Klacid instructions for use for children tablets. Experts give unequivocal reviews: Klacid is effective. Indications for taking Klacid

Instructions

Tradename

Klacid 

International nonproprietary name

Clarithromycin

Dosage form

Film-coated tablets 500 mg

Compound

One tablet coated, contains:

active substance - clarithromycin 500 mg

Excipients: croscarmellose sodium, microcrystalline cellulose, silicon dioxide,povidone, stearic acid, magnesium stearate,talc.

shell composition: hypromellose, sorbitan monooleate, propylene glycol, titanium dioxide (E171), vanillin, yellow dye (quinoline yellow) (E 104)aluminum varnish, hydroxypropylcellulose, sorbic acid.

Description

Oval-shaped, film-coated tablets of pale yellow color.

Pharmacotherapeutic group

Antibacterial drugs for systemic use. Macrolides, lincosamides and streptogramins. Macrolides. Clarithromycin.

ATX code J01 FA09

Pharmacological properties

PharmacokineticsAbsorption

Pharmacokinetics of the drug Klacid® has been widely studied in experimental animals and adults. These studies showed that clarithromycin is completely and rapidly absorbed. Absolute bioavailability is about 50%. When taking the drug multiple times, unexpected accumulation is not detected or is detected in small quantities. At the same time, the nature of metabolism in the human body does not change. Eating immediately before administration of the drug increases the bioavailability of clarithromycin by an average of 25%. In general, this increase is insignificant and has little clinical significance at recommended dosing regimens. Therefore, clarithromycin can be prescribed both with and before meals.

Distribution, biotransformation and elimination

In vitro

Research in vitroshowed that clarithromycin binds to human plasma proteins at an average level of about 70%, with clinically relevant concentrations ranging from 0.45 μg/ml to 4.5 μg/ml. The decrease in binding to 41% at 45.0 μg/mL suggested that binding sites could become saturated, but this only occurred at concentrations well above therapeutic drug concentrations.

Results from animal studies showed that clarithromycin levels in all tissues except the central nervous system were several times higher than circulating levels of the drug. The highest concentrations were usually found in the liver and lungs, where the tissue/plasma ratio reached 10-20.

Healthy subjects

With a dosage regimen of 250 mg 2 times a day, the equilibrium maximum concentration (C max ) was achieved after 2-3 days and averaged approximately 1 μg/ml for clarithromycin and 0.6 μg/ml for 14-OH-clarithromycin, respectively. The half-life periods of the parent drug and metabolite are 3-4 hours and 5-6 hours, respectively. With a dosage regimen of 500 mg 2 times a day C max clarithromycin and 14-OH-clarithromycin in an equilibrium state was achieved after taking the 5th dose of the drug. After taking the 5th and 7th doses C max clarithromycin at steady state averaged 2.7 and 2.9 μg/ml, and 14-OH-clarithromycin 0.88 and 0.83 μg/ml, respectively. The half-life of the parent drug at a dose of 500 mg was 4.5-4.8 hours, and 14-OH-clarithromycin - 6.9-8.7 hours. At steady state, the concentration of 14-OH-clarithromycin does not increase proportionally with the dose of clarithromycin, and the half-lives of clarithromycin and its hydroxylated metabolite tended to be prolonged when higher doses were used. This nonlinear pharmacokinetics of clarithromycin, together with the cumulative reduction in the formation of 14-hydroxylation and N-demethylation products at higher doses, indicates that the nonlinear metabolism of clarithromycin becomes more pronounced at higher doses.

In adults who received a single dose of clarithromycin 250 mg or 1200 mg orally, excretionwith urine amounted to 37.9% of the low dose of the drug and 46.0% of its high dose. Intestinal excretion was 40.2% and 29.1% of the corresponding clarithromycin doses (including a subject with only one fecal sample containing 14.1% drug).

Patients

Clarithromycin and its 14-OH metabolite are easily distributed in tissues and body fluids. Limited data from a study in a small number of patients suggest that the concentration of clarithromycin in the cerebrospinal fluid after oral administration is negligible (specifically, only 1-2% of the serum concentration in the cerebrospinal fluid in the presence of normal blood-brain barrier permeability ). Tissue concentrations are usually several times higher than serum concentrations.

Liver dysfunction

In a study comparing a group of healthy volunteers with a group of patients with hepatic impairment who took 250 mg immediate-release clarithromycin twice daily for two days and a single dose of 250 mg on the third day, steady-state plasma concentrations and systemic clearance of clarithromycin were not significantly different in both groups. In contrast, equilibrium concentrations of 14- OH -metabolites were noticeably lower in the group of patients with impaired liver function. This reduced metabolic clearance of the parent compound by 14-hydroxylation was partially offset by increased renal clearance of the parent drug, resulting in comparable steady-state concentrations of the parent drug in patients with hepatic impairment and healthy volunteers. These results indicate that no dose adjustment is required in individuals with moderate to severe liver damage but normal renal function.

Renal dysfunction

A study was conducted to evaluate and compare the pharmacokinetic profile of multiple 500 mg oral doses of immediate-release clarithromycin in patients with normal and reduced renal function. Plasma concentrations, half-life, Cmax and Cmin for clarithromycin and its 14- OH -metabolites were higher, and AUC - more in patients with impaired renal function. The elimination constant and urinary excretion were lower. The degree of change in these parameters depends on the degree of renal dysfunction: the more severe the kidney damage, the more significant the difference (see section “Dosage and Administration”).

Elderly patients

A study was also conducted to evaluate and compare the safety and pharmacokinetic profile of clarithromycin 500 mg when administered orally in multiple doses in healthy elderly male and female patients and healthy young male adults. In the group of elderly people, plasma concentrations of the parent drug and 14- OH -metabolites were higher, and excretion was slower than in the young group. However, no differences were found between the ratio of renal clearance and creatinine clearance. From these results it is concluded that any change in pharmacokinetics is related to renal function and not age per se.

Infections caused by Mycobacterium avium

Equilibrium concentrations of clarithromycin and 14- OH -clarithromycin in adult patients with HIV infection receiving clarithromycin at a dose of 500 mg every 12 hours were similar to those in healthy individuals. However, at higher doses that may be required to treat infections caused byMycobacterium avium, clarithromycin concentrations were significantly higher than those observed at usual doses. In adult HIV-infected patients taking the drug at a dose of 1000 and 2000 mg/day in two doses, the values Cmax clarithromycin at steady state varied from 2 to 4 μg/ml and from 5 to 10 μg/ml, respectively. The half-life at these higher doses was prolonged compared with that in healthy subjects receiving clarithromycin at usual doses. Higher plasma concentrations and prolonged half-life when clarithromycin is administered at these doses are associated with the nonlinear pharmacokinetics of the drug.

Use simultaneously with omeprazole

A pharmacokinetic study of clarithromycin at a dose of 500 mg 3 times a day and omeprazole 40 mg 1 time a day was conducted. When clarithromycin is administered alone at a dose of 500 mg every 8 hours, average values Cmax were approximately 3.8 μg/ml, and the average values Cmin were approximately 1.8 μg/ml. Average values AUC0-8 clarithromycin were 22.9 μg/h/ml. Tmax and the half-life of clarithromycin administered at a dose of 500 mg 3 times daily were 2.1 hours and 5.3 hours, respectively.

In the same study, when clarithromycin was administered at a dose of 500 mg 3 times a day with omeprazole 40 mg 1 time a day, an increase in half-life and AUC0-24 omeprazole. For all patients receiving combination therapy, the average values AUC0-24 omeprazole were 89% higher, and the harmonic mean T1/2 omeprazole - 34% higher than with omeprazole monotherapy. When prescribing clarithromycin with omeprazole Cmax, Cmin, and AUC0-8 clarithromycin increased by 10%, 27%, and 15%, respectively, compared with the values ​​achieved when clarithromycin was administered with placebo.

At steady state, clarithromycin concentrations in the gastric mucosa 6 hours after dosing in the clarithromycin/omeprazole group were approximately 25 times higher than those in the clarithromycin alone group. Mean gastric tissue concentrations of clarithromycin 6 hours after administration of clarithromycin with omeprazole were approximately 2 times higher than those observed with clarithromycin with placebo..

Pharmacodynamics

Clarithromycin is a semisynthetic macrolide antibiotic obtained by substitution CH3O -hydroxyl group ( OH ) group at the 6th position of the lactone ring of erythromycin. More precisely, clarithromycin is 6-O-methylerythromycin A. This antibiotic is a white or almost white powder with a bitter taste, practically odorless, virtually insoluble in water and slightly soluble in ethanol, methanol and acetonitrile. Its molecular weight is 747.96

Microbiology

Antibacterial effect of the drug Klacid® determined by itlinking with 5 OS -ribosomal subunit of sensitive bacteria and inhibitionprotein biosynthesis.The drug is highly effectivein vitro against standard strains of bacteria and strains isolated in clinical practice. It is highly effective against a wide range of aerobic and anaerobic gram-positive and gram-negative microorganisms. Minimum inhibitory concentrations (MIC) of clarithromycin on average per one log 2 dilution is lower than the MIC of erythromycin. Clarithromycinin vitro highly effective againstLegionella pneumophila AndMycoplasma pneumoniae . Clarithromycin acts bactericidal againstHelicobacter pylori, The activity of clarithromycin at neutral pH is higher than at acidic pH.In vitro And in vivodata indicate the high effectiveness of clarithromycin against clinically significant strains of mycobacteria. Research in vitro showed , what strains Enterobacteriaceae And Pseudomonas, like gram-negative bacteria that do not ferment lactose, they are insensitive to clarithromycin.

The activity of clarithromycin against most strains of the microorganisms listed below is shown asin vitro, and in clinical practice for the diseases listed in the “Indications for use” section.

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).

Mycobacteria :

Mycobacterium leprae,

Mycobacterium kansasii,

Mycobacterium chelonae,

Mycobacterium fortuitum,

Mycobacterium avium complex (MAC), which includes Mycobacterium avium, Mycobacterium intracellulare.

The production of beta-lactamases does not affect the effectiveness of clarithromycin.

Most methicillin- and oxacillin-resistant strains of staphylococci are not sensitive to clarithromycin.

Helicobacter:

H. pylori.

In cultures prepared before therapy,H. pylori and before starting treatment, the minimum inhibitory concentration was determined in 104 patients. Of these, clarithromycin-resistant strains were identified in 4 patientsH. pylori, 2 patients had strains with intermediate sensitivity, and 98 patients had isolatesH. pylori were sensitive to clarithromycin.

The following data is availablein vitro, but their clinical significance is unknown . Clarithromycin shows activityin vitro against most strains of the following microorganisms; however, the safety and effectiveness of clarithromycin in the treatment of clinical infections caused by these microorganisms has not been confirmed in controlled clinical trials.

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 :

Bacteriodes melaninogenicus .

Spirochetes:

Borrelia burgdorferi ,

Treponema pallidum .

Campylobacter :

Campylobacter jejuni .

The main metabolite of clarithromycin in the human body is the microbiologically active metabolite 14- OH -clarithromycin. For most microorganisms, this metabolite is as active or 1-2 times less active than the parent compound, with the exception ofH. influenzae, in relation to which he is twice as active. Initial connection and 14- OH -metabolite cause an additive or synergistic effect in relation toH. influenzae in conditions in vitro And in vivo, depending on the strain of bacteria. Data obtained from experimental animal models of infection showed that clarithromycin is 2-10 times more active than erythromycin.

Indications for use

Clarithromycin is indicated for the treatment of infections caused by susceptible organisms:

Lower respiratory tract infections (bronchitis, pneumonia, etc.)

Upper respiratory tract infections (pharyngitis, sinusitis, etc.)

Skin and soft tissue infections (folliculitis, cellulitis, erysipelas, etc.)

Disseminated or localized mycobacterial infections caused byMycobacterium avium or Mycobacterium intracellulare, localized infections caused byMycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium kansasii;

For the prevention of dissemin oriented s infections caused by the complexMycobacterium avium (MAC) in HIV-infected patients with CD counts 4 -lymphocytes ≤ 100/mm 3 ;

For eradication H. pylori , helping to reduce relapses of duodenal ulcer

- treatment of odontogenic infections

Sensitivity tests

Quantitative methods that require zone diameter measurements provide the most accurate estimates of bacterial antimicrobial susceptibility. One recommended procedure for susceptibility testing uses disks impregnated with 15 μg of clarithromycin (Kirby-Bauer diffusion test); the diameter of the inhibition zone for this disk is correlated with the minimum inhibitory concentration values ​​for clarithromycin. The minimum inhibitory concentration is determined by dilution in broth or agar.

With these procedures, a susceptibility report from the laboratory indicates that the infecting organism is most likely to respond to therapy. A report with the word “resistant” indicates that the infecting organism will most likely not respond to therapy. A report with the words "intermediate sensitivity" indicates that the therapeutic effect of the drug may be questionable or that the organism will be susceptible if higher doses are used (intermediate sensitivity is also referred to as moderate sensitivity).

Please refer to your country or region specific information for absolute limit ranges for susceptibility, susceptibility and intermediate sensitivity.

Directions for use and doses

Adults

The usual recommended dose of clarithromycin for adults and children over 12 years of age is 250 mg tablet twice daily. For more severe infections, the dose can be increased to 500 mg twice daily. The usual duration of treatment is from 5 to 14 days, except for the treatment of community-acquired pneumonia and sinusitis, which require 6 to 14 days of therapy.

Mycobacterial infections

Treatment of disseminated MAC infections in patients with AIDS should continue as long as clinical and microbiological benefit is demonstrated. Clarithromycin should be used in combination with other antimycobacterial drugs.

Treatment for other non-tuberculous mycobacterial infections should be continued at the discretion of the treating physician.

Odontogenic infections

In the treatment of odontogenic infections, the usual dose isclarithromycin is250 mg 2 times a day for 5 days.

In patients with peptic ulcers caused byH. pylori - infection, clarithromycin can be prescribed at a dose of 500 mg 2 times a day in combination with other necessary antimicrobials and proton pump inhibitors for 7-14 days in accordance with national or international eradication guidelinesH. pylori .

Kidney failure

In patients with severe renal failure (creatinine clearance less than 30 ml/min), the dose of clarithromycin should be reduced by half and should be 250 mg 1 time per day or 250 mg 2 times per day for more severe infections. Treatment of these patients should not continue for more than 14 days.

Children

Use of the drug Klacid® has not been studied in children under 12 years of age.

Side effects

The most common and common adverse reactions during treatment with Klacid® adults and children are abdominal pain, diarrhea, nausea, vomiting and taste distortion. These adverse reactions are usually mild and are consistent with the known safety profile of macrolide antibiotics. During clinical studies, there were no significant differences in the incidence of these gastrointestinal adverse reactions between groups of patients who did or did not have mycobacterial infections.

Below are the adverse reactions that occurred during clinical trials and during post-marketing application of various dosage forms and dosages of the drug Klacid® . Adverse reactions at least, probably related to clarithromycin, distributed by organ system and frequency of occurrence: very common (≥1/10), common (≥1/100 to<1/10), нечасто (≥ 1/1000 до <1/100), с неизвестной частотой (побочные реакции, выявленные при постмаркетинговом наблюдении, частоту определить невозможно из имеющихся данных). В пределах каждой группы по частоте побочные реакции представлены в порядке убывания тяжести проявлений, если тяжесть удалось оценить.

Often

phlebitis at the injection site 1

Often

≥ 1/100 to<1/10

Insomnia

Headache

Dysgeusia, taste distortion

Vasodilation 1

Nausea, abdominal pain, vomiting, dyspepsia, diarrhea

Abnormal liver function tests

Rash, hyperhidrosis

Pain at the injection site 1 , inflammation at the injection site 1

Infrequently

≥ 1/1000 to<1/100

Cellulite 1 , candidiasis, gastroenteritis 2

Infection 3 , vaginal infection

- leukopenia, neutropenia 4, thrombocythemia 3, eosinophilia 4

Anaphylactoid reactions 1 , hypersensitivity

Anorexia, loss of appetite

Anxiety, restlessness and agitation 3

Loss of consciousness 1, dyskinesia 1 , dizziness, drowsiness, tremor

Vertigo, hearing loss, ringing in the ears

Heart failure 1 , atrial fibrillation 1 , prolongation of the QT interval on the ECG, extrasystoles 1 , feeling of heartbeat

Asthma 1 , nose bleed 2 , pulmonary embolism 1

Esophagitis 1 , gastroesophageal reflux disease 2 , gastritis, proctalgia 2 , stomatitis, glossitis, bloating 4 , constipation, dry mouth, belching, flatulence

Cholestasis 4, hepatitis 4 , increased levels of ALT, AST, GGT 4

Bullous dermatitis 1 , itching, urticaria, maculopapular rash 3

Muscle spasms 3 , musculoskeletal rigidity 1, myalgia 2

Increased blood creatinine 1 , increased blood urea 1

Malaise 4, fever 3 , asthenia, chest pain 4, chills 4, fatigue 4

Change in albumin-globulin ratio 1 , increased levels of alkaline phosphatase in the blood 4 , increased levels of lactate dehydrogenase in the blood 4

Frequency unknown*

(frequency cannot be determined from available data)

Pseudomembranous colitis, erysipelas

Agranulocytosis, thrombocytopenia

Anaphylactic reactions, angioedema

Psychosis, confusion, depersonalization, depression, disorientation, hallucinations, nightmares, mania

Convulsions, ageusia, parosmia, anosmia, paresthesia

Hearing loss

Torsade de pointes ventricular tachycardia (torsade sde pointes ), ventricular tachycardia, ventricular fibrillation.

Hemorrhage

Acute pancreatitis, tongue discoloration, tooth discoloration

Liver failure, hepatocellular jaundice

Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction skin reaction with eosinophilia and systemic manifestations (DRESS), acne

Rhabdomyolysis 2**, myopathy

Renal failure, interstitial nephritis

Increased international normalized ratio, increased prothrombin time, change in urine color.

*Frequency unknown as these reactions were reported voluntarily from an unknown patient population. It is not always possible to accurately establish their frequency or causal relationship with taking the drug. Overall experience with clarithromycin is more than 1 billion patient days..

** In some reports of rhabdomyolysis, clarithromycin was administered concomitantly with other drugs known to be associated with rhabdomyolysis (such as statins, fibrates, colchicine, or allopurinol).

1. Reports of adverse reactions were only for the powder form for the preparation of solution for infusion.

2. Adverse reactions were reported only for the extended-release tablet formulation.

3. Reports of adverse reactions were only for the granule formulation for oral suspension.

4. Adverse reactions were reported only for the immediate-release tablet formulation.

The frequency, type and severity of adverse reactions in children are expected to be the same as in adults.

Patients with immune system disorders In patients with AIDS and other patients with compromised immune systems who have used high doses of clarithromycin for a long time to treat mycobacterial infections,It is not always possible to distinguish between adverse reactions associated with the use of the drug and symptoms of the underlying or concomitant diseases. In adult patients who received Klacid® at a daily dose of 1000 mg, the most common side effects were nausea, vomiting, taste disturbance, abdominal pain, diarrhea, rash, bloating, headache, constipation, hearing loss, increased levels of AST and ALT in the blood serum. Uncommon: dyspnea, insomnia and dry mouth. These immune-compromised patients were assessed for laboratory values ​​that were significantly different from the normative values ​​(i.e., extreme upper or lower limits) for specific tests. According to this criterion, 2-3% of patients who received 1000 mg of clarithromycin per day experienced significant increases in AST and ALT levels and significant decreases in white blood cell and platelet counts. A smaller percentage of patients also experienced increased blood urea levels.

Contraindications

Hypersensitivity to macrolide antibiotics or to any auxiliary components of the drug.

Concomitant use of clarithromycin and any of the following drugs is contraindicated: astemizole, cisapride, pimozide, terfenadine, as this may lead to prolongation of the QT interval and the development of arrhythmias, including ventricular tachycardia, ventricular fibrillation and torsade de pointes (TdP). Torsades de pointes) (see section "Drug interactions").

The simultaneous use of clarithromycin and ergot alkaloids (for example, ergotamine, dihydroergotamine) is contraindicated as this may lead to ergot alkaloid poisoning (see section "Drug Interactions").

Concomitant use of clarithromycin and midazolam for oral use is contraindicated (see section "Drug Interactions").

Clarithromycin should not be used in patients with a history of QT prolongation (congenital or known acquired QT prolongation) or ventricular arrhythmia, including torsade de pointes (TdP). Torsades de pointes) (see “Drug Interactions” and “Special Instructions”).

Clarithromycin should not be administered to patients with hypokalemia (risk of QT prolongation).

Clarithromycin should not be prescribed to patients who suffer from severe hepatic impairment with concomitant renal failure.

Clarithromycin should not be used concomitantly with HMG-CoA reductase inhibitors (statins) that are significantly metabolized by CYP3A4 (lovastatin or simvastatin) due to an increased risk of myopathy, including rhabdomyolysis (see section "Special Instructions").

Clarithromycin (and other strong CYP3A4 inhibitors) should not be used concomitantly with colchicine (see Drug Interactions and Precautions).

Co-administration with ticagrelor or ranolazine is contraindicated.

Children's age up to 12 years

Drug interactions

The use of the following medications is strictly contraindicated due to the potential for severe interaction effects

Cisapride, pimozide, astemizole and terfenadine .

Increased cisapride levels have been reported in patients receiving Klacid® and cisapride at the same time. This may lead to a longer interval QT and the appearance of arrhythmias, including ventricular tachycardia, ventricular fibrillation and ventricular tachycardia of the “pirouette” type (torsades de pointes). Similar effects have been observed in patients taking

Klacid ® and pimozide at the same time (see section “Contraindications”).

Macrolides affect the metabolism of terfenadine, causing increased levels of terfenadine in the blood, sometimes accompanied by arrhythmias such as increased interval QT , ventricular tachycardia, ventricular fibrillation and ventricular tachycardia of the “pirouette” type (torsades de pointes) (see section “Contraindications”). In a study involving 14 healthy volunteers, the simultaneous use of clarithromycin and terfenadine led to a 2-3-fold increase in the level of the acid metabolite terfenadine in the blood serum and an extension of the interval QT , which did not cause any clinically significant effect.

Similar effects were observed with the simultaneous use of astemizole and other macrolides.

Ergot alkaloids . Post-marketing studies show that concomitant use of clarithromycin and ergotamine or dihydroergotamine leads to ergot toxicity, manifested in the form of vasospasm, ischemia of the limbs and other tissues, including the central nervous system.Simultaneous administration of the drug Klacid® and ergot alkaloids are contraindicated (see section “Contraindications”).

Midazolam for oral use

With the simultaneous use of midazolam and clarithromycin tablets (500 mg twice a day), AUC midazolam increased 7-fold after oral administration of midazolam. The simultaneous administration of oral midazolam and clarithromycin is contraindicated (see section "Contraindications").

. Simultaneous use of the drugKlacid® with lovastatin or simvastatin is contraindicated (see section "Contraindications"), as they are significantly metabolized CYP3 A 4, and simultaneous treatment with clarithromycin causes an increase in their plasma concentrations, which increases the risk of developing myopathy and rhabdomyolysis. There are reports of cases of rhabdomyolysis in patients who simultaneously took clarithromycin with these statins. If the use of the drugKlacid® cannot be avoided, then taking lovastatin or simvastatin must be suspended while using the drugKlacid® .

Klacid® with statins. If the simultaneous use of the drugKlacid® and statins are unavoidable, it is recommended to prescribe the lowest reported dose of statin. A statin that is not metabolized should be considered. CYP3 A eg fluvastatin. Patients should be monitored for signs and symptoms of myopathy.

Effect of other drugs on Klacid ® . Drugs that induce CYP3 A (eg, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort) may accelerate the metabolism of clarithromycin. This may result in subtherapeutic levels of clarithromycin and reduced effectiveness. In addition, it may be necessary to monitor levels of other drugs that induce CYP3 A , which may increase due to the inhibitory effect of clarithromycin on CYP3 A (see also instructions for medical use of the corresponding inhibitor CYP3 A 4). Simultaneous use of rifabutin and the drug Klacid® resulted in increased rifabutin levels and decreased clarithromycin serum concentrations with an increased risk of uveitis.

The following drugs affect or are suspected to affect the serum concentrations of clarithromycin. Dosage adjustment may be required Klacid ® or considering alternative treatment options

Efavirenz, nevirapine, rifampicin, rifabutin and rifapentine

Strong inducers of the cytochrome metabolic system P 450, such as efavirenz, nevirapine, rifampicin, rifabutin and rifapentine, may accelerate the metabolism of clarithromycin, thereby reducing its plasma concentration while increasing the concentration of its active metabolite (14- OH -clarithromycin). Since the microbiological activity of clarithromycin and 14- OH -clarithromycin is different in relation to various bacteria, then simultaneous administration of the drugKlacid® and inducers of cytochrome P450 enzymes may interfere with the achievement of the desired therapeutic effect.

Etravirine : When taking etravirine, exposure to the drug Klacid® decreases, and the concentration of its active metabolite, 14- OH -clarithromycin, increases. Since 14- OH -clarithromycin is less active againstMycobacterium avium complex (MAC ), the overall effectiveness of the drug against a given pathogen may vary. For this reason, for treatment MAC Alternative treatment options should be considered.

Fluconazole

Coadministration of 200 mg fluconazole per day and 500 mg clarithromycin twice daily in 21 healthy volunteers resulted in an increase in the mean steady-state trough concentration of clarithromycin ( Cmin ) and area under the curve ( AUC ) by 33% and 18%, respectively.

Steady-state concentrations of the active metabolite 14-OH-clarithromycin did not change significantly with concomitant use of fluconazole. Drug dose adjustmentKlacid® not required.

Ritonavir

A pharmacokinetic study showed that co-administration of 200 mg ritonavir every eight hours and Klacid® 500 mg every 12 hours leads to a marked decrease in the metabolism of clarithromycin. Wherein Cmax clarithromycin increased by 31%, Cmin increased by 182%, AUC increased by 77% with simultaneous administration of ritonavir. Almost complete inhibition of the formation of 14- OH -clarithromycin. Due to the wide therapeutic range, reducing the dose of the drugKlacid® not required in patients with normal renal function. In patients with renal failure, dose adjustment is necessary: ​​for patients with creatinine clearance (CC) 30-60 ml/min dose of the drugKlacid® needs to be reduced by 50%. For patients with CC< 30 мл/мин дозу Клацид ® needs to be reduced by 75%. Doses of the drugKlacid® doses exceeding 1 g/day should not be used with ritonavir. Similar dose adjustments should be made in patients with renal impairment when ritonavir is used as a pharmacokinetic enhancer with other HIV protease inhibitors, including atazanavir and saquinavir (see section "Bidirectional drug interactions").

Influence drug Klacid ® for other drugs

Antiarrhythmic drugs .

In post-marketing practice, cases of ventricular tachycardia of the “pirouette” type have been recorded (torsades de pointes) while taking clarithromycin and quinidine or disopyramide.

When taking the drug simultaneouslyKlacid® With these drugs, it is recommended to carry out ECG monitoring for timely detection of interval prolongation QT . During drug therapyKlacid® serum concentrations of these drugs should be monitored. There are also reports of cases of hypoglycemia when taking clarithromycin and disopyramide simultaneously. When taking the drug simultaneouslyKlacid® AndDisopyramide should monitor blood glucose levels.

Oral hypoglycemic agents and insulin .

When used concomitantly with certain hypoglycemic agents such as nateglinide and repaglinide and drug Klacid® enzyme inhibition may occur CYP3 A clarithromycin, which can cause hypoglycemia. Close monitoring of glucose levels is recommended.

CYP3 A-related interactions .

Simultaneous use drug Klacid® , known as an enzyme inhibitor CYP3 A , and a drug that is primarily metabolized CYP3 A , may lead to an increase in the concentration of the latter in the blood plasma, which, in turn, may enhance or prolong its therapeutic effect and adverse reactions.

Caution should be exercised when using drug Klacid® in patients receiving drugs - substrates CYP3 A , especially if the latter have a narrow therapeutic range (eg carbamazepine) and/or are extensively metabolized by this enzyme.

Dose adjustments and, if possible, close monitoring of serum concentrations of metabolized drugs may be necessary. CYP3 A in patients who are simultaneously usingKlacid® .

The following drugs or groups of drugs are known or suspected to be metabolized by the same CYP3 A isoenzyme: alprazolam, astemizole, carbamazepine, cilostazol, cisapride, cyclosporine, disopyramide, horn alkaloids, lovastatin, methylprednisolone, midazolam, omeprazole, oral anticoagulants (for example, warfarin),atypical antipsychotics (eg quetiapine), pimozide, quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, terfenadine, triazolam and vinblastine,but this list is not complete. A similar mechanism of interaction was noted with the use of phenytoin, theophylline and valproate, which are metabolized by another isoenzyme of the cytochrome P system450 .

Omeprazole . There are results of a study on adult healthy volunteers who took Klacid at the same time® (500 mg every 8 hours) and omeprazole (40 mg per day). When taken simultaneously with the drug Klacid® an increase in the steady-state concentration of omeprazole in plasma was noted ( Cmax, AUC0-24 and t1/2 increased by 30%, 89% and 34%, respectively). Average value of the indicator pH in 24 hours in the stomach was 5.2 when taking omeprazole alone and 5.7 when taking omeprazole simultaneously with the drug Klacid® .

Sildenafil, tadalafil and vardenafil .

Each of these phosphodiesterase inhibitors is metabolized, at least in part, by CYP3 A, and CYP3 A may be inhibited by concomitantly administered clarithromycin. Simultaneous use of Klacid® and sildenafil, tadalafil or vardenafil may result in increased phosphodiesterase inhibitor exposure. When using these drugs simultaneously with Klacid® A dose reduction of sildenafil, tadalafil or vardenafil should be considered.

Theophylline, carbamazepine .

Results from clinical studies indicate that there is a small but statistically significant ( p ≤0.05) increase in circulating concentrations of theophylline or carbamazepine when taking any of these drugs simultaneously with Klacid® .

Tolterodine mainly metabolized 2 D6- isoform of cytochrome P 450 (CYP2 D 6). However, in patients without CYP2 D 6 metabolism occurs through CYP3 A . In this population, oppression CYP3 A leads to a significant increase in plasma concentrations of tolterodine. For these patients, a dose reduction of tolterodine may be necessary when used with inhibitors. CYP3 A such as Klacid® .

Triazolobenzodiazepines (eg, alprazolam, midazolam, triazolam).

When midazolam was coadministered with clarithromycin tablets (500 mg twice daily), the AUC of midazolam increased 2.7-fold when midazolam was administered intravenously. When intravenous use of midazolam with the drug Klacid® The patient's condition should be carefully monitored for timely dose adjustment.

The oromucosal route of administration of midazolam may preclude pre-systemic elimination of the drug, which is more likely to result in an interaction similar to that observed with intravenous midazolam rather than oral administration.

The same precautions should be taken when using other benzodiazepines that are metabolized by CYP3A, including triazolam and alprazolam. For benzodiazepines, the elimination of which does not depend on CYP3A (temazepam, nitrazepam, lorazepam), the development of a clinically significant interaction with the drug Klacid® unlikely.

There are post-marketing reports of drug interactions and central nervous system side effects (such as drowsiness and confusion) with concomitant use of clarithromycin and triazolam. The patient's condition should be monitored, taking into account the possibility of increased pharmacological effects on the central nervous system.

Interaction with other drugs

Colchicine

Colchicine is a substrate for both CYP3 A , and for the P-glycoprotein carrier protein ( pgp). It is known that Klacid® and other macrolides are inhibitors CYP3 A and P-glycoprotein. In case of simultaneous use of the drugKlacid® and colchicine, inhibition of P-glycoprotein and/or clarithromycin CYP3 A may result in increased colchicine exposure. Simultaneous use of the drugKlacid® and colchicine is contraindicated (see sections “Contraindications” and “Special instructions”).

Digoxin

Digoxin considered a carrier protein substrate P-glycoprotein (Pgp ). It is known that clarithromycin is capable of inhibiting Pgp . When used simultaneouslyclarithromycin and digoxin, inhibition Pgp clarithromycin may increase digoxin exposure.During post-marketing surveillance, increased serum digoxin concentrations have been reported in patients receiving Klacid.® simultaneously with digoxin. Some patients have developed signs of digitalis toxicity, including potentially fatal arrhythmias. Serum digoxin concentrations should be carefully monitored in patients receiving digoxin andKlacid® simultaneously.

Zidovudine .

Simultaneous oral administration of the drug Klacid® in tablets and zidovudine in adult HIV-infected patients may result in a decrease in the steady-state concentration of zidovudine. Due to the fact that Klacid® interferes with the absorption of concomitantly administered orally administered zidovudine, this can be largely avoided by maintaining a 4-hour interval between doses of Klacid® and zidovudine. This interaction does not occur in HIV-infected children receiving Klacid suspension® simultaneously with zidovudine or dideoxyinosine. Such an interaction is unlikely when clarithromycin is administered as an intravenous infusion.

Phenytoin and valproate .

There have been spontaneous or published reports of inhibitor interactions CYP3 A , including clarithromycin, with drugs that are not considered metabolizable CYP3 A (eg, phenytoin and valproate). When prescribing such drugs simultaneously with the drugKlacid® It is recommended to determine their level in serum. Increased serum concentrations of these drugs have been reported.

Bidirectional drug interactions

Atazanavir

Atazanavir and clarithromycin are substrates and inhibitors CYP3 A . There is evidence of a bidirectional interaction between these drugs. Concomitant use of the drug Klacid® (500 mg twice daily) with atazanavir (400 mg once daily) resulted in a two-fold increase in clarithromycin exposure, a decrease in 14- OH -clarithromycin by 70% and increase AUC atazanavir by 28%. Due to the wide therapeutic range, reduce the dose of the drugKlacid® not required in patients with normal renal function. For patients with moderate renal failure (creatinine clearance from 30 to 60 ml/min), the dose of the drugKlacid® should be reduced by 50%. For patients with creatinine clearance less than 30 ml/min, the dose of the drug Klacid® should be reduced by 75% by using the appropriate dosage form. Doses of Klacid ® higher than 1000 mg per day should not be used concomitantly with protease inhibitors.

Calcium channel blockers .

Due to the risk of developingarterial hypotension should be used with cautionKlacid® concomitantly with calcium channel blockers that are metabolized CYP3 A 4 (eg verapamil, amlodipine, diltiazem). Interaction may increase plasma concentrations of both clarithromycin and calcium channel blockers. Hypotension, bradyarrhythmia, and lactic acidosis have been observed in patients receiving clarithromycin and verapamil concomitantly.

Itraconazole

Itraconazole and clarithromycin are substrates and inhibitors CYP3 A , leading to a two-way drug interaction. Clarithromycin may increase plasma levels of itraconazole, while itraconazole may increase plasma levels of clarithromycin. When using itraconazole andKlacid® simultaneouslyPatients should be closely monitored by a physician to identify signs and symptoms of enhanced or prolonged pharmacological effects.

Saquinavir

Saquinarir and clarithromycin are substrates and inhibitors of CYP3A, and there is evidence of a bidirectional interaction between these drugs. A study in 12 healthy volunteers showed that concomitant use of Klacid® (500 mg twice daily) and saquinavir (soft gelatin capsules, 1200 mg three times daily) causes an increase in steady-state AUC and C max saquinavir by 177% and 187% compared with saquinavir alone. AUC and C max clarithromycin increased by approximately 40% compared with the values ​​observed when taking the drug Klacid® separately. There is no need to adjust doses if both drugs are used simultaneously for a limited period of time and in the doses/dosage forms studied. The results of drug interaction studies using soft gelatin capsules may not be consistent with the effects observed with saquinavir in the hard gelatin capsule form. Results from drug interaction studies using saquinavir alone may not be consistent with the effects observed with saquinavir/ritonavir. When saquinavir is used with ritonavir, the possible effects of ritonavir on clarithromycin should be considered (see Drug Interactions section).

special instructions

Use of any antimicrobial therapy, particularly clarithromycin, to treatH . pylori -infections can cause selection of resistant microorganisms.

Klacid® should not be prescribed to pregnant women without a careful assessment of the benefit/risk ratio, especially in the first three months of pregnancy.

Long-term use, as with other antibiotics, can cause excessive growth of bacteria and fungi that are insensitive to the drug. If superinfection occurs, appropriate therapy should be initiated.

The drug should be used with caution in patients with severe renal failure.

While taking clarithromycinliver dysfunction has been reported, including elevated liver enzymes,hepatocellular and/or cholestatic hepatitis, with or without jaundice. This liver dysfunction can be severe and is usually reversible. There have also been cases of fatal liver failure that have been associated with serious concomitant diseases and/or concomitant use of medications. If symptoms of hepatitis such as anorexia, jaundice, dark urine, itching or tenderness of the abdomen occur, stop using clarithromycin immediately.

Reports of pseudomembranous colitis, ranging in severity from mild to life-threatening, have been reported with the use of almost all antibacterial drugs, including macrolides. When using almost all antibacterial drugs, including Klacid® , diarrhea caused byClostridium difficile(CDAD ) and varies in severity from mild diarrhea to fatal colitis.

Taking antibacterial drugs alters the normal intestinal flora, leading to increased growthC. difficile. It is necessary to take into account the possibility of CDAD in all patients who suffer from diarrhea after taking antibiotics. It is necessary to carefully collect anamnesis, since cases of CDAD two months after taking antibacterial drugs.

Klacid ® excreted mainly by the liver. Therefore, caution should be exercised when using the drug in patients with impaired liver function, as well as in patients with moderate or severe renal impairment.

Colchicine .

In p Marketing reports have reported colchicine toxicity during concomitant use of clarithromycin and colchicine, especially in elderly patients, some of which have occurred in patients with renal impairment. Deaths have been reported in some of these patients (see section "Drug Interactions"). Concomitant use of clarithromycin and colchicine is contraindicated (see section “Contraindications”).

Should be prescribed with cautionclarithromycinconcomitantly with triazolobenzodiazepines such as triazolam and midazolam for intravenous or oromucosal administration (see section "Drug Interactions").

QT prolongation

Prolongation of myocardial repolarization and QT interval, indicating the risk of developing cardiac arrhythmia and bidirectional tachycardia (Torsades de pointes ), observed during treatment with macrolides, including clarithromycin (see section "Side effects"). Because the following situations may result in an increased risk of ventricular arrhythmias (including torsades de pointes (Torsades de pointes )), clarithromycin should be used with caution in the following groups of patients:

.Patients with coronary artery disease, severe heart failure, conduction disturbances, or clinically significant bradycardia.

.Patients with electrolyte imbalances such as hypomagnesemia. Clarithromycin should not be given to patients with hypokalemia (see Contraindications section).

.Patients who are simultaneously taking other medications, the effect of which is accompanied by a prolongation of the QT interval (see section “Drug Interactions”).

.The simultaneous administration of clarithromycin with astemizole, cisapride, pimozide and terfenadine is contraindicated (see section “Contraindications”).

.Clarithromycin should not be used in patients with congenital or established acquired prolongation of the QT interval or a history of ventricular arrhythmias (see section "Contraindications").

Pneumonia .

Due to developing resistanceStreptococcus pneumoniaeto macrolides, it is important to conduct a sensitivity test when prescribing clarithromycin for the treatment of community-acquired pneumonia. In case of hospital-acquired pneumonia clarithromycin should be used in combination with other appropriate antibiotics.

Mild to moderate skin and soft tissue infections.

The most common causative agents of such infections areStaphylococcus aureus And Streptococcus pyogenes, which may also be resistant to macrolides. Therefore, sensitivity testing is necessary. In cases where the use of beta-lactam antibiotics is not possible (for example, due to allergies), other antibiotics such as clindamycin may be the first choice. Currently, macrolides are used only to treat certain types of skin and soft tissue infections, such as those caused byCorynebacterium minutissimum, acne vulgaris and erysipelas and in situations where treatment with penicillin is impossible.

In case of severe acute hypersensitivity reactions such as anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis and drug skin reaction accompanied by eosinophilia and systemic manifestations ( DRESS ), use of the drugKlacid® should be stopped immediately and appropriate treatment initiated immediately.

Klacid® should be used with caution concomitantly with cytochrome C enzyme inducers YP3 A 4 (see section "Drug interactions").

Possible cross-resistance between clarithromycin and other macrolide drugs, as well as lincomycin and clindamycin, should also be considered.

HMG-CoA reductase inhibitors (statins) .

Simultaneous use of the drugKlacid® with lovastatin or simvastatin is contraindicated (see section “Contraindications”). Caution should be exercised when prescribing the drugKlacid® with other statins. There is information about the occurrence of rhabdomyolysis in patients who simultaneously took Klacid® and statins. Patients should be monitored for signs and symptoms of myopathy. If concomitant use of clarithromycin and statins is unavoidable, it is recommended to prescribe the minimum registered dose of the statin. A statin that is not metabolically dependent should be considered CYP3 A , for example, fluvastatin (see section "Drug interactions").

Oral hypoglycemic agents/insulin .

Klacid® and oral hypoglycemic agents (such as sulfonylureas) and/or insulin, significant hypoglycemia may occur. Close monitoring of glucose levels is recommended.

Oral anticoagulants .

When using the drug simultaneouslyKlacid® with warfarin there is a risk of serious bleeding and a significant increase in INR (international normalized ratio) and prothrombin time. When used simultaneouslyKlacida® and oral anticoagulants, it is necessary to frequently monitor the INR and prothrombin time.

Pregnancy and lactation

Pregnancy

The safety of clarithromycin during pregnancy has not been established. For this reason, the use of the drugKlacid® not recommended during pregnancy without careful benefit-risk analysis.

Lactation period

There is no data on the safety of Klacid ® during breastfeeding. Clarithromycin is excreted in breast milk.

Features of the effect of the drug on the ability to drive a vehicle and potentially dangerous mechanisms

There are no data on the effect of clarithromycin on the ability to drive vehicles and operate machinery. Before operating vehicles and machinery, you should take into account the possible occurrence of dizziness, vertigo, confusion and disorientation that may occur when using the drugKlacid® .

Overdose

Symptoms:

Existing reports indicate that gastrointestinal adverse reactions should be expected when large amounts of clarithromycin are taken orally. There is a report of one patient with a history of bipolar disorder who took 8 grams of clarithromycin and experienced altered mental status, paranoid behavior, hypokalemia, and hypoxemia.

Treatment:

Adverse reactions accompanying overdose should be treated by immediate elimination of unabsorbed drug and supportive care. As with other macrolides, hemodialysis or peritoneal dialysis is unlikely to significantly affect clarithromycin serum levels..

Incompatibility

Information is absent.

Release form and packaging

7 tablets are placed in a blister pack.

2 contour packages together with instructions for medical use in the state and Russian languages ​​are placed in a cardboard pack.

Storage conditions

Store in a place protected from light at a temperature not exceeding 30 ºС.

Keep out of the reach of children!

Shelf life

Do not take the drug after the expiration date indicated on the package.

Conditions for dispensing from pharmacies

On prescription

Manufacturer

Abbvi S.r.l., Italy

S.R. 148 Pontina K

Registration Certificate Holder

Abbott Laboratories GmbH, Hannover, Germany

Packer

Abbvi S.r.l., Italy

S.R. 148 Pontina K M 52, SNS - Campoverde di Aprilia (loc. Aprilia) - 04011 Aprilia (LT)

Address of the organization that receives claims from consumers on the quality of products (goods) in the territory of the Republic of Kazakhstan and is responsible for post-registration monitoring of the safety of the medicinal product:

Abbott Kazakhstan LLP

050059 Almaty, Republic of Kazakhstan.

Dostyk Ave. 117/6, Business Center “Khan Tengri-2”,

tel.: +7 7272447544, +7 7272447644,

e-mail: [email protected]

SOLID 1000297883 v 6 .0

Thanks to clarithromycin the drug has a bacteriological effect. 5 ml of solution contains 250 mg of active substance.

The product contains the following excipients:

• carbomer (carbopol 974P) is used as a thickener;
• Povidone K90 is designed to bind toxins;
• silicon dioxide has an absorbent effect;
• titanium dioxide gives the powder a white color;
• xanthan gum increases the viscosity of the suspension;
• fruit flavoring gives the suspension a pleasant smell so that children do not refuse to take the product;
• Potassium sorbate is intended to increase the shelf life of the drug.

pharmachologic effect

Klacid is part of the group of macrolide antibiotics. Active substance of the drug suppresses the activity of pathogenic microorganisms. In large doses, Klacid destroys harmful bacteria.

The therapeutic effect of the antibiotic is due to the fact that clarithromycin interferes with the process of protein formation in the bacterial cell.

The medicine affects the following microorganisms:

Release form

White powder is intended for preparing a suspension. When mixed with water, a suspension with a fruity aroma is formed.

There are 2 dosage forms of the drug - 125 mg and 250 mg. The 125 mg suspension can be purchased in a 60 ml bottle. For a dosage of 250 mg, a plastic container with a volume of 100 ml is intended.

Dosage of children's medicine

To prepare the solution, you need to add water to the bottle with the powder to a certain level. The container with liquid must be shaken.

The finished solution retains its healing properties for 2 weeks. After this, it is recommended to pour out the solution. If the course of treatment exceeds 2 weeks, you will have to prepare a new suspension.

The liquid should be stored at room temperature. Before each dose, the bottle should be shaken vigorously.

When calculating the dosage of Klacid suspension for children, it is necessary to take into account that per 1 kg of baby’s weight there should be up to 7.5 mg of clarithromycin. The suspension should be given to a sick child 2 times a day.

The duration of taking the drug is determined by the doctor, based on the patient's condition. It is not recommended to take the antibiotic for more than 2 weeks.

Check out the instructions for using the antibiotic on our website.

Read about the effective antiviral drug Acyclovir 200 mg tablets for children.

You can find out the advantages and disadvantages of the antibiotic Azithromycin 250 mg for children.

Indications for use

Klacid children's suspension is prescribed for the treatment of the following diseases:

The next video is a program by Dr. Komarovsky dedicated to antibiotics. When should they be prescribed, how long to take them and what side effects should be observed:

Side effects

After taking an antibiotic some children have allergic reactions. Treatment may lead to disruption of the digestive system.

The solution causes anxiety, fear and insomnia in the baby. Due to a sharp release of adrenaline, the child experiences disorientation in space.

This medicine may cause nausea, vomiting, and tinnitus.

Pathogenic microorganisms become resistant to the active component of the drug over time. You should not take the product for more than 2 weeks.

Contraindications

The antibiotic should not be used in case of hypersensitivity to the substances included in the drug. The dosage for the treatment of children with liver and kidney diseases should be reduced by 2 times.

If headache, dizziness and diarrhea occur, you should stop taking the suspension.

How does it interact with other substances?

An antibiotic can cause harm to the body in combination with the following drugs:

• Astemizole;
• Cisapride;
• Terfenadine;
• Limozide.

The ban is due to the fact that clarithromycin in combination with these drugs leads to heart rhythm disturbances. The antibiotic cannot be used together with alkaloids, as this may cause poisoning.

The medicine reduces the therapeutic effect of Rifabutin. When taken simultaneously with Ritonavir, the dosage must be adjusted.

Negative consequences may occur in patients taking Triazole. Patients may experience drowsiness.

Signs of overdose

Exceeding the dose indicated in the instructions may cause digestive upset. In this case, it is necessary to rinse the baby’s stomach.

special instructions

Long-term use of an antibiotic can cause the development of superinfection. The patient experiences the growth of pathogenic microorganisms that are insensitive to the active substance of the drug. During the course of treatment, it is necessary to monitor the level of enzymes in the blood. If signs of hepatitis appear, treatment with Klacid should be stopped.

Storage conditions and period and price in the Russian Federation

The powder retains its properties for 3 years. Means It is recommended to store at temperatures up to 30 degrees.

You can purchase a Klacid suspension for children containing 125 mg of active ingredient for an average price of 370 rubles. To purchase a bottle containing 250 mg of clarithromycin, you need to pay about 460 rubles.

Klacid is an antibiotic from the macrolide group, which has a detrimental effect on a wide range of pathogenic and opportunistic microorganisms.

The drug is used to treat infectious and inflammatory diseases of various organs and systems caused by antibiotic-sensitive microbes.

In this article we will look at why doctors prescribe Klacid, including instructions for use, analogues and prices for this drug in pharmacies. Real REVIEWS of people who have already used Klacid can be read in the comments.

Composition and release form

Today Klacid is available in four different dosage forms:

• Powder for making a suspension (sometimes mistakenly called syrup) for children. Note that this form has two dosages: 125 mg and 250 mg in 5 ml of the finished medicine. To hide the bitterness inherent in antibacterial drugs, sucrose and fruit flavoring were added to the suspension.
• Tablets, dose 250 and 500 mg, film-coated. The latter hides the unpleasant, bitter taste of Klacid (characteristic of all antibiotics without exception). The instructions for use indicate that the Klacida shell is yellow.
  powder from which a solution for infusion (intravenous drip) is prepared.

Pharmacological action: the active substance clarithromycin belongs to the group of macrolides, semisynthetic antibiotics.

Indications for use

The instructions for Klacid state that this drug should be used to treat the following diseases:

1. Infectious diseases of the respiratory tract;
2. Infectious diseases of the ENT organs;
3. Infectious diseases of the skin and soft tissues;
4. Various infectious diseases caused by mycobacteria;
5. Destruction of bacteria that cause ulceration of the stomach and duodenum;
6. Prevention of infectious diseases caused by mycobacteria in patients suffering from AIDS;
7. Purulent infectious processes of various localizations.

pharmachologic effect

Klacid is a semi-synthetic antibiotic from the macrolide group. Under the influence of the main active ingredient of the drug, clarithromycin, the ability of pathogenic microorganisms to reproduce is suppressed by blocking bacterial protein synthesis.

The drug is highly effective against gram-positive and gram-negative flora, anaerobes, and some pathogens of sexually transmitted infections. Enterobacteriaceae and Pseudomonas aeruginosa show resistance to the active component of the drug.

When taking the tablet orally, the active substance of the drug is evenly distributed in the tissues of internal organs and biological fluids.

Instructions for use

According to the instructions for use, Klacid 250 and Klacid 500 mg tablets are intended for use by adults and adolescents over 12 years of age, provided that their body weight is at least 40 kg. If a teenager has already reached the age of 12 years, but his body weight is below 40 kg, then he should be given Klacid in the form of a suspension.

The tablets are taken orally, regardless of food, at any convenient time, swallowing them whole, without biting, chewing or crushing in other ways, but with clean still water.

• Children over 12 years of age and adults are prescribed 1 tablet of 250 mg 2 times a day. In severe cases, the single dose is increased to 500 mg. As a rule, the course of treatment is 5-14 days, with the exception of sinusitis and community-acquired pneumonia - it takes at least 6 days to cure them.
• For mycobacterial infections, except tuberculosis, the drug is taken 1 tablet of 500 mg 2 times a day.
• For the prevention of infections caused by MAS, the dose is also 500 mg 2 times a day.
• Treatment of odontogenic infections is carried out with clarithromycin in a daily dose of 500 mg - 250 mg 2 times a day. Course – 5 days.

If the infection turns out to be severe and cannot be treated, then you should switch to intravenous administration of Klacid. After improvements appear, intravenous administration of the drug is stopped and again switched to taking it in the form of tablets or suspension.

Contraindications

Contraindications to the use of all dosage forms of Klacida:

1. Breastfeeding period;
2. Hypokalemia (risk of QT prolongation);
3. Severe liver failure due to renal failure;
4. Hypersensitivity to the components of the drug and other macrolides;
5. A history of ventricular arrhythmia or ventricular tachycardia of the “pirouette” type, prolongation of the QT interval;
6. A history of cholestatic hepatitis or jaundice that developed during the use of clarithromycin;
7. Concomitant use with cisapride, pimozide, astemizole, terfenadine; ergotamine, dihydroergotamine and other ergot alkaloids; midazolam for oral administration; colchicine;
8. Combination with HMG-CoA reductase inhibitors (statins), which are mainly metabolized by the CYP3A4 isoenzyme (simvastatin, lovastatin), due to the high risk of developing myopathy and rhabdomyolysis.

The drug is prescribed orally with caution in the following cases:

1. Moderate to severe renal/liver failure;
2. Coronary heart disease, severe bradycardia (less than 50 beats per minute), hypomagnesemia, severe heart failure;
3. Pregnancy;
4. Myasthenia gravis;
5. Diabetes mellitus (for suspension, because it contains sucrose).

If intravenous administration is necessary, the drug is prescribed with caution to patients with moderate and severe renal failure.

Side effects

More common side effects:

• Indicators: increased activity of liver enzymes.
• From the central nervous system: migraines, changes in taste.
• An inflammatory process may appear on the skin after injection and pain at the injection site during palpation.
• Gastrointestinal tract: loose stools, indigestion, nausea and vomiting, stomach pain.

Less common may occur: spread of candida fungus in the mouth, leukopenia, anaphylactic shock, thrombocytopenia, sleep disturbance, muscle pain, inflammation of the pancreas, increased creatinine, low blood sugar, convulsive reactions, temporary hearing loss, liver disease, uneven heartbeat, skin rash, urticaria.

Analogues of Klacid

Structural analogues of the active substance:

• Arvicin;
• Arvicin retard;
• Binoculars;
• Zimbaktar;
• Kispar;
• Clubax;
• Clarbuckt;
• Clarithromycin;
• Clarithrosin;
• Claricin;
• Claricite;
• Claromine;
• Klasine;
• Klacid SR;
• Clerimed;
• Coater;
• Crixan;
• Seydon-Sanovel;
• CP-Klaren;
• Fromilid;
• Fromilid Uno;
• Ecositrin.

Attention: the use of analogues must be agreed with the attending physician.

Prices

The average price of Klacid SR 500 mg tablets in pharmacies (Moscow) is 500 rubles. Klacid powder for oral administration 125 mg/5 ml 60 ml – 380 rub.

Klacid is a broad-spectrum antibiotic used to treat infectious diseases of the respiratory tract and soft tissues.

pharmachologic effect

Klacid belongs to the group of macrolide antibiotics that have an antibacterial effect.

The drug is effective against pneumococcus, Staphylococcus aureus, viridans streptococcus, listeriosis pathogens, group A, B, C, F, G streptococci, Haemophilus influenzae infection, pneumonia, pneumochlamydia, sporotrichosis, peptococcus, chlamydia, gonorrhea, leprosy, erysipelas, as well as Legionnaires' disease and pneumonia of mycoplasma etiology. Klacid has a positive effect on the pathogens of whooping cough, avian pasteurellosis, human toxic infections, acne, borelliosis, syphilis, and enterocolitis.

Klacid is not effective in treating enterobacteriaceae, Pseudomonas aeruginosa and all other gram-negative bacteria that do not degrade lactose.

The active substance, clarithromocin, is released during its passage throughout the gastrointestinal tract due to the fact that the tablets are a crystalline homogeneous mass.

Release form

Klacid is produced in the form:

• Yellow oval film-coated tablets of 250 mg and 500 mg (Klacid 500 or Klacid SR), containing 250 mg and 500 mg of the active substance clarithromycin, respectively. Excipients: quinoline yellow, croscarmellose sodium, pregelatinized starch, microcrystalline cellulose, stearic acid, silicon dioxide, talc, magnesium stearate, povidone. 7-42 tablets per package;
• White granulated powder with a fruity aroma for the preparation of suspensions, which, when added with water, forms an opaque suspension of Klacid. 5 ml contains 125 mg or 250 mg of active ingredient. In dark plastic bottles of 60 ml and 100 ml, respectively, with a dosing syringe or spoon. Excipients - povidone K90, carbomer, castor oil, hypromellose phthalate, maltodextrin, silicon dioxide, sucrose, xanthan gum, potassium sorbate, titanium dioxide, anhydrous citric acid, fruit flavoring.

Indications for use of Klacida

According to the instructions, Klacid is used for:

• Common mycobacterial infections that cause Mycobacterium intracellulare and Mycobacterium avium;
• Otitis;
• Infections of the lower respiratory tract - bronchitis, pneumonia;
• Infections of the skin and soft tissues – folliculitis, cellulite, erysipelas;
• Infections of the upper respiratory tract – polysinusitis, pharyngitis, monosinusitis;
• Localized mycobacterial infections caused by Mycobacterium fortuitum, Mycobacterium chelonae and Mycobacterium kansasii;
• Eradication of Helicobacter pylori and reduction in the frequency of relapses of duodenal ulcers;
• Prevention of the spread of infection caused by Mycobacterium avium complex (MAC);
• Odontogenic infections.

Contraindications

According to the instructions, Klacid is contraindicated for:

• Severe liver dysfunction;
• Severe renal dysfunction;
• Porphyria;
• Concomitant use with pimozide, cisapride, dihydroergotamine, astemizole, terfenadine, ergotamine;
• Pregnancy, during lactation;
• Hypersensitivity to macrolide antibiotics.

According to the instructions, Klacid is not prescribed to children under 3 years of age in tablet form.

Instructions for use Klacida

Typically, the drug is taken 1 tablet of Klacida 500 per day, regardless of food. In severe cases, the dose can be doubled. Klacida tablets should not be broken or chewed. The duration of treatment is usually from 6 days to two weeks.

Depending on the disease, Klacid is used:

• For mycobacterial infection - 1 tablet Klacid 500 twice a day;
• When treating odontogenic infections - 250 mg of the drug 2 times a day for 5 days;
• For the prevention of MAC infections - 1 tablet of Klacida SR twice a day;
• To destroy H. pylori bacteria in duodenal ulcers for 7–14 days - 1 tablet of Klacida 500 2 times a day, combined with lansoprazole and amoxicillin, or for 7 days - 1 tablet of Klacida SR twice a day simultaneously with lansoprazole and metronidazole .

Side effects

Although, according to reviews, Klacid is usually well tolerated, while taking the drug, abdominal pain, ventricular arrhythmia, accompanied by ventricular tachycardia, nausea, pancreatitis, diarrhea, vomiting, discoloration of the tongue and teeth, stomatitis, stomach pain, oral candidiasis, inflammation may occur. tongue, pseudomembranous colitis.

Deterioration of liver function and hepatic cell hepatitis with jaundice are rare and reversible.

Also, according to reviews of Klacida, dizziness, transient headaches, anxiety and nightmares, insomnia, ringing in the ears, depersonalization, hallucinations and psychosis, convulsions, fear, and confusion may appear. According to reviews of Klacida, these effects develop much less frequently if treatment is carried out in a calm environment.

In some cases, when using Klacid, skin itching, urticaria, anaphylaxis, skin hyperemia, and Stevens-Johnson syndrome are observed.

When using Klacid simultaneously with other drugs, caution should be exercised.

Storage conditions

Klacid is classified as a Schedule B drug and is available with a prescription. Shelf life – 3 years.

Sincerely,

Description of the dosage form

Release form, composition and packaging

Film-coated tablets yellow, oval.

Excipients: croscarmellose sodium, microcrystalline cellulose, pregelatinized starch, silicon dioxide, povidone, stearic acid, magnesium stearate, talc, quinoline yellow (E104).

Shell composition: hypromellose, hyprolose, propylene glycol, sorbitan monooleate, titanium dioxide, sorbic acid, vanillin, quinoline yellow (E104).

Film-coated tablets light yellow, oval.

Excipients: croscarmellose, microcrystalline cellulose, silicon dioxide, povidone, stearic acid, magnesium stearate, talc.

Shell composition: hypromellose, hydroxypropylcellulose, propylene glycol, sorbitan monooleate, titanium dioxide, sorbic acid, vanillin, quinoline yellow (E104).

7 pcs. - blisters (1) - cardboard packs.
7 pcs. - blisters (2) - cardboard packs.
7 pcs. - blisters (3) - cardboard packs.
10 pieces. - blisters (1) - cardboard packs.
10 pieces. - blisters (2) - cardboard packs.
10 pieces. - blisters (3) - cardboard packs.
14 pcs. - blisters (1) - cardboard packs.
14 pcs. - blisters (2) - cardboard packs.
14 pcs. - blisters (3) - cardboard packs.

Powder white or almost white, granular, with a fruity aroma; when water is added, a white or almost white opaque suspension with a fruity aroma is formed.

Excipients: carbomer (carbopol 974P), povidone K90, hypromellose phthalate, castor oil, silicon dioxide, maltodextrin, sucrose, titanium dioxide, xanthan gum, fruit flavor, potassium sorbate, anhydrous citric acid.

42.3 g - plastic bottles with a volume of 60 ml (1) complete with a dosing spoon or syringe - cardboard packs.

Powder for the preparation of a suspension for oral administration in the form of granules of white or almost white color, with a fruity aroma; when water is added, a white or almost white opaque suspension with a fruity aroma is formed.

Excipients: carbomer (carbopol 974P), povidone K90, hypromellose phthalate, castor oil, silicon dioxide, maltodextrin, sucrose, titanium dioxide, xanthan gum, fruit flavor, potassium sorbate, anhydrous citric acid.

70.7 g - plastic bottles with a volume of 100 ml (1) complete with a dosing spoon or syringe - cardboard packs.

Clinical and pharmacological group

Macrolide antibiotic

pharmachologic effect

Semi-synthetic antibiotic of the macrolide group. It has an antibacterial effect by interacting with the 50S ribosomal subunit of bacteria and inhibiting protein synthesis in the microbial cell.

Clarithromycin has demonstrated high in vitro activity against standard and isolated bacterial cultures. Highly effective against many aerobic and anaerobic gram-positive and gram-negative microorganisms. In vitro studies confirm high efficiency clarithromycin against Legionella pneumophila, Mycoplasma pneumoniae and Helicobacter (Campylobacter) pylori.

The drug is also active against aerobic gram-positive microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes; aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainftuenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Legionella pneumophila; others 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.

To clarithromycin insensitive Enterobacteriaceae, Pseudomonas spp., as well as other non-lactose-degrading gram-negative bacteria.

The production of β-lactamases does not affect the activity of clarithromycin. Most strains of staphylococci resistant to methicillin and oxacillin are also resistant to clarithromycin.

The sensitivity of Helicobacter pylori to clarithromycin was studied on Helicobacter pylori isolates isolated from 104 patients before starting drug therapy. In 4 patients, clarithromycin-resistant Helicobacter pylori strains were isolated, in 2 patients, intermediate-resistant strains were isolated, and in the remaining 98 patients, Helicobacter pylori isolates were sensitive to clarithromycin.

Clarithromycin is effective in vitro and against most strains of the following microorganisms (however, the safety and effectiveness of the use of clarithromycin in clinical practice has not been confirmed by clinical studies and the practical significance remains unclear): aerobic gram-positive microorganisms: Streptococcus agalactiae, streptococci (groups C, F, G), streptococci of the Viridans group; aerobic gram-negative microorganisms: Bordetella pertussis, Pasteurella multocida; anaerobic gram-positive microorganisms:Сlostridium perfringens, Peptococcus niger, Propionibacterium acnes; anaerobic gram-negative microorganisms: Bacteroides melaninogenicus; Borrelia burgdorferi, Treponema pallidum, 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 parent substance, or 1-2 times weaker against most microorganisms. The exception is Haemophilus influenzae, for which the effectiveness of the metabolite is 2 times higher. The parent substance and its main metabolite have either an additive or synergistic effect against Haemophilus influenzae in vitro and in vivo, depending on the bacterial culture.

Sensitivity studies

Quantitative methods that require measuring the diameter of the growth inhibition zone of microorganisms provide the most accurate estimates of the sensitivity of bacteria to antimicrobial agents. One recommended susceptibility testing procedure uses discs soaked in 15 μg of clarithromycin (Kirby-Bauer diffusion test); the test results are interpreted depending on the diameter of the zone of growth inhibition of the microorganism and the value of the minimum inhibitory concentration (MIC) of clarithromycin. The MIC value is determined by diluting the medium or diffusion into agar. Laboratory tests give one of three results: 1) "resistant" - it can be considered that the infection cannot be treated with this drug; 2) "moderately sensitive" - ​​the therapeutic effect is ambiguous, and it is possible that increasing the dosage may lead to sensitivity; 3) "sensitive" - ​​the infection can be considered to be treatable with clarithromycin.

Pharmacokinetics

The first data on pharmacokinetics were obtained from the study of clarithromycin tablets.

The bioavailability and pharmacokinetics of clarithromycin suspension were studied in healthy adults and children.

Healthy

Suction and distribution

With a single dose in adults, the bioavailability of the suspension was equivalent to the bioavailability of tablets (at the same doses) or slightly higher. Eating slightly delayed the absorption of clarithromycin suspension, but did not affect the overall bioavailability of the drug.

When taking the pediatric suspension (after meals), the Cmax and AUC of clarithromycin were 0.95 µg/ml, 6.5 µg×h/ml, respectively.

When clarithromycin suspension was administered at a dose of 250 mg every 12 hours in adults, steady-state blood levels were practically achieved by the fifth dose. The pharmacokinetic parameters were as follows: Cmax 1.98 µg/ml, AUC 11.5 µg×h/ml and Tmax 2.8 h for clarithromycin and, respectively, 0.67, 5.33, 2.9 for 14-hydroxyclarithromycin.

In healthy subjects, serum concentrations peaked within 2 hours after oral administration. C ss max of 14-hydroxyclarithromycin is about 0.6 μg/ml. When clarithromycin is prescribed at a dose of 500 mg every 12 hours, the C ss max of 14-hydroxyclarithromycin is slightly higher (up to 1 μg/ml). When using both doses, C ss max metabolite is usually achieved within 2-3 days.

In in vitro studies, the binding of clarithromycin to plasma proteins averaged about 70% at clinically relevant concentrations from 0.45 to 4.5 μg/ml.

Metabolism and excretion

Clarithromycin is metabolized in the liver under the action of the CYP3A isoenzyme to form the microbiologically active metabolite 14-hydroxyclarithromycin.

T1/2 of clarithromycin when taking a children's suspension (after meals) was 3.7 hours. When using a clarithromycin suspension at a dose of 250 mg every 12 hours in adults, T1/2 was 3.2 hours for clarithromycin and 4.9 for 14-hydroxyclarithromycin.

In healthy people when using clarithromycin: at a dose of 250 mg every 12 hours T1/2 of 14-hydroxyclarithromycin is 12 hours; at a dose of 500 mg every 12 hours T1/2 of 14-hydroxyclarithromycin is about 7 hours.

When clarithromycin is used at a dose of 250 mg every 12 hours, approximately 20% of the dose is excreted unchanged in the urine. When clarithromycin is used at a dose of 500 mg every 12 hours, approximately 30% of the dose is excreted unchanged in the urine. The renal clearance of clarithromycin is not significantly dose-dependent and approaches the normal glomerular filtration rate. The main metabolite found in urine is 14-hydroxyclarithromycin, which accounts for 10-15% of the dose (250 mg or 500 mg every 12 hours).

Sick

Clarithromycin and its metabolite are well distributed in tissues and body fluids. Tissue concentrations are usually several times higher than serum concentrations.

Examples of tissue and serum concentrations after oral administration of the drug at a dose of 250 mg every 12 hours are given in the table:

U children who require oral antibiotic treatment, clarithromycin is characterized by high bioavailability. Moreover, its pharmacokinetic profile was similar to that of adults taking the same suspension. The drug is quickly and well absorbed from the gastrointestinal tract. Food slightly delays the absorption of clarithromycin without significantly affecting its bioavailability or pharmacokinetic properties.

The equilibrium parameters of the pharmacokinetics of clarithromycin, achieved after 5 days (dose 9) were as follows: Cmax - 4.6 μg/ml, AUC - 15.7 μg×h/ml and Tmax - 2.8 h; the corresponding values ​​for 14-hydroxyclarithromycin were 1.64 μg/ml, 6.69 μg×h/ml and 2.7 h, respectively. The calculated T1/2 of clarithromycin and its metabolite are 2.2 and 4.3 hours, respectively.

Pharmacokinetics in special clinical situations

In elderly patients receiving clarithromycin repeated at a dose of 500 mg, a comparative study revealed increased plasma levels of the drug and slower elimination compared with those in young healthy people. However, there was no difference between the two groups when adjustment was made for creatinine clearance. Changes in the pharmacokinetics of clarithromycin reflect renal function and not the age of the patient.

In patients with otitis media, 2.5 hours after taking the fifth dose (7.5 mg/kg 2 times/day), the average concentrations of clarithromycin and 14-hydroxyclarithromycin in the middle ear were 2.53 and 1.27 mcg/g. Concentrations of the drug and its metabolite were 2 times higher than their serum levels.

In patients with impaired liver function, C ss of clarithromycin did not differ from those in healthy people, while the level of the metabolite was lower. The decrease in the formation of 14-hydroxyclarithromycin was partially offset by an increase in the renal clearance of clarithromycin compared with that in healthy subjects.

In patients with impaired renal function who received the drug orally at a dose of 500 mg repeatedly, plasma levels, T1/2, Cmax, Cmin and AUC of clarithromycin and the metabolite were higher than in healthy people. Deviations in these parameters correlated with the degree of renal failure: with more severe renal dysfunction, the differences were more significant.

In adult patients with HIV infection receiving the drug in usual doses, C ss of clarithromycin and its metabolite were similar to those in healthy people. However, when clarithromycin is used in higher doses, which may be required in the treatment of mycobacterial infections, antibiotic concentrations may be significantly higher than usual.

In children with HIV infection taking clarithromycin at a dose of 15-30 mg/kg/day in 2 divided doses, steady-state Cmax values ​​usually ranged from 8 to 20 mcg/ml. However, in children with HIV infection who received a clarithromycin suspension at a dose of 30 mcg/kg/day in 2 doses, C max reached 23 mcg/ml. When using the drug in higher doses, a prolongation of T1/2 was observed compared with that in healthy people receiving clarithromycin in usual doses. The increase in plasma concentration and T1/2 duration when clarithromycin is prescribed in higher doses is consistent with the known nonlinearity of the pharmacokinetics of the drug.

Indications for use of the drug

- lower respiratory tract infections (bronchitis, pneumonia);

- upper respiratory tract infections (pharyngitis, sinusitis);

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

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

- localized mycobacterial infections caused by Mycobacterium chelonae, Mycobacterium fortuitum and Mycobacterium kansasii;

— eradication of Helicobacter pylori and reduction in the frequency of relapses of duodenal ulcers;

- prevention of the spread of infection caused by the Mycobacterium avium complex (MAC) in HIV-infected patients with a content of CD4 lymphocytes (T-helper lymphocytes) of no more than 100 per 1 mm 3;

- odontogenic infections.

Dosage regimen

Pills

The drug is taken orally regardless of food intake.

Usually adults Prescribe 250 mg 2 times/day. IN more severe cases the dose is increased to 500 mg 2 times/day. Usually the duration of treatment is from 5-6 to 14 days.

Patients with CC less than 30 ml/min Prescribe half the usual dose of clarithromycin, i.e. 250 mg 1 time/day or, if more severe infections- 250 mg 2 times/day. Treatment of such patients continues for no more than 14 days.

At mycobacterial infections Prescribe 500 mg 2 times/day.

At common infections caused by MAC in patients with AIDS Treatment should be continued as long as there is clinical and microbiological evidence of its benefit. Clarithromycin should be prescribed in combination with other antimicrobial drugs.

At infectious diseases caused by mycobacteria, except tuberculosis, The duration of treatment is determined by the doctor.

For prevention of infections caused by MAC, recommended dose of clarithromycin for adults- 500 mg 2 times/day.

At odontogenic infections The dose of clarithromycin is 250 mg 2 times a day for 5 days.

For eradication of Helicobacter pylori

Combination treatment with three drugs

— clarithromycin 500 mg 2 times/day + lansoprazole 30 mg 2 times/day + amoxicillin 1000 mg 2 times/day for 10 days;

— clarithromycin 500 mg 2 times/day + omeprazole 20 mg/day + amoxicillin 1000 mg 2 times/day for 7-10 days.

Combination treatment with two drugs

— clarithromycin 500 mg 3 times/day + omeprazole 40 mg/day for 14 days with the prescription of omeprazole at a dose of 20-40 mg/day over the next 14 days;

— clarithromycin 500 mg 3 times/day + lansoprazole 60 mg/day for 14 days. For complete healing of the ulcer, additional reduction in the acidity of gastric juice may be required.

Powder for suspension for oral administration

The prepared suspension should be taken orally regardless of food intake (with milk).

To prepare the suspension, water is gradually added to the bottle with granules up to the mark, then the bottle is shaken. The prepared suspension can be stored for 14 days at room temperature.

Suspension 60 ml: 5 ml - 125 mg of clarithromycin; suspension 100 ml: 5 ml - 250 mg of clarithromycin.

Recommended daily dose of clarithromycin suspension for non-mycobacterial infections at children is 7.5 mg/kg 2 times/day. The maximum dose is 500 mg 2 times/day. The usual duration of treatment is 5-7 days, depending on the pathogen and the severity of the patient's condition. Before each use, shake the bottle of the drug well.

Recommended doses of the drug in children, taking into account body weight
Body mass* (kg)	Doses are indicated in standard teaspoons (5 ml) 2 times / day
125 mg/5 ml	250 mg/5 ml
8-11	0.5	-
12-19	1	0.5
20-29	1.5	0.75
30-40	2	1
*in children with body weight<8 кг дозу подбирают по массе тела (примерно 7.5 мг/кг 2 раза/сут)

U children with CC<30 мл/мин the dose of clarithromycin should be halved: to 250 mg 1 time / day or 250 mg 2 times / day for more severe infections. In such cases, the course of treatment should not exceed 14 days.

U children With disseminated or local mycobacterial infections The recommended dose of clarithromycin is 15-30 mg/kg/day in 2 divided doses. Treatment with clarithromycin should be continued as long as the clinical effect persists. The addition of other antimycobacterial drugs may be useful.

Recommended doses of Klacid 250 mg/5 ml in children with AIDS, taking into account body weight
Body mass* (kg)	Doses are given in standard teaspoons (5 ml)
15 mg/kg	30 mg/kg
8-11	0.5	1
12-19	1	2
20-29	1.5	3
30-40	2	4
*in children with body weight<8 кг дозу подбирают по массе тела (15-30 мг/кг/сут)

Side effect

The most common adverse events occurred from the digestive system: diarrhea, vomiting, abdominal pain, nausea. Pseudomembranous enterocolitis has been observed extremely rarely. Other adverse reactions included headache, taste disturbances, and transient increases in liver enzymes. As with the use of other macrolide antibiotics, the development of microbial resistance may occur.

Klacid suspension is comparable in safety to Klacid 250 mg tablets in adults.

Post-marketing experience

From the digestive system: glossitis, stomatitis, oral thrush, tongue discoloration, tooth discoloration (these changes are usually reversible and can be corrected by a dentist); uncommon - impaired liver function, increased activity of liver enzymes, hepatocellular and/or cholestatic hepatitis with/without jaundice; rarely - pancreatitis. Liver dysfunction can be severe but is usually reversible. In very rare cases, deaths from liver failure have been reported, which usually occur in the presence of serious concomitant diseases and/or concomitant use of other drugs.

From the central nervous system and peripheral nervous system: dizziness, anxiety, insomnia, nightmares, tinnitus, confusion, disorientation, hallucinations, psychosis, depersonalization. Side effects are temporary; a cause-and-effect relationship with the use of the drug has not been established. Rare cases of seizures have been described.

From the cardiovascular system: rarely - prolongation of the QT interval, ventricular tachycardia, ventricular tachycardia of the "pirouette" type.

From the senses: hearing loss (after cessation of treatment, hearing was usually restored), impaired sense of smell, usually combined with a perversion of taste.

From the hematopoietic system: isolated cases of leukopenia, thrombocytopenia.

From the side of metabolism: rarely - cases of hypoglycemia, some of which were observed in patients receiving oral hypoglycemic agents or insulin; isolated cases of increased serum creatinine levels (no connection with the use of clarithromycin has been established).

Allergic reactions: urticaria, rash, anaphylaxis, Stevens-Johnson syndrome, Lyell's syndrome.

Other: cases of interstitial nephritis and colchicine toxicity when used concomitantly with clarithromycin (especially in the elderly). Some of them were observed in patients with renal failure; Several deaths have been reported in similar patients.

Children with suppressed immune systems

In patients with acquired immunodeficiency syndrome and other immunodeficiency conditions receiving clarithromycin in higher doses over a long period of time for the treatment of mycobacterial infections, it is often difficult to differentiate the adverse effects of the drug from symptoms of HIV infection or intercurrent illnesses.

The main adverse events in patients taking oral clarithromycin at a dose of 1 g were nausea, vomiting, taste disturbance, abdominal pain, diarrhea, rash, abdominal bloating, headache, hearing loss, constipation, increased AST and ALT levels. Dyspnea, insomnia, and dry mouth were also reported less frequently.

In this group of patients with suppressed immunity, significant deviations of laboratory parameters from normative values ​​in specific tests (sharp increase or decrease) were recorded. Based on this, approximately 2-3% of patients taking clarithromycin orally at a dose of 1 g/day had significant laboratory abnormalities, such as increased levels of AST, ALT and decreased white blood cell and platelet counts. Fewer patients also experienced elevated blood urea nitrogen levels.

In a limited number of pediatric patients with AIDS, clarithromycin suspension has been used to treat mycobacterial infections. The main adverse events not related to the underlying disease were tinnitus, deafness, vomiting, nausea, abdominal pain, purpura, pancreatitis and increased amylase activity. In this study, significant deviations of laboratory parameters from normative values ​​(sharp increase or decrease) were recorded. Based on these criteria, one child with AIDS who received clarithromycin at a dose of<15 мг/кг/сут, отмечено значительное повышение уровня общего билирубина; среди пациентов, принимавших кларитромицин в дозе 15-25 мг/кг/сут, было зарегистрировано по одному случаю значительного повышения уровней АЛТ, остаточного азота мочевины и снижения числа тромбоцитов. У пациентов, получавших кларитромицин в максимальной дозе (≥25 мг/кг/сут), значительных изменений указанных лабораторных параметров не выявлено.

Contraindications to the use of the drug

- severe liver dysfunction;

- severe renal dysfunction (KR)<30 мл/мин);

- porphyria;

- simultaneous use with astemizole, cisapride, pimozide, terfenadine, ergotamine, dihydroergotamine;

- pregnancy;

- lactation period (breastfeeding);

- children under 3 years of age (for the dosage form in the form of tablets);

- increased sensitivity to macrolide antibiotics.

WITH caution The drug should be prescribed to patients with impaired liver and kidney function.

Use of the drug during pregnancy and lactation

The safety of clarithromycin during pregnancy and lactation has not been studied.

Clarithromycin is known to be excreted in breast milk.

Therefore, Klacid ® should be used during pregnancy and lactation only in cases where there is no safer alternative, and the risk associated with the disease itself outweighs the possible harm to the mother and fetus.

Use for liver dysfunction

The use of the drug is contraindicated in severe liver dysfunction and porphyria.

WITH caution the drug should be prescribed to patients with impaired liver function.

Use for renal impairment

The use of the drug is contraindicated in severe renal impairment (KR<30 мл/мин).

WITH caution The drug should be prescribed to patients with impaired renal function.

special instructions

Clarithromycin is eliminated primarily by the liver. In this regard, caution should be exercised when prescribing Klacid to patients with impaired liver function.

In the presence of chronic liver diseases, it is necessary to regularly monitor serum enzymes.

Caution should be exercised when treating patients with moderate to severe renal failure with clarithromycin.

In clinical practice, cases of toxicity of colchicine when combined with clarithromycin have been described, especially in elderly people. Some of them were observed in patients with renal failure; Several deaths have been reported in similar patients.

The possibility of cross-resistance between clarithromycin and other macrolide drugs, as well as lincomycin and clindamycin, must be considered.

Prescribe with caution against drugs metabolized by the liver.

In case of co-administration with warfarin or other indirect anticoagulants, it is necessary to monitor the prothrombin time.

Overdose

Taking a large dose of clarithromycin causes gastrointestinal symptoms. In one patient with a history of bipolar disorder, changes in mental status, paranoid behavior, hypokalemia, and hypoxemia were described after taking 8 g of clarithromycin.

Treatment: the unabsorbed drug should be removed from the gastrointestinal tract and symptomatic therapy should be carried out. Hemodialysis and peritoneal dialysis do not have a significant effect on the level of clarithromycin in the serum, which is also typical for other macrolide drugs.

Drug interactions

Clarithromycin is metabolized in the liver under the action of the CYP3A isoenzyme. This mechanism determines many interactions with other drugs. Clarithromycin may inhibit the biotransformation of other drugs by this system, which may result in increased serum levels.

Metabolized by the same isoenzyme CYP3A: alprazolam, astemizole, carbamazepine, cilostazol, cisapride, cyclosporine, disopyramide, ergotamine alkaloids, lovastatin, methylprednisolone, midazolam, omeprazole, oral anticoagulants (warfarin), pimozide, quinidine, rifabutin, sildena fil, simvastatin, tacrolimus , terfenadine, triazolam and vinblastine. Similar mechanisms of interaction, which are mediated by other isoenzymes of the cytochrome P450 system, are characteristic of phenytoin, theophylline and valproic acid.

In clinical studies, when theophylline or cabramazepine was combined with clarithromycin, there was a small but statistically significant (p)<0.05) повышение уровней теофиллина и карбамазепина в сыворотке крови.

In clinical practice, the following cases of interaction mediated by the CYP3A isoenzyme have been reported with the use of erythromycin and/or clarithromycin:

When clarithromycin was used simultaneously with HMG-CoA reductase inhibitors (lovastatin, simvastatin), rhabdomyolysis developed in rare cases.

With simultaneous use of clarithromycin with cisapride, an increase in the levels of the latter was observed. This may lead to prolongation of the QT interval and the development of cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsade de pointes (TdP). Similar effects have been reported in patients receiving clarithromycin with pimozide.

Macrolides cause disruption of the metabolism of terfenadine, which leads to an increase in its plasma levels and is sometimes associated with the development of arrhythmias, incl. prolongation of the QT interval, ventricular tachycardia, ventricular fibrillation and torsade de pointes (TdP). In one study of 14 healthy volunteers, the combined use of clarithromycin tablets and terfenadine resulted in a 2- to 3-fold increase in serum levels of the acid metabolite terfenadine and a prolongation of the QT interval, which was not associated with any clinical effects.

In clinical practice, cases of ventricular tachycardia of the “pirouette” type have been reported when clarithromycin is combined with quinidine or disopyramide. Serum levels of these drugs should be monitored during treatment with clarithromycin.

In clinical practice, when clarithromycin was combined with ergotamine or dihydroergotamine, cases of acute toxicity of the latter, which is characterized by vasospasm, ischemia of the limbs and other tissues, including the central nervous system, were recorded.

In patients receiving clarithromycin tablets in combination with digoxin, an increase in serum concentrations of the latter was observed. Monitoring serum digoxin levels is advisable.

Colchicine is a substrate for CYP3A and P-glycoprotein. Clarithromycin and other macrolides are inhibitors of CYP3A and P-glycoprotein. With simultaneous administration of colchicine and clarithromycin, inhibition of P-glycoprotein"