Claritrosin - instructions for use, dose, side effects, contraindications

Excipients: composition of the core: microcrystalline cellulose to the core weight of 0.5 g / 1.0 g, povidone (polyvinylpyrrolidone) 21 mg / 42 mg, sodium carboxymethyl starch (sodium starch glycolate) 40 mg / 80 mg, lactose monohydrate (milk sugar) 20 mg / 40 mg, potato starch 60.5 mg / 121 mg, silicon dioxide colloid (aerosil) 5 mg / 10 mg, magnesium stearate 5 mg / 10 mg, talc 15 mg / 30 mg;

shell composition: hypromellose (hydroxypropylmethylcellulose) 10.53 mg / 21.06 mg, titanium dioxide (titanium dioxide) 3.85 mg / 7.7 mg, macrogol-4000 10.52 mg / 21.04 mg, tropelin-O 0 dye, 1 mg / 0.2 mg.

Description:

Tablets with a dosage of 250 mg: round biconvex form, covered with a film coating of yellow color.

Tablets with a dosage of 500 mg: oval, covered with a film shell of yellow color. On the cross-section, one layer of white or almost white color is visible.

Pharmacotherapeutic group:antibiotic-macrolide

ATX: & nbsp

J.01.F.A.09 Clarithromycin

Pharmacodynamics:

Clarithromycin is a semisynthetic antibiotic of the macrolide group and has an antibacterial effect, interacting with 50S ribosomal subunit of sensitive bacteria and suppressing protein synthesis.

Tablets of prolonged action are a homogeneous crystalline base, when passing through the gastrointestinal tract, a sustained release of the active substance is provided.

Clarithromycin showed high activity in vitro against standard and isolated cultures of bacteria. It is highly effective against many aerobic and anaerobic gram-positive and gram-negative microorganisms. Clarithromycin in vitro is highly effective in relation to Legionella pneumophila and Mycoplasma pneumoniae.

Enterobacteriaceae and Pseudomonas as well as other non-lactose-degrading gram-negative bacteria are not sensitive to clarithromycin.

Shown, that clarithromycin has antibacterial action against the following pathogens:

- aerobic Gram-positive microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus viridans, Listeria monocytogenes;

- aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Legionella pneumophila, Pasteurella multocida, Helicobacter pylori, Campylobacter jejuni, Moraxella (Branhamella) catarrhalis;

- other microorganisms: Mycoplasma pneumonia, Chlamydophila pneumoniae (TWAR), Chlamydia trachomatis, Borrelia burgdorferi, Clostridium perfringens, Peptococcus niger, Propionibacterium acnes, Bacteroides melaninogenicus;

- mycobacteria: Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium avium complex (MAC): Mycobacterium avium, Mycobacterium intracellulare;

The production of beta-lactamase does not affect the activity of clarithromycin.

Most strains of staphylococcus aureus resistant to methicillin and oxacillin are resistant to clarithromycin.

Clarithromycin exerts its action in vitro and for most strains of the following microorganisms (however, the safety and efficacy of using clarithromycin in clinical practice is not supported by clinical studies and the practical significance remains unclear):

- aerobic Gram-positive microorganisms: Streptococcus agalactiae, Streptococci (groups C, F, G), Viridans group streptococci;

- aerobic gram-negative microorganisms: 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;

- Campylobacter: Campylobacter jejuni.

The main metabolite of clarithromycin in the human body is the microbiologically active metabolite 14-hydroxyclarithromycin.The microbiological activity of the metabolite is the same as that of the starting material, or 1-2 times weaker in respect of most microorganisms. The exception is N. influenzae, in respect of which the efficiency of the metabolite is twice as high. The starting material and its main metabolite exert either an additive or a synergistic effect on N. Influenzae in conditions in vitro and in vivo depending on the culture of the bacteria.

Pharmacokinetics:

Absorption is fast. Food slows down absorption, without significantly affecting bioavailability.

Ingestion clarithromycin well and quickly absorbed from the gastrointestinal tract. Bioavailability is 50-55%. The connection with plasma proteins is 65-75%.

After a single dose, two peaks of maximum concentration are recorded. The second peak is due to the ability of the drug to concentrate in the gallbladder, followed by a gradual or rapid intake into the intestine and absorption.

After oral administration of 20-30% of the accepted dose of clarithromycin is rapidly hydroxylated in the liver by cytochrome isoenzymes CYP3A4, CYP3A5 and CYP3A7 with formation of the main metabolite of 14 (K) -hydroxyclarithromycin.

With a regular intake of 250 mg / day, the equilibrium concentration (C_ss) of clarithromycin and its main metabolite is 1 μg / ml and 0.6 μg / ml, respectively, the half-life (T_1/2) - 3-4 hours and 5-6 hours, respectively. When the dose is increased to 500 mg / day C_ssclarithromycin and its metabolite is 2.7-2.9 μg / ml and 0.83-0.88 μg / ml, respectively, the half-life is 4.8-5 hours and 6.9-8.7 hours, respectively.

In therapeutic concentrations, it accumulates in the lungs, skin and soft tissues (concentrations 10 times higher than serum levels.

It is excreted by the kidneys and intestines (20-30% unchanged, the rest in the form of metabolites). With a single admission of 250 mg and 1200 mg of kidneys, 37.91% and 46% are removed, the intestine - 40.2% and 29.1% respectively.

Pharmacokinetics in special clinical cases

In patients with moderate and severe impairment of liver function, but with a preserved renal function, no clarithromycin dose adjustment is required, C_ss and systemic clearance of clarithromycin do not differ from these indicators in healthy patients. C_ss 14-hydroxyclarithromycin in people with impaired liver function is lower than in healthy people.

In patients with impaired renal function increases with_mOh and C_min in blood plasma, T_1/2, area under the curve "concentration - time" (AUC) of clarithromycin and 14-hydroxyclarithromycin. The elimination constant and excretion by the kidneys decrease. The degree of changes in these parameters depends on the degree of impaired renal function.

In elderly patients the level of clarithromycin and 14-hydroxy-clarithromycin in the blood is higher, and excretion is slower than in young people. Changes in pharmacokinetics in elderly patients are primarily related to changes in the clearance of creatinine and the functional state of the kidneys, and not with the age of the patients.

C_ss clarithromycin and 14-hydroxyclarithromycin in patients with HIV infectionwho received clarithromycin in usual doses (500 mg twice a day) were similar to those in healthy people. However, when using clarithromycin at higher doses, which may be required for the treatment of mycobacterial infections, the concentrations of antibiotic can significantly exceed the usual ones. In patients with HIV infection who took clarithromycin at a dose of 1 g per day and 2 g / day in 2 doses, the maximum equilibrium concentration was usually 2-4 μg / ml and 5-10 μg / ml, respectively.When using the drug at higher doses, an increase in T1/2 compared with that of healthy people who received clarithromycin in usual doses. Increase in plasma concentrations and duration of T1/2 with the appointment of clarithromycin in higher doses is consistent with the known non-linearity of the pharmacokinetics of the drug.

Combined treatment with omeprazole

When appointing clarithromycin 500 mg 3 times a day in combination with omeprazole at a dose of 40 mg per day, there is an increase in T1/2 and AUC_0-24 omeprazole. In all patients receiving combination therapy, compared with those receiving one omeprazole, there was an increase AUC_0-24 Omeprazole by 89% and omeprazole by 34%. In clarithromycin FROM_mOh, Cmin and AUC_0-8 increased by 10%, 27% and 15%, respectively, compared with the data when only clarithromycin without omeprazole. In the equilibrium state, the concentrations of clarithromycin in the gastric mucosa 6 hours after admission in the group receiving the combination of drugs were 25 times greater than those in those receiving one clarithromycin. Clarithromycin concentration in tissues stomach after 6 hours after taking two drugs were 2 times higher than the data obtained in the group of patients who received one clarithromycin.

Indications:

Treatment of infectious-inflammatory diseases caused by pathogens sensitive to clarithromycin:

- Infections of the lower respiratory tract (bronchitis, community-acquired pneumonia);

- infections of the upper respiratory tract (pharyngitis, tonsillitis, sinusitis); ,

- infections of the skin and soft tissues (folliculitis, erysipelas);

- common mycobacterial infections caused by Mycobacterium avium and Mycobacterium intracellulare;

- prevention of the spread of infection caused by Mycobacterium avium complex (MAC);

- for eradication Helicobacter pylori and a decrease in the frequency of recurrences of duodenal ulcers;

- odontogenic infections.

Contraindications:

Hypersensitivity to clarithromycin (including other macrolides) and other ingredients, porphyria, simultaneous astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, midazolam for oral administration, alprazolam, triazolam, severe chronic renal failure (clearance creatinine less than 30 ml / min), sucrose deficit / isomaltose, fructose intolerance, glucose-galactose malabsorption, lactation, children under 3 years.

Carefully:

Renal and / or hepatic insufficiency, myasthenia gravis gravis, simultaneous administration of drugs metabolized by the liver, simultaneous reception of colchicine, pregnancy.

Pregnancy and lactation:

The use of the drug during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.

Clarithromycin excreted in breast milk, so if you need to prescribe the drug during lactation, breastfeeding should stop.

Dosing and Administration:

Inside, regardless of food intake.

Adults and children over 12 years of age and / or with a body weight of more than 33 kg usually appoint 250 mg every 12 hours. The course of treatment usually lasts for 7-14 days.

With pharyngitis and tonsillitis caused by S.pyogenes - 250 mg for 10 days every 12 hours.

In acute sinusitis - 500 mg for 14 days every 12 hours.

With exacerbation of chronic bronchitis caused by N. influenzae - 500 mg for 7-14 days every 12 hours, caused by H.parainfluenzae - 500 mg for 7 days every 12 hours caused by M. Catarrhalis, S. pneumonia - 250 mg for 7-14 days every 12 hours.

With community-acquired pneumonia caused by N. influenzae - 250 mg for 7 days every 12 hours caused by S. pneumonia, FROM. pneumonia, M. pneumonia - 250 mg for 7-14 days every 12 hours.

In uncomplicated infections of the skin and subcutaneous tissue caused by S. Aureus, S. Pyogenes - 250 mg for 7-14 days every 12 hours.

For the prevention and treatment of infections caused by Mycobacterium avium complex (MAC), clarithromycin appoint 500 mg twice a day. Duration of treatment is 6 months or more. The maximum daily dose is 1 g.

In odontogenic infections, the dose of clarithromycin is 250 mg twice a day for 5 days.

For eradication N. pylori prescribe a combination therapy with three drugs. The first scheme: clarithromycin - 500 mg twice a day, lansoprazole - 30 mg twice a day and amoxicillin - 1 g 2 times a day for 10 days. The second scheme: clarithromycin - 500 mg twice a day, amoxicillin - 1 g 2 times a day and omeprazole - 20 mg twice a day for 10 days.

It is also possible to use combination therapy with two drugs. Clarithromycin - 500 mg 3 times daily in combination with omeprazole at a dose of 40 mg per day for 14 days, with the appointment within the next 14 days of omeprazole at a dose of 20 mg per day.

Children from 3 to 12 years old clarithromycin appoint a daily dose of 15 mg / kg, divided into 2 doses for 10 days.The maximum daily dose is 1 g.

In patients with chronic renal insufficiency with creatinine clearance less than 30 ml / min or with a serum creatinine content of more than 290 μmol / l (3.3 mg / 100 ml), the dose should be halved or doubled between doses. The maximum duration of treatment in patients of this group is 14 days.

Side effects:

Allergic reactions: skin rash, itching, urticaria, anaphylactic reactions, skin hyperemia, Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the central nervous system: headache, dizziness, anxiety, insomnia, confusion, disorientation, hallucinations, depersonalization, a sense of fear, psychosis, "nightmarish" dreams, depression.

From the nervous system: convulsions.

From the urinary system: interstitial nephritis.

From the digestive system: dyspepsia, nausea, vomiting, gastralgia, diarrhea, stomatitis, glossitis, candidiasis of the oral mucosa, discoloration of the tongue and teeth, acute pancreatitis, increased activity of "liver" transaminases, hepatocellular and cholestatic hepatitis, cholestatic jaundice,pseudomembranous colitis, hepatic insufficiency with a lethal outcome mainly on the background of severe co-morbidities and / or concomitant drug therapy.

From the hematopoiesis: thrombocytopenia (unusual bleeding, hemorrhage).

From the sense organs: noise, ringing in the ears, change in taste, loss of hearing, after the withdrawal of the drug, impaired sense of smell.

From the side of the cardiovascular system: ventricular tachycardia, including "pirouette" type, flutter and ventricular fibrillation, lengthening of the interval QT on an electrocardiogram.

Laboratory indicators: leukopenia, hypercreatininaemia, hypoglycemia (including the simultaneous use of hypoglycemic drugs).

Other: myalgia, secondary infections (development of resistance of microorganisms).

Overdose:

Symptoms: abdominal pain, confusion, nausea, vomiting, diarrhea.

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

Interaction:

When co-administration of clarithromycin and drugs, primarily metabolized by the isoenzyme CYP3A, there may be a mutual increase in their concentrations, which may enhance or prolong both the therapeutic and side effects. Contraindicated joint administration with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, alprazolam, midazolam, triazolam.

Caution is prescribed with carbamazepine, cilostazol, cyclosporine, disopyramide, lovastatin, methylprednisolone, omeprazole, indirect anticoagulants (including warfarin), quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, vinblastine, phenytoin, theophylline and valproic acid (metabolized via other isoenzymes of cytochrome P450). It is necessary to adjust the dose of the drug and control the concentration in the blood.

When co-administered with cisapride, pimozide, terfenadine and astemizole, it is possible to increase the concentration of the latter in the blood, lengthening the interval QT, the occurrence of arrhythmia, including ventricular tachycardia, including "pirouette" and ventricular fibrillation.

When combined with ergotamine and dihydroergotamine, acute poisoning with drugs of the ergotamine group (vascular spasm, ischemia of limbs and other tissues,including the central nervous system).

Efavirenz, nevirapine, rifampicin, rifabutin and rifapentin (inducers of cytochrome P450) reduce the concentration of clarithromycin in plasma and weaken its therapeutic effect, and, at the same time, increase the concentration of 14-hydroxyclarithromycin.

With the simultaneous administration of fluconazole at a dose of 200 mg / day and clarithromycin at a dose of 1 g / day, an increase C_ss and AUC clarithromycin by 33% and 18%, respectively, correction of the dose of clarithromycin is not required.

With the simultaneous administration of ritonavir 600 mg / day and clarithromycin 1 g / day, a decrease in the metabolism of clarithromycin (an increase in C_mOh by 31%, C_ss by 182% and AUC by 77%), complete suppression of the formation of 14-hydroxyclarithromycin. In patients with chronic renal failure (CRF), dose adjustment is necessary: at a QC of 30-60 ml / min, the dose of clarithromycin should be reduced by 50%, with a CK 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. ECG monitoring is required (interval increase QT), serum concentrations of these drugs.

Clarithromycin increases the concentration of HMG-CoA reductase inhibitors (lovastatin, simvastatin) - the risk of rhabdomyolysis.

With the use of clarithromycin and omeprazole, an increase C_max, AUC and T_1/2 omeprazole by 30%, 89% and 34%, respectively. The average pH in the stomach for 24 hours was 5.2 with only omeprazole and 5.7 with omeprazole together with clarithromycin.

With the use of clarithromycin and indirect anticoagulants, the effect of the latter is possible.

When using clarithromycin with sildenafil, tadalafil or vardenafil (PDE-5 inhibitors), an increase in the inhibitory effect on PDE is possible. It may be necessary to reduce the dose of PDE-5 inhibitors.

With the joint appointment of clarithromycin with theophylline and carbamazepine, an increase in the concentration of the latter in the systemic circulation is possible.

When using clarithromycin with tolterodine in patients with slow metabolism through CYP2D6, a dose reduction of tolterodine may be required.

With the simultaneous administration of clarithromycin (1 g / day) with midazolam (oral), an increase AUC midazolam 7 times.It is necessary to avoid the combined oral administration of clarithromycin and midazolam, etc. benzodiazepines, which are metabolized CYP3A (triazolam and alprazolam). When using midazolam (intravenous) and clarithromycin, a dose adjustment may be required. The same precautions should be applied to other benzodiazepines, which are metabolized by isoenzymes CYP3A. For benzodiazepines, the excretion of which does not depend on isoenzymes CYP3A (temazepam, nitrazepam, lorazepam), clinically significant interaction with clarithromycin is unlikely.

When taking clarithromycin with colchicine, the effect of colchicine may be enhanced. It is necessary to monitor the possible development of clinical symptoms of colchicine intoxication, especially in elderly patients and patients with chronic renal failure (fatal cases have been reported).

With the joint administration of clarithromycin and digoxin, the concentration of digoxin in the serum should be carefully monitored (possibly increasing its concentration and the development of potentially fatal arrhythmias).

Simultaneous administration of zidovudine orally to HIV-infected adults and clarithromycin tablets may lead to a decrease in equilibrium concentrations of zidovudine. Given the fact that clarithromycin, probably changes the absorption of an orally administered zidovudine, this interaction is largely avoided when taking clarithromycin and zidovudine at different hours of the day (with an interval of at least 4 hours).

With the simultaneous administration of clarithromycin (1 g / day) and atazanavir (40 mg / day), an increase AUC atazanavir by 28%, clarithromycin by 2 times, decrease AUC 14-hydroxyclarithromycin by 70%. In patients with creatinine clearance from 30 to 60 ml / min, the dose of clarithromycin should be reduced by 50%. Clarithromycin in doses exceeding 1 g / day, can not be administered together with protease inhibitors.

With the joint administration of clarithromycin and itraconazole, a mutual increase in the concentration of drugs in the plasma is possible. For patients who simultaneously take itraconazole and clarithromycin, careful observation is necessary because of the possible increase or lengthening of the pharmacological effects of these drugs.

With concurrent administration of clarithromycin (1 g / day) and saquinavir (in soft gelatin capsules, 1200 mg 3 times per day), an increase AUC and C_ss saquinavir by 177% and 187%, respectively, and clarithromycin by 40%.When co-prescribing these drugs for a limited time at the doses indicated above, dose adjustment is not required.

With a joint admission with verapamil it is possible to lower blood pressure, bradyarrhythmia and lactic acidosis.

Special instructions:

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

Caution is prescribed against the background of 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 indirect anticoagulants, prothrombin time should be monitored.

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

If a severe and prolonged 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.

Effect on the ability to drive transp. cf. and fur:

Care should be taken when driving vehicles, mechanisms and when carrying out work requiring rapidity of psychomotor reactions.

Form release / dosage:

Film coated tablets, 250 mg and 500 mg.

Packaging:

For 5, 7 or 10 tablets in a contour mesh package.

1, 2 contoured cell packs together with instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000481

Date of registration:18.05.2010 / 06.12.2017

Expiration Date:Unlimited

The owner of the registration certificate:BIOKOM TECHNOLOGY, LLC BIOKOM TECHNOLOGY, LLC Republic of Belarus

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Representation: & nbspBIOKOM, CJSCBIOKOM, CJSC

Information update date: & nbsp24.01.2018

Illustrated instructions

Instructions

Clarithrosin® (Clarithrosin®)