Kispar - instructions for use, doses, side effects, contraindications

Oval, biconvex tablets covered with a film coating of white or almost white color, with a risk on one side and a firm impression on the other. On the fracture, two layers of white or almost white are visible.

Pharmacotherapeutic group:Antibiotic-macrolide

ATX: & nbsp

J.01.F.A.09 Clarithromycin

Pharmacodynamics:

Semisynthetic macrolide antibiotic of broad spectrum of action. Disrupts the synthesis of the protein of microorganisms (binds to 50S subunit of the ribosome membrane of a microbial cell).It acts on extracorporeal and intracellular pathogens. The activity of clarithromycin against most strains of the following microorganisms is proved as 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) - complex, including: Mycobacterium avium and Mycobacterium intracellulare;

- Helicobacter pylori.

Beta-lactamases do not affect the activity of clarithromycin.

Activity of clarithromycin in vitro:

- aerobic Gram-positive microorganisms: Listeria monocytogenes, Streptococcus agalactiae, Streptococci groups C, F, G, Streptococci groups viridans;

- 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;

- Campylobacteria: Campylobacter jejuni.

Microbiologically active metabolite of clarithromycin - 14 (R) -hydroxyclamirithromycin, is twice as active as the parent compound with respect to Haemophilus influenzae. Clarithromycin and its metabolite in combination can have both additive and synergistic effects on Haemophilus influenzae in vitro and in vivo, depending on the strain of the bacteria.

Most strains of staphylococci, resistant to methicillin and oxacillin, are resistant to clarithromycin.

It is possible to develop cross-resistance to clarithromycin and other antibiotics of the macrolide group, as well as to lincomycin and clindamycin.

Pharmacokinetics:

Absorption is fast. Food slows down absorption, without significantly affecting bioavailability. Bioavailability of tablets 250 mg - 50%. The connection with plasma proteins is 65-75%. After a single dose, 2 peaks of the maximum equilibrium concentration (C_mOh). The second peak is due to the ability of the drug to accumulate in the gallbladder, followed by a gradual or rapid intake into the intestine and absorption. Time to reach the maximum equilibrium concentration (TC_mOh) with the reception of 250 mg - 2-3 hours.

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 - 14 (R) -hydroxyclamirithromycin, which has a pronounced antimicrobial activity against Haemophilus influenzae. Is an inhibitor of isoenzymes CYP3A4, CYP3A5 and CYP3A7.

With a regular intake of 250 mg / day, the equilibrium concentrations of the unchanged drug and its main metabolite are 1.0 and 0.6 μg / ml, respectively; half-life (T1/2) - 3-4 and 5-6 hours respectively. When the dose is increased to 500 mg / day, the equilibrium concentrations of the unchanged drug and its metabolite in plasma are 2.7-2.9 and 0.83-0.88 μg / ml, respectively; T1/2 - 4.8-5 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).

It is excreted by the kidneys and intestines (20-30% - in unchanged form, the rest - in the form of metabolites). With a single admission of 250 and 1200 mg, kidneys produce 37.9 and 46%, intestines - 40.2 and 29.1%, respectively.

In chronic renal failure (CRF), the TC increases_mOh, FROM_max and AUC clarithromycin and its metabolite.

Indications:

Infections caused by microorganisms sensitive to clarithromycin:

- infection of the upper respiratory tract (pharyngitis, tonsillitis, sharp frayrhythm, acute sinusitis);

- infections of the lower respiratory tract (bronchitis, including exacerbation of chronic bronchitis, community-acquired bacterial and atypical pneumonia);

- uncomplicated skin and soft tissue infections (folliculitis, furunculosis, impetigo, wound infection);

- prevention and treatment of disseminated infection caused by Mycobacterium avium and Mycobacterium intracellulare;

- duodenal ulcer (for eradication H.pylori in combination therapy with proton pump inhibitors).

Contraindications:

- Hypersensitivity to clarithromycin, other antibiotics of the macrolide group or components of the drug;

- children under 12 years of age or weighing less than 33 kg;

- porphyria;

- simultaneous administration of ergotamine and other ergot alkaloids;

- simultaneous administration of cisapride, pimozide, astemizole, terfenadine;

- simultaneous administration of midazolam for oral administration, alprazolam, triazolam;

- lactation period.

Carefully:

- Severe renal impairment (creatinine clearance (CK) <30 mL / min), with or without disturbed liver function;

- myasthenia gravis gravis;

- simultaneous reception of drugs metabolized by the liver;

- simultaneous reception of colchicine;

- pregnancy.

Pregnancy and lactation:

The use of clarithromycin in the first trimester of pregnancy is contraindicated.

Use in the II and III trimesters of pregnancy is only possible if the intended benefit to the mother exceeds the potential risk forthe fetus.

If it is necessary to use clarithromycin during lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside, regardless of food intake.

Adults and children over 12 years of age or with a body weight of more than 33 kg:

- with pharyngitis and tonsillitis caused by S. pyogenes: 250 mg daily for 10 days every 12 hours;

- with 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 N. parainfluenzae: 500 mg for 7 days every 12 hours caused by M. catarrhalis, S. pneumoniae: for 250 mg for 7-14 days every 12 hours;

- with community-acquired pneumonia caused by H. influenzae: 250 mg for 7 days, every 12 hours, caused by S. pneumoniae, FROM. pneumoniae, M. pneumoniae: 250 mg for 7-14 days every 12 hours;

- with 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 treatment and prevention of infections caused by the complex Mycobacterium avium, designate an interior of 500 mg 2 timebut per day. Maximum stheaccurateI'm d1000 mg. Duration of treatment - 6 months or more.

- with the purpose of eradication Helicobacter pylori and reduce the risk of recurrence of duodenal ulcer, the following schemes of application are possible:

Scheme of triple therapy: clarithromycin 500 mg / lansoprazole 30 mg / amoxicillin 1000 mg - 2 times a day (with an interval of 12 hours), the course of treatment is 10-14 days.

Scheme of triple therapy: clarithromycin 500 mg / omeprazole 20 mg / amoxicillin 1000 mg - 2 times a day (with an interval of 12 hours), the course of treatment is 10 days.

Scheme of triple therapy: clarithromycin 500 mg / lansoprazole 30 mg / metronidazole 400 mg - 2 times a day (with an interval of 12 hours), the course of treatment is 7-10 days

Double therapy scheme: clarithromycin 500 mg 3 times a day (with an interval of 8 hours), omeprazole Inside 40 mg once a day (taken every day in the morning). The course of treatment is 14 days.

In patients with chronic renal insufficiency (CC less than 30 ml / min or serum creatinine concentrations greater than 3.3 mg / 100 ml), the dose is reduced by a factor of 2, or the interval between administrations is increased 2-fold. The maximum duration of treatment for patients in this group is 14 days.

Side effects:

From the nervous system: headache, dizziness, anxiety, insomnia, "nightmarish" dreams, convulsions, depression, disorientation, hallucinations, psychosis, depersonalization, confusion.

From the digestive system: dyspepsia, nausea, gastralgia, diarrhea, stomatitis, glossitis, candidiasis of the oral mucosa, language change color and teeth, acute pancreatitis, elevated "liver" enzymes, hepatocellular and cholestatic hepatitis, cholestatic jaundice, pseudomembranous colitis, hepatic failure with lethal outcome, mainly on the background of severe comorbidities and / or concomitant drug therapy.

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

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

On the part of the organs of hematopoiesis: thrombocytopenia (unusual bleeding, hemorrhage).

From the side of the urinary system: interstitial nephritis.

Change in laboratory indicators: leukopenia, hypercreatininaemia, hypoglycemia (including the simultaneous use of hypoglycemic drugs). Allergic reactions: skin rash, itching, urticaria, skin hyperemia, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis, anaphylactic reactions.

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

Overdose:

Symptoms: abdominal pain, nausea, vomiting, diarrhea.

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

Interaction:

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

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

When combined with ergotamine and dihydroergotamine, acute poisoning with drugs of the ergotamine group (vascular spasm, ischemia of extremities and other tissues, including CNS) is possible.

With caution appoint with carbamazepine, cilostazolum, cyclosporin, disopyramide, lovastatin, methylprednisolone, indirect anticoagulants (including warfarin), quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, vinblastine, phenytoin, theophylline and valproic acid (metabolized through other isozymes cytochrome P450). It is necessary to adjust the dose of medicines and control the concentration in the blood.

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 daily and clarithromycin at a dose of 1 g / day, an increase in the equilibrium concentrationCss) and the area under the curve (AUC) of 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_max by 31%, Css at 182% and AUC by 77%), complete suppression of the formation of 14-hydroxyclarithromycin.

In patients with chronic renal insufficiency, dose adjustment is necessary: with a QC of 30-60 ml / min, the dose of clarithromycin should be reduced by 50%, with a QC of less than 30 ml / min - by 5%.

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 (PDE5 inhibitors), it is possible to increase the inhibitory effect on PDE. It may be necessary to reduce the dose of PDE5 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 low isoenzyme activity CYP2D6, a dose reduction of tolterodine in the presence of clarithromycin (an inhibitor of isoenzymes CYP3A).

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, as well as other benzodiazepines, which are metabolized by isoenzymes CYP3A (triazolam and alprazolam). When using midazolam - (intravenously) and clarithromycin may require dose adjustment.

TakiThe 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 reception of clarithromycin (normal-release tablets) and zidovudine in adult HIV-infected patients may lead to a decrease Css zidovudine. It is necessary to select doses of clarithromycin and zidovudine. This type of interaction is not found in HIV-infected children receiving clarithromycin in the form of a suspension together with zidovudine.

With the simultaneous administration of clarithromycin (1 g / day) and atazanavir (400 mg / day), an increase AUC atazanavir by 28%, clarithromycin by 2 times, decrease AUC 14-hydroxy-clarithromycin at 70%. In patients with KK 30-60 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 enhancement or extension of pharmacological effects.

With concurrent administration of clarithromycin (1 g / day) and saquinavir (in soft gelatin capsules, 1200 mg 3 times a day), an increase AUC and Css saquinavir by 177% and 187%, respectively, and clarithromycin by 40%. When these two drugs are co-administered for a limited time, dose adjustment is not required.

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

Special instructions:

Reception of clarithromycin in tablets in children younger than 12 years is not recommended. In such cases, a suspension of clarithromycin (for children) is used.

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 combined use with warfarin or other indirect anticoagulants, prothrombin time should be monitored.

With the simultaneous use of clarithromycin and digoxin, serum concentration of digoxin 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:Patients receiving clarithromycin, care should be taken when driving a car and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions due to the possibility of side effects from the nervous system.

Form release / dosage:

Tablets, film-coated, 250 mg.

Packaging:

6 tablets per blister of PVC/ aluminum foil.

For 1 or 2 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

In tightly closed containers, in a dry, protected from light place at a temperature of no higher than 20 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001296

Date of registration:28.11.2011

Expiration Date:28.11.2016

The owner of the registration certificate:Suzhou Dunrais Pharmaceutical Co., Ltd. Ltd.Suzhou Dunrais Pharmaceutical Co., Ltd. Ltd. China

Manufacturer: & nbsp

SUZHOU DAWNRAYS PHARMACEUTICALS, Co.Ltd. China

Representation: & nbspInstitute of Health CJSCInstitute of Health CJSC

Information update date: & nbsp11.01.2018

Illustrated instructions

Instructions

Kispar® (Kispar®)