacokinetics. After oral administration Klaritromitsin is quickly absorbed, reaching the maximum concentration in 2-3 hours. Keeps stability in acid medium of a stomach. Reception with food reduces speed, but not extent of absorption that Klaritromitsin irrespective of meal allows to apply.  Bioavailability – about 50%.

It is widely distributed in fabrics and liquids of an organism. Especially high concentration are reached in a mucous membrane of a nose, almonds and lungs. Having high lipophilicity and having affinity with cytoplasmic membranes, Klaritromitsin creates vysshiyekontsentration in cells and fabrics, than in a blood plasma. Collects also in high concentration in leukocytes and macrophages. Does not get through a blood-brain barrier. 80% of drug contact proteins. It is metabolized by a liver with formation of an active metabolite of a 14-gidroksiklaritromitsin which has antimicrobic activity, as well as not changed substance. It is removed with urine of 36% of a dose, with a stake of-52%.

Elimination half-life of Klaritromitsin at normal function of kidneys: at a dose of 250 mg 2 times a day –3-4 hours; at a dose of 500 mg 2 times a day – 4,5-4,8 hours. An elimination half-life of a 14-gidroksiklaritromitsin at normal function of kidneys: at a dose of 250 mg 2 times a day – 5-6chas; at a dose of 500 mg 2 times a day – 6,9-8,7 hours.

At a renal failure the size of an elimination half-life increases depending on severity of a renal failure.

Main physical and chemical properties: tablets, film coated, yellow color, with a biconvex surface, from a risky on the one hand tablet and a stamping of "KMP" with another. On cross section the kernel of white color is noticeable.

Indications to use:

The infections caused by microorganisms, sensitive to Klaritromitsin:
upper respiratory tract infections (pharyngitis, sinusitis, tonsillitis, etc.);
lower respiratory tract infections (bronchitis, pneumonia, etc.);
infections of skin and soft tissues (folliculitis, эризипелоид, etc.);
the extended or localized mikobakterialny infections;
dontogenous infections;
eradikation of Helicobacterpylori(H. pylori) at patients with a round ulcer of a duodenum at oppression of secretion of hydrochloric acid which is rendered омепразол or лансопразол (Klaritromitsin's activity against H. pylori at neutral value рН above, than at an acid rn).

Route of administration and doses:

Klaritromitsin accept orally, without chewing, washing down with a small amount of liquid, irrespective of meal.

To adults and children 12 years the recommended daily dose of Klaritromitsin are more senior makes 500 mg, divided into 2 receptions; at infections of heavy degree the daily dose can be increased to 1 g, divided into 2 receptions.

The mode of dosing and duration of a course of treatment which usually makes 5-14 days depends on type and weight of an infection, and also sensitivity of the activator.

Treatment of a mikobakterialny infection. The recommended dose for adults – 500 mg 2 times a day.

Treatment of MACK infections at patients on AIDS continues so much how many clinical and microbiological performance of drug lasts. Klaritromitsin it is necessary to apply in a complex with other antimikobakterialny means. Duration of treatment of other not tuberculosis mikobakterialny tuberculosis infections is defined the doctor individually.

Prevention of MACK infections: the recommended Klaritromitsin's dose – 500 mg 2 times a day.

Treatment of dontogenous infections: the recommended Klaritromitsin's dose – 250 mg 2 times a day within 5 days.

For an eradikation of H. pyloriу of patients with a round ulcer of a duodenum Klaritromitsin appoint as a part of complex therapy according to the approved international schemes:

1. "Triple" therapy:
within 1-2 weeks on 2 times a day: Klaritromitsin of 500 mg + amoxicillin of 1000 mg + лансопразол 30 mg;
within 1 week on 2 times a day: Klaritromitsin of 500 mg + metronidazole of 400 mg + лансопразол 30 mg;
within 1 week: Klaritromitsin of 500 mg 2 times a day + омепразол 40 mg of 1 times a day + amoxicillin of 1000 2 times a day (or metronidazole of 400 mg 2 times a day);
 within 10 days: Klaritromitsin of 500 mg 2 times a day + омепразол 20 mg of 1 times a day + amoxicillin of 1000 mg 2 times a day.

2. "Double" therapy – within 2 weeks: Klaritromitsin of 500 mg Zraza in days + омепразол 40 mg of 1 times a day.

Patients with a renal failure.

Patients with clearance of creatinine less than 30 ml/min. should reduce Klaritromitsin's dose twice – on 250 mg of 1 times a day or at heavier infections – on 250 mg 2 times a day. Treatment of such patients lasts no more than 14 days.

Patients with an abnormal liver function.

At Klaritromitsin's appointment patients with an abnormal liver function need to be careful. However at preservation of normal function of kidneys sick with a moderate or heavy abnormal liver function of dose adjustment of Klaritromitsin it is not required.

With normal function of kidneys the drug dosing does not demand correction from patients of advanced age.

Features of use:

It is necessary to pay attention to a possibility of cross resistance between Klaritromitsin and other macroleads, and also lincomycin and clindamycin.

The long or repeated course of an antibioticotherapia can lead to rapid growth of resistant microflora, development of superinfections.

It is necessary to be careful at Klaritromitsin's appointment the patient with disturbances of functions of a liver and/or kidneys, and also to patients of advanced age (see the section" Route of administration and doses").

At Klaritromitsin's reception during treatment or in 1-2 months after the termination of a course of treatment disturbances of digestive tract up to the pseudomembranous colitis caused by Clostridium difficile are possible. When developing colitis Klaritromitsin's use should be stopped and carried out the corresponding treatment.

At patients on AIDS and other patients with disturbance of immune system applying high doses of Klaritromitsin longer than it is recommended for treatment of mikobakterialny infections, it is not always possible to distinguish the side reactions and symptoms of the basic or associated diseases connected using drug.

It was reported about strengthening of symptoms of a myasthenia (myasthenia gravis) at the patients receiving Klaritromitsin.

 

Ability to influence speed of reaction at control of motor transport or work with other mechanisms. At the moment there are no messages. However at control of motor transport or work with other mechanisms it is recommended to observe extra care, considering a possibility of development of undesirable reactions from a nervous system.

Side effects:

The general hypersensitivity reactions and reactions from skin and its derivatives: urticaria, skin rash, in isolated cases – a Quincke's disease, anaphylactic reactions, Stephens-Johnson's syndrome, a Lyell's disease.

From a digestive tract and a metabolism: nausea, vomiting, an abdominal pain, abdominal distention, diarrhea, it is very rare – acute pancreatitis, a glossitis, stomatitis, dryness in a mouth, a fungal infection mucous a mouth, discoloration of language and teeth, pseudomembranous colitis.

From the central and periferichny nervous system: a headache, dizziness, feeling of alarm, it is very rare – sleeplessness, a depression, dreadful dreams, a ring in ears, a temporary hearing loss, disturbance of flavoring feelings                                         (a dysgeusia, an ageusia), disturbance of sense of smell (an anosmia, a parosmiya), paresthesias, spasms, confusion of consciousness, a disorientation, hallucinations, psychoses and depersonalization.

From cardiovascular system: ventricular tachycardia and fibrillation of ventricles, lengthening of a QT interval, ventricular tachycardia on the pirouette type.

From a liver and kidneys: increase in activity of liver enzymes, increase in indicators of creatinine in blood serum, is very rare – a liver failure, hepatitis (including cholestatic), jaundice (cholestatic, hepatocellular), intersticial nephrite, isolated cases – increase in level of urea in blood.

From system of a hemopoiesis: in isolated cases – a leukopenia, thrombocytopenia.

Others: a hypoglycemia, development of superinfection, it is very rare – a mialgiya, an arthralgia, a uveitis (it is preferential at the patients receiving the accompanying therapy rifabutiny), диспноэ. It was reported about development of kolkhitsinovy toxicity (including from the death) at the combined use of Klaritromitsin and colchicine, especially at patients of advanced age, including against the background of a renal failure.

Interaction with other medicines:

Klaritromitsin is CYP3A enzyme inhibitor therefore it is necessary to be careful at Klaritromitsin's appointment with drugs, metabolized by means of CYP3A enzyme of system of P450 cytochrome since it can lead to increase in concentration of the last in a blood plasma that, in turn, can strengthen or prolong its therapeutic effect and risk of emergence of side reactions. Treat such drugs: to alprazola, 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 and vinblastine. The similar mechanism of interaction is noted at use of Phenytoinum, theophylline and Valproatum which are metabolized by one of isoenzymes of system of P450 cytochrome.

Powerful inductors of enzymes of P450 cytochrome, such as эфавиренз, not Virapinum, rifampicin, рифабутин and rifapentine, can increase Klaritromitsin's metabolism, reducing its concentration in a blood plasma, but increasing concentration 14-ON-klaritromitsina – microbiological active metabolite. As microbiological activity of Klaritromitsin and 14-ON-klaritromitsina different in relation to various bacteria, the expected therapeutic effect can be not reached owing to the combined use of Klaritromitsin and inductors of enzymes of P450 cytochrome.

Flukonazol. Equilibrium concentration of an active metabolite 14-ON-klaritromitsina considerably did not change at simultaneous use with flukonazoly. Change of a dose of Klaritromitsin is not required.

Ritonavir. Use of a ritonavir and Klaritromitsin leads to considerable oppression of metabolism of Klaritromitsin. The maximum concentration of Klaritromitsin increases by 31%, minimum – for 182% and AUC increases by 77%. Full oppression of education 14-ON-klaritromitsina is noted. Because of the big therapeutic range of a dose decline of Klaritromitsin with normal function of kidneys it is not required from patients. At patients with a renal failure dose adjustment is necessary: at clearance of creatinine of 30-60 ml/min. Klaritromitsin's dose needs to be lowered by 50% of the maximum dose; at clearance of creatinine of ≤30 ml/min. – for 75%. Klaritromitsin's doses exceeding 1 g/days should not be applied combined with ritonaviry.

Antiarrhytmic means. At simultaneous use of Klaritromitsin with quinidine or Disopyramidum chances of a ventricular aritimiya on the pirouette type. Therefore it is necessary to carry out an ECG - monitoring and control of level of these drugs to blood during treatment by Klaritromitsin.

Simultaneous use of Klaritromitsin with terfenadiny, tsizapridy, Pimozidum or astemizoly can lead to lengthening of an interval of QT and emergence of arrhythmias, including ventricular tachycardia, fibrillation of ventricles and arrhythmia on the pirouette type. Co-administration of these drugs should be avoided.

Simultaneous use of Klaritromitsin and ergotamine or dihydroergotamine is associated with signs of an acute ergotism that it is characterized by a vasospasm and ischemia of extremities and other fabrics, including TsNS.

At a concomitant use of Klaritromitsin and inhibitors of GMG-KOA-reduktazy, for example a lovastatina or a simvastatina, it was very seldom observed рабдомиолиз.

Omeprazol. Klaritromitsin's use in a combination with omeprazoly leads to increase in equilibrium concentration of an omeprazol. At use only of an omeprazol average value рН a gastric juice at measurement during 24 h makes 5,2; at simultaneous use of an omeprazol with Klaritromitsin – 5,7.

At simultaneous use with Klaritromitsin effect of peroral anticoagulants amplifies therefore it is necessary to control the size of a prothrombin time.

Inhibitors of phosphodiesterase (FDE). There is a probability of increase in concentration in a blood plasma of FDE inhibitors (the sildenafila, tadalafit and vardenafit) at their use with Klaritromitsin that can demand a dose decline of FDE inhibitors.

Zidovudine. Simultaneous use of tablets of Klaritromitsin and a zidovudine for HIV-positive patients can cause decrease in level of a zidovudine in blood.

Digoxin. At Klaritromitsin's reception along with digoxin concentration of digoxin in blood serum can increase that demands in such cases of control of level of the last.

At simultaneous use of Klaritromitsin with rifabutiny or rifampicin Klaritromitsin's concentration in blood serum decreases (more than by 50%).

Tolterodin. The dose decline of a tolterodin can be required at its use with Klaritromitsin.

Triazolbenzodiazepines (for example to alprazola, midazolam, to triazoles). It is necessary to avoid the combined use of peroral midazolam and Klaritromitsin. For benzodiazepines which elimination does not depend on CYP3A (temazepam, nitrazepam, lorazepam) development of clinically significant interaction with Klaritromitsin is improbable. There are data on medicinal interaction and development of by-effects from TsNS (such as drowsiness and confusion of consciousness) at simultaneous use of Klaritromitsin and a triazolam. It is necessary to observe the patient, considering a possibility of strengthening of pharmacological effects from TsNS.

Colchicine. At simultaneous use of Klaritromitsin and colchicine oppression of Pgp and/or CYP3A by Klaritromitsin can lead to increase in exposure of colchicine. It is necessary to observe a condition of patients for the purpose of identification of clinical symptoms of toxicity of colchicine.

Contraindications:

Hypersensitivity to Klaritromitsin, macroleads, and also to other components of drug; simultaneous use with any of the following drugs: астемизол, цизаприд, Pimozidum, терфенадин, ergotamine or dihydroergotamine; children's age up to 12 years; feeding period breast.

Use during pregnancy or feeding by a breast. Safety of use of Klaritromitsin during pregnancy of an ilikormleniye a breast is not established. It is not necessary to use drug during pregnancy (especially in the I trimester) in the absence of vital indications to use and without careful preliminary estimate of a ratio advantage/risk. Klaritromitsin is allocated with breast milk. In need of drug use women who nurse for treatment by a breast should stop feeding.

Children. Klaritromitsin is contraindicated for use to children up to 12 years.

Overdose:

Symptoms: nausea, vomiting, diarrhea.

Treatment: immediate gastric lavage and symptomatic treatment. The hemodialysis and peritoneal dialysis do not lead to considerable change of level of Klaritromitsin in blood serum.

The patient has data on 1 case of development of changes of a mental state, paranoid behavior, a hypopotassemia and anoxemia with bipolar psychosis in the anamnesis which accepted 8 g of Klaritromitsin.

Storage conditions:

Period of storage 3 years. In original packaging at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets, film coated, in the blister, 1 blister in a pack.