Klacid powder - instructions for use. Klacid powder - instructions for use Therapeutic effect of Klacid

Instructions for use Klacid
Buy Klacid por for Prig. suspensions for oral administration 125 mg/5 ml 42.3 g
Dosage forms
powder for the preparation of suspension for oral administration 125mg/5ml
Manufacturers
Abbott S.R.L. (Italy)
Group
Antibiotics - macrolides and azalides
Compound
The active substance is Clarithromycin.
International nonproprietary name
Clarithromycin
Synonyms
Arvicin, Binoklar, Clubax, Clubax OD, Clarbact, Clarithromycin, Clarithromycin Protech, Clarithromycin SR, Clarithromycin-OBL, Clarithromycin-Verte, Clarithromycin-Teva, Clarithrosin, Claricin, Claromin, Klacid SR, Clerimed, Fromilid, Fromilid Uno, Ecositrin
pharmachologic effect
Antibacterial (bacteriostatic), antiulcer. When taken orally, it is quickly and fairly completely absorbed. Food slows absorption without significantly affecting bioavailability. In plasma it binds to serum proteins. It is immediately oxidized in the liver to form the main metabolite 14-hydroxyclarithromycin (has pronounced antimicrobial activity against Haemophilus influenzae). Penetrates well into body fluids and tissues, creating concentrations 10 times higher than the level in blood serum. It is excreted in the urine in unchanged form and in the form of metabolites. Active against intracellular microorganisms (Mycoplasma Pneumoniae, Legionella pneumophila, Chlamydia trachomatis and Chlamydia pneumoniae, ureaplasma urealyticum), gram -positive (Streptoosoccus spp. Aphylococcus spp., Listeria monocytogenes, Corynebacterium spp.) And gram -negative bacteria (Haemophilus influenzae and haemophilus ducreyi, moraxella catarrhalis, Bordetella pertussis, Neisseria meningitidis, Borrelia burgdorferi, Pasteurella multocida, Campylobacter spp., Helicobacter pylori), some anaerobes (Eubacterium spp., Peptococcus spp., Propionibacterium spp., Clostridium perfringens, Bacteroides melaninogenicus), Toxoplasma gondii and all mycobacteria except V. tuberculosis.
Indications for use
Infections of the upper respiratory tract and ENT organs (tonsillopharyngitis, otitis media, acute sinusitis), lower respiratory tract (acute bronchitis, exacerbation of chronic bronchitis, bacterial and atypical pneumonia), skin and soft tissues, mycobacterial infection (M.avium complex, M.cansasii, M.marinom, M.leprae), peptic ulcer duodenum and stomach caused by Helicobacter pylori (combination therapy).
Contraindications
Hypersensitivity, severe liver disease, porphyria, pregnancy and breastfeeding.
Side effect
Nausea, vomiting, change in taste, abdominal pain, diarrhea, pseudomembranous colitis, stomatitis, glossitis, dizziness, headache, anxiety, fear, insomnia, nightmares, increased activity of liver enzymes, cholestatic jaundice, allergic (urticaria, Stevens syndrome - Johnson et al.) and anaphylactoid reactions.
Interaction
Increases the concentration in the blood of drugs metabolized in the liver with the participation of enzymes of the cytochrome P450 complex: warfarin and other indirect anticoagulants, carbamazepine, theophylline, astemizole, cisapride, thiazolam, midazolam, cyclosporine, digoxin, ergot alkaloids, etc., reduces the absorption of zidovudine.
Directions for use and dosage
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 clarithromycin suspension for non-mycobacterial infections in 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.
Overdose
Symptoms: nausea, vomiting, diarrhea. Treatment: gastric lavage, symptomatic therapy. Hemodialysis and peritoneal dialysis are not effective.
special instructions
Prescribe with caution against drugs metabolized by the liver (it is recommended to measure their concentration in the blood). In case of combination with warfarin or other indirect anticoagulants, it is necessary to monitor the prothrombin time. If you have a history of heart disease, simultaneous use with terfenadine, cisapride, or astemizole is not recommended.
Storage conditions
List B. In a place protected from light, at room temperature.

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

Keep out of the reach of children.

Expiration date from date of manufacture

Product description

Powder for the preparation of a suspension for oral administration, white or almost white, granular, with a fruity aroma; When shaken with water, an opaque suspension of white or almost white color with a fruity aroma is formed.

pharmachologic effect

Klacid is an antibiotic of the macrolide group. Clarithromycin inhibits protein synthesis in microbial cells by interacting with the 50S ribosomal subunit of bacteria. Highly active against a wide range of aerobic, anaerobic, gram-positive and gram-negative bacteria.
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 the high effectiveness of clarithromycin against Legionella pneumophila and Mycoplasma pneumoniae.
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; other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae (TWAR), Chlamydia trachomatis, mycobacteria Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium avium complex (MAC): Mycobacterium avium, Mycobacferium intracellulare.
Enterobacteriaceae, Pseudomonas spp., as well as other gram-negative bacteria that do not degrade lactose are insensitive to clarithromycin.
The production of b-lactamase does not affect the activity of clarithromycin. Most strains of staphylococci resistant to methicillin and oxacillin are also resistant to clarithromycin.
Clarithromycin is effective in vitro against most strains of the following microorganisms (however, the safety and effectiveness of clarithromycin in clinical practice not 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: Bordeteila pertussis, Pasteurella multocida; anaerobic gram-positive microorganisms: Clostridium perfringens, Peptococcus niger, Propionibacterium acnes; anaerobic gram-negative microorganisms: Bacteroides melaninogenicus; Borrelia burgdorferi, Treponema pallidum, Campylobacter jejuni.
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.
Extended-release tablets are a homogeneous crystalline base, which, when passed through the gastrointestinal tract, ensures a long-term release of the active substance.

Pharmacokinetics

Suction

The first data on pharmacokinetics were obtained from the study of clarithromycin tablets. The drug is quickly absorbed into gastrointestinal tract. The absolute bioavailability of clarithromycin 500 mg tablets is approximately 50%. Food slightly delayed the onset of absorption and the formation of the active metabolite of 14-OH-clarithromycin, but did not affect the bioavailability of the drug.

Distribution, metabolism and excretion

In in vitro studies, clarithromycin binding to plasma proteins averaged approximately 70% at clinically relevant concentrations ranging from 0.45 to 4.5 mcg/ml.

Healthy

The bioavailability and pharmacokinetics of clarithromycin suspension were studied in healthy adults and children. When administered once in adults, the bioavailability of the suspension was equivalent to or slightly greater than that of the tablets (both 250 mg dose). As with tablets, food slightly delayed the absorption of clarithromycin suspension but did not affect the overall bioavailability of the drug. The maximum concentration (Cmax), area under the concentration-time curve (AUC) and half-life (T1/2) of clarithromycin when taking the pediatric suspension (after meals) were 0.95 mcg/ml, 6.5 mcg.h/ml and 3.7 hours, respectively, and when taking a 250 mg tablet (on an empty stomach) - 1.1 mcg/ml, 6.3 mcg.h/ml and 3.3 hours, respectively.

When clarithromycin suspension was administered at a dose of 250 mg every 12 hours in adults, steady-state blood concentrations were achieved by the fifth dose. The pharmacokinetic parameters were as follows: Cmax - 1.98 µg/ml, AUC - 11.5 µg/h/ml, time to reach maximum concentration (Tmax) - 2.8 hours and T1/2 - 3.2 hours for clarithromycin and, respectively, 0.67, 5.33, 2.9 and 4.9 for 14-OH-clarithromycin.

In healthy subjects, serum concentrations reached a maximum within 2 hours after ingestion on an empty stomach. When taking the drug in tablet form at a dose of 250 mg every 12 hours, peak equilibrium concentrations of clarithromycin in the blood serum were achieved within 2-3 days and were approximately 1 mcg/ml. Corresponding peak concentrations for the 500 mg dose every 12 hours ranged from 2 mcg/mL to 3 mcg/mL.

The half-life of clarithromycin was 3-4 hours when taking 250 mg tablets every 12 hours, but increased to 5-7 hours after taking 500 mg tablets every 12 hours. The maximum steady-state concentration of the main metabolite, 14-OH-clarithromycin, is about 0.6 μg/ml, and the half-life when taking the drug at a dose of 250 mg every 12 hours is 5-6 hours. When clarithromycin is taken at a dose of 500 mg every 12 hours, the maximum steady-state concentration of 14-OH-clarithromycin is slightly higher (up to 1 mcg/ml), and the half-life is about 7 hours. When both doses are used, steady-state metabolite concentrations are usually achieved within 2-3 days. When clarithromycin is used at a dose of 250 mg every 12 hours, approximately 20% of the dose is excreted unchanged by the kidneys. When clarithromycin is taken at a dose of 500 mg every 12 hours, approximately 30% of the dose is excreted unchanged by the kidneys. The renal clearance of clarithromycin is not significantly dependent on dose and is approximately equal to normal speed glomerular filtration. The main metabolite detected in urine is 14-OH-clarithromycin, which accounts for 10-15% of the dose (250 or 500 mg every 12 hours).

Patients

Clarithromycin and its metabolite 14-OH-clarithromycin quickly penetrate into body tissues and fluids. Tissue concentrations are usually several times higher than serum concentrations. The table provides examples of tissue and serum concentrations:

Concentrations (250 mg every 12 hours)

Type of fabric

Tissue (µg/g)

Serum (µg/ml)

Tonsils

In children requiring oral antibiotic treatment, clarithromycin showed high bioavailability, with a pharmacokinetic profile similar to that in adults taking the same dosage form. The drug is quickly and well absorbed in children. Food slightly delays the absorption of clarithromycin, but does not significantly affect its bioavailability or pharmacokinetic properties. The equilibrium parameters of the pharmacokinetics of clarithromycin, achieved after 5 days (ninth dose), were as follows: Cmax - 4.60 μg/ml, AUC - 15.7 μg.h/ml and Tmax - 2.8 hours; the corresponding values ​​for the 14-OH-clarithromycin metabolite were 1.64 μg/ml, 6.69 μg.h/ml and 2.7 h, respectively. The estimated half-lives of clarithromycin and its metabolite are 2.2 and 4.3 hours, respectively.

In patients with otitis media, 2.5 hours after taking the fifth dose (7.5 mg/kg twice daily), the average concentrations of clarithromycin and its metabolite in the middle ear fluid were 2.53 and 1.27 mcg/g. Concentrations of the drug and its metabolite were twice the serum concentrations.

Liver dysfunction

Steady-state concentrations of clarithromycin in patients with hepatic impairment did not differ from those in healthy subjects, while concentrations of 14-OH-clarithromycin were lower. The decreased formation of 14-OH-clarithromycin in patients with hepatic impairment was at least partially offset by the increased renal clearance of clarithromycin compared with that in healthy subjects.

Renal dysfunction

The pharmacokinetics of clarithromycin also changed in patients with impaired renal function who received the drug in repeated doses of 500 mg. In these patients, plasma concentrations, half-life, maximum concentration (Cmax), minimum concentration (Cmax) and AUC of clarithromycin and its 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 (see section "Dosage and Administration").

Elderly patients

In elderly patients, the concentration of clarithromycin and its metabolite 14-OH-clarithromycin in the blood was higher, and elimination was slower than in the group of young people. However, after adjustment for renal creatinine clearance (CR), there were no differences in both groups. Thus, the main influence on the pharmacokinetic parameters of clarithromycin is renal function, and not age.

Patients with mycobacterial infections

Steady-state concentrations of clarithromycin and 14-OH-clarithromycin in patients with HIV infection receiving clarithromycin in usual doses (tablets for adults, suspension for children) were similar to those in healthy people. However, when clarithromycin is taken in higher doses, which may be required to treat mycobacterial infections, concentrations of the antibiotic may be significantly higher than usual.

In children with HIV infection taking clarithromycin at a dose of 15-30 mg/kg/day in two doses, steady-state Cmax values ​​typically ranged from 8 to 20 mcg/ml. However, in children with HIV infection who received a clarithromycin suspension at a dose of 30 mg/kg/day in two doses, Cmax reached 23 μg/ml. When taking the drug in higher doses, a prolongation of the half-life was observed compared with that in healthy people receiving clarithromycin at usual doses. Increased plasma concentrations and prolongation of the half-life when using clarithromycin at higher doses are associated with the nonlinear pharmacokinetics of the drug.

Indications for use

Infectious and inflammatory diseases caused by microorganisms sensitive to clarithromycin:

Lower respiratory tract infections (such as bronchitis, pneumonia);

Upper respiratory tract infections (such as pharyngitis, sinusitis);

Skin and soft tissue infections (such as folliculitis, inflammation subcutaneous tissue, erysipelas);

Disseminated or localized mycobacterial infections caused by Mycobacterium avium and Mycobacterium intracellulare;

Localized infections caused by Mycobacterium chelonae, Mycobacterium fortuitum and Mycobacterium kansasii;

Acute otitis media.

Use during pregnancy and lactation

The safety of clarithromycin during pregnancy and breastfeeding has not been established.

The use of clarithromycin during pregnancy (especially in the first trimester) is possible only if there is no alternative therapy, and the potential benefit to the mother outweighs the potential risk to the fetus.

Clarithromycin is eliminated from breast milk. If necessary, during lactation breast-feeding needs to stop.

special instructions

Long-term use of antibiotics can lead to the formation of colonies with an increased number of insensitive bacteria and fungi. In case of superinfection, appropriate therapy must be prescribed.

Liver dysfunction (increased liver enzyme activity in the blood, hepatocellular and/or cholestatic hepatitis with or without jaundice) has been reported with the use of clarithromycin. Liver dysfunction can be severe but is usually reversible. There have been cases of fatal liver failure, mainly associated with the presence of serious concomitant diseases and/or concomitant use of other medicines. If signs and symptoms of hepatitis appear, such as anorexia, jaundice, dark urine, itching, abdominal tenderness on palpation, clarithromycin therapy should be stopped immediately.

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

When treated with almost all antibacterial agents, including clarithromycin, cases of pseudomembranous colitis have been described, the severity of which can range from mild to life-threatening. Antibacterial drugs can change normal microflora intestines, which can lead to the growth of C. difficile. Pseudomembranous colitis caused by Clostridium difficile should be suspected in all patients who experience diarrhea after using antibacterial agents. After a course of antibiotic therapy, careful medical monitoring of the patient is necessary. Cases of the development of pseudomembranous colitis 2 months after taking antibiotics have been described.

Clarithromycin should be used with caution in patients with coronary disease heart disease (CHD), severe heart failure, hypomagnesemia, severe bradycardia (less than 50 beats/min), as well as when used simultaneously with class 1A antiarrhythmic drugs (quinidine, procainamide) and III class(dofetilide, amiodarone, sotalol). In these conditions and when taking clarithromycin concomitantly with these drugs, the electrocardiogram should be regularly monitored for prolongation of the QT interval.

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

Given the increasing resistance of Streptococcus pneumoniae to macrolides, it is important to perform susceptibility testing when prescribing clarithromycin to patients with community-acquired pneumonia. For hospital-acquired pneumonia, clarithromycin should be used in combination with appropriate antibiotics.

Mild to moderate skin and soft tissue infections are most often caused by Staphylococcus aureus and Streptococcus pyogenes. Moreover, both pathogens can be resistant to macrolides. Therefore, it is important to conduct a sensitivity test.

Macrolides can be used for infections caused by Coiynebacterium minutissimum, acne vulgaris and erysipelas, as well as in situations where penicillin cannot be used.

If acute hypersensitivity reactions such as anaphylactic reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis and drug rash with eosinophilia and systemic symptoms (DRESS syndrome) occur, clarithromycin should be stopped immediately and appropriate therapy should be initiated. In case of combined use with warfarin or other indirect anticoagulants, it is necessary to monitor the INR and prothrombin time (see section "Interaction with other drugs").

When prescribing the drug to patients with diabetes mellitus it is necessary to take into account that the drug Klacid®, powder for the preparation of an oral suspension of 125 mg/5 ml, contains sucrose (1 ml of suspension contains 0.055 XE or 0.55 g of sucrose).

With caution (Precautions)

Moderate to severe renal failure;

Moderate to severe liver failure;

Concomitant use of clarithromycin with benzodiazepines, such as alprazolam, triazolam, midazolam for intravenous use (see "Interaction with other drugs");

Concomitant use of clarithromycin with other ototoxic drugs, especially aminoglycosides (see section "Interaction with other drugs");

Concomitant use with drugs that are metabolized by the CYP3A isoenzyme, for example, carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants (for example, warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine (see section "Interaction with other drugs" drugs");

Concomitant use with drugs that induce the CYP3A4 isoenzyme, for example, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort (see section "Interaction with other drugs");

Concomitant use of clarithromycin with statins that do not depend on the metabolism of the CYP3A isoenzyme (for example, fluvastatin) (see section "Interaction with other drugs");

Concomitant use with blockers of “slow” calcium channels that are metabolized by the CYP3A4 isoenzyme (for example, verapamil, amlodipine, diltiazem);

Patients with coronary heart disease (CHD), severe heart failure, hypomagnesemia, severe bradycardia (less than 50 beats/min), as well as patients simultaneously taking class IA (quinidine, procainamide) and class III antiarrhythmic drugs (dofetilide, amiodarone, sotalol) ;

Pregnancy;

Diabetes mellitus (the drug contains sucrose).

Contraindications

Hypersensitivity to clarithromycin, other components of the drug and other macrolides;

Simultaneous use of clarithromycin with the following drugs: astemizole, cisapride, pimozide, terfenadine (see section "Interaction with other drugs");

Simultaneous use of clarithromycin with ergot alkaloids, for example, ergotamine, dihydroergotamine (see section "Interaction with other drugs");

Concomitant use of clarithromycin with midazolam for oral use (see section "Interaction with other drugs");

Concomitant use of clarithromycin with HMG-CoA reductase inhibitors (statins), which are largely metabolized by the CYP3A4 isoenzyme (lovastatin, simvastatin), due to an increased risk of myopathy, including rhabdomyolysis (see section "Interaction with other drugs");

Concomitant use of clarithromycin with colchicine;

Concomitant use of clarithromycin with ticagrelor or ranolazine;

History of QT prolongation, ventricular arrhythmia or torsade de pointes;

Hypokalemia (risk of QT prolongation);

Severe liver failure occurring simultaneously with renal failure;

A history of cholestatic jaundice/hepatitis that developed during the use of clarithromycin (see section "Special Instructions");

Congenital fructose intolerance, sucrase-isomaltase deficiency, glucose-galactose malabsorption syndrome;

Porphyria;

Breastfeeding period.

Directions for use and doses

For oral administration. The prepared suspension can be taken regardless of food intake, including with milk.

Preparation for use: gradually add water to the bottle to the mark and shake to obtain 60 ml of a suspension containing 125 mg of clarithromycin per 5 ml. The prepared suspension can be stored for 14 days at room temperature (from 15 °C to 30 °C). Before each dose, the suspension should be shaken well.

Dose for non-mycobacterial infections

The recommended daily dose of clarithromycin suspension for non-mycobacterial infections in children is 7.5 mg/kg 2 times a day (maximum - 500 mg 2 times a day). The usual duration of treatment is 5-10 days, depending on the pathogen and the severity of the condition.

Body weight*, kg

Single dose when taken 2 times a day, ml (7.5 mg/kg 2 times a day)

* In children with body weight
Dose for mycobacterial infections

In children with disseminated or localized mycobacterial infections (M avium, M. intracellulare, M. chelonae, M. fortuitum, M. kansasii), the recommended daily dose of clarithromycin is 7.5-15 mg/kg 2 times a day.

Treatment with clarithromycin should be continued as long as the clinical effect persists. Clarithromycin should be prescribed in combination with other antimicrobial drugs active against these pathogens.

Body weight*, kg

Single dose when taken 2 times a day, ml

7.5 mg/kg 2 times a day

15 mg/kg 2 times a day

* In children with body weight
Dose for patients with impaired renal function

In children with creatinine clearance less than 30 ml/min, the dose of clarithromycin should be halved (for example, 125 mg per day or 125 mg 2 times per day for more severe infections). In such cases, the course of treatment should not exceed 14 days, although the usual duration of treatment is 5-10 days.

Overdose

Symptoms: Taking a large dose of clarithromycin may cause 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: in case of overdose, the unabsorbed drug should be removed from the gastrointestinal tract (gastric lavage, activated charcoal, etc.) and symptomatic therapy should be carried out. Hemodialysis and peritoneal dialysis do not have a significant effect on the concentration of clarithromycin in serum, which is also typical for other macrolide drugs.

Side effect

Classification of adverse reactions by frequency of development (number of registered cases/number of patients): very often (≥1/10), often (≥1/100,
Allergic reactions

Common: rash.

Uncommon: anaphylactoid reaction1, hypersensitivity, bullous dermatitis1, pruritus, urticaria, maculopapular rash3.

Not known: anaphylactic reaction, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome).

From the outside nervous system

Common: headache, insomnia.

Uncommon: loss of consciousness1, dyskinesia1, dizziness, drowsiness, tremor, anxiety, increased excitability3.

Frequency unknown: convulsions, psychotic disorders, confusion, depersonalization, depression, disorientation, hallucinations, dream disturbances (“nightmare” dreams), paresthesia, mania.

From the skin

Common: intense sweating.

Frequency unknown: acne, hemorrhages.

From the urinary system

Frequency unknown: renal failure, interstitial nephritis.

Metabolism and nutrition

Uncommon: anorexia, decreased appetite.

From the musculoskeletal system

Uncommon: muscle spasm3, musculoskeletal stiffness1, myalgia2.

Frequency unknown: rhabdomyolysis2*, myopathy.

From the outside digestive system

Common: diarrhea, vomiting, dyspepsia, nausea, abdominal pain.

Uncommon: esophagitis1, gastroesophageal reflux disease2, gastritis, proctalgia2, stomatitis, glossitis, bloating4, constipation, dry mouth, belching, flatulence, cholestasis4, hepatitis incl. cholestatic or hepatocellular4.

Frequency unknown: acute pancreatitis, discoloration of the tongue and teeth, liver failure, cholestatic jaundice.

From the respiratory system

Uncommon: asthma1, epistaxis2, pulmonary embolism1.

From the senses

Common: dysgeusia, taste perversion.

Uncommon: vertigo, hearing loss, tinnitus.

Frequency unknown: deafness, ageusia (loss of taste), parosmia, anosmia.

From the cardiovascular system

Common: vasodilation1.

Uncommon: cardiac arrest1, atrial fibrillation1, prolongation of the QT interval on the electrocardiogram, extrasystole1, atrial flutter.

Frequency unknown: ventricular tachycardia, including pirouette type.

Laboratory indicators

Common: abnormal liver function test.

Uncommon: increased creatinine concentration1, increased urea concentration1, change in albumin-globulin ratio1, leukopenia, neutropenia4, eosinophilia4, thrombocythemia3, increased activity of: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gammaglutamyltransferase (GGTP)4, alkaline phosphatase4, lactate dehydrogenase (LDH) 4.

Frequency unknown: agranulocytosis, thrombocytopenia, increased international normalized ratio (INR), prolongation of prothrombin time, change in urine color, increased bilirubin concentration in the blood.

General disorders

Very common: phlebitis at the injection site1.

Common: pain at the injection site1, inflammation at the injection site1.

Uncommon: malaise4, pyrexia3, asthenia, chest pain4, chills4, fatigue4.

Uncommon: cellulitis1, candidiasis, gastroenteritis2, secondary infections (including vaginal)3.

Frequency unknown: pseudomembranous colitis, erysipelas.

Immunosuppressed patients

In patients with AIDS and other immunodeficiencies receiving clarithromycin in higher doses over a long period of time to treat mycobacterial infections, it is often difficult to distinguish unwanted effects medication for symptoms HIV infections or concomitant disease.

The most common adverse events in patients taking a daily dose of clarithromycin equal to 1000 mg were: nausea, vomiting, taste disturbance, abdominal pain, diarrhea, rash, flatulence, headache, constipation, hearing loss, increased AST and ALT activity in blood. Low incidence adverse events such as shortness of breath, insomnia and dry mouth were also reported.

In patients with suppressed immunity, laboratory parameters were assessed, analyzing their significant deviations from the norm ( sharp increase or decrease). Based on this criterion, a significant increase in AST and ALT activity in the blood, as well as a decrease in the number of leukocytes and platelets, was observed in 2-3% of patients receiving clarithromycin at a dose of 1000 mg daily. Increases in residual urea nitrogen concentrations have also been reported in a small number of patients.

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

1 Reports of these adverse reactions were received only with the use of the drug Klacid®, lyophilisate for the preparation of solution for infusion.

2 Reports of these adverse reactions were received only with the use of the drug Klacid®, extended-release film-coated tablets.

3 Reports of these adverse reactions were received only with the use of the drug Klacid®, powder for the preparation of suspension for oral administration.

4 Reports of these adverse reactions were received only when using the drug Klacid®, film-coated tablets.

Compound

Clarithromycin 125 mg
Excipients: carbomer (carbopol 974P) - 75 mg, povidone K90 - 17.5 mg, hypromellose phthalate - 152.1 mg, castor oil - 16.1 mg, silicon dioxide - 5 mg, maltodextrin - 285.7 mg, sucrose - 2748.3 mg, titanium dioxide - 35.7 mg, xanthan gum - 3.8 mg, fruit flavoring - 35.7 mg, potassium sorbate - 20 mg, lemon acid anhydrous - 4.2 mg.

Interaction with other drugs

The use of the following drugs with clarithromycin is contraindicated due to the potential for serious side effects

Cisapride, pimozide, terfenadine and astemizole

At joint reception clarithromycin with cisapride, pimozide, terfenadine or astemizole has been reported to increase the concentration of the latter in the blood plasma, which can lead to prolongation of the QT interval and the appearance of cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation and torsade de pointes (see section "Contraindications" ),

Ergot alkaloids

Post-marketing studies show that when clarithromycin is used together with ergotamine or dihydroergotamine, the following effects associated with acute poisoning with ergotamine drugs are possible: vascular spasm, ischemia of the limbs and other tissues, including the central nervous system. Concomitant use of clarithromycin with ergot alkaloids is contraindicated (see section “Contraindications”).

HMG-CoA reductase inhibitors (statins)

Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated (see section "Contraindications") due to the fact that these statins are largely metabolized by the CYP3A4 isoenzyme, and combined use with clarithromycin increases their serum concentrations, which leads to an increased risk of developing myopathy, including Rhabdomyolysis Cases of rhabdomyolysis have been reported in patients taking clarithromycin concomitantly with these drugs. If clarithromycin is necessary, lovastatin or simvastatin should be discontinued during therapy.

Clarithromycin should be used with caution in combination therapy with other statins. It is recommended to use statins that are independent of the metabolism of the CYP3A isoenzyme (for example, fluvastatin). If co-administration is necessary, it is recommended to take lowest dose statin The development of signs and symptoms of myopathy should be monitored.

Effect of other drugs on clarithromycin

Drugs that are inducers of the CYP3A isoenzyme (for example, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort) can induce the metabolism of clarithromycin. This may result in subtherapeutic concentrations of clarithromycin, resulting in reduced effectiveness. In addition, it is necessary to monitor the concentration of the CYP3A inducer in the blood plasma, which may increase due to the inhibition of the CYP3A isoenzyme by clarithromycin. When rifabutin and clarithromycin were used together, an increase in plasma concentrations of rifabutin and a decrease in serum concentrations of clarithromycin were observed with an increased risk of developing uveitis.

The following drugs have a proven or suspected effect on clarithromycin plasma concentrations; if used together with clarithromycin, dosage adjustments or switching to alternative treatment may be required

Efavirenz, nevirapine, rifampicin, rifabutin and rifapentine

Strong inducers of the cytochrome P450 system, such as efavirenz, nevirapine, rifampicin, rifabutin and rifapentine, may accelerate the metabolism of clarithromycin and, thus, reduce clarithromycin plasma concentrations and weaken therapeutic effect, and at the same time increase the concentration of 14-OH-clarithromycin, a metabolite that is also microbiologically active. Since the microbiological activity of clarithromycin and 14-OH-clarithromycin differs against different bacteria, the therapeutic effect may be reduced when clarithromycin is used together with enzyme inducers.

Etravirine

The concentration of clarithromycin decreases with the use of etravirine, but the concentration of the active metabolite 14-OH-clarithromycin increases. Because 14-OH-clarithromycin has little activity against Mycobacterium avium complex (MAC) infections, overall activity against these pathogens may be altered, and alternative treatments should be considered for the treatment of MAC.

Fluconazole

Coadministration of fluconazole 200 mg daily and clarithromycin 500 mg twice daily in 21 healthy volunteers resulted in an increase in the mean clarithromycin minimum steady-state concentration (Cmin) and AUC by 33% and 18%, respectively. However, co-administration did not significantly affect the average steady-state concentration of the active metabolite 14-OH-clarithromycin. No dose adjustment of clarithromycin is required when taking fluconazole concomitantly.

Ritonavir

A pharmacokinetic study showed that coadministration of ritonavir 200 mg every eight hours and clarithromycin 500 mg every 12 hours resulted in a marked suppression of the metabolism of clarithromycin. When co-administered with ritonavir, clarithromycin Cmax increased by 31%, Cmin increased by 182% and AUC increased by 77%. Complete suppression of the formation of 14-OH-clarithromycin was noted. Due to the wide therapeutic range of clarithromycin, dose reduction is not required in patients with normal renal function. In patients with renal failure, it is advisable to consider the following dose adjustment options: with CC 30-60 ml/min, the dose of clarithromycin should be reduced by 50%; with CC less than 30 ml/min, the dose of clarithromycin should be reduced by 75%. Ritonavir should not be co-administered with clarithromycin in doses exceeding 1 g/day.

Effect of clarithromycin on other drugs

Antiarrhythmic drugs (quinidine and disopyramide)

Torsade de pointes-type ventricular tachycardia may occur with the combined use of clarithromycin and quinidine or disopyramide. When clarithromycin is coadministered with these drugs, the electrocardiogram should be regularly monitored for prolongation of the QT interval, and serum concentrations of these drugs should also be monitored.

During post-marketing use, cases of hypoglycemia have been reported during co-administration of clarithromycin and disopyramide. It is necessary to monitor the concentration of glucose in the blood while using clarithromycin and disopyramide.

Oral hypoglycemic agents/insulin

When clarithromycin is used together with oral hypoglycemic agents (for example, sulfonylureas) and/or insulin, severe hypoglycemia may occur. Concomitant use of clarithromycin with certain hypoglycemic drugs (for example, nateglinide, pioglitazone, repaglinide and rosiglitazone) may lead to inhibition of the CYP3A isoenzyme by clarithromycin, which may result in hypoglycemia. Careful monitoring of glucose concentrations is recommended.

Interactions due to CYP3A isoenzyme

Co-administration of clarithromycin, which is known to inhibit the CYP3A isoenzyme, and drugs primarily metabolized by the CYP3A isoenzyme, may be associated with a mutual increase in their concentrations, which may increase or prolong both therapeutic and side effects. Clarithromycin should be used with caution in patients receiving drugs that are substrates of the CYP3A isoenzyme, especially if these drugs have a narrow therapeutic index (for example, carbamazepine) and/or are extensively metabolized by this enzyme. If necessary, the dose of the drug taken together with clarithromycin should be adjusted. Also, whenever possible, serum concentrations of drugs primarily metabolized by the CYP3A isoenzyme should be monitored.

The following drugs/classes are metabolized by the same CYP3A isoenzyme as clarithromycin, for example, alprazolam, carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, midazolam, omeprazole, indirect anticoagulants (eg, warfarin), quinidine, rifabutin, sildenafil, tacrolimus, triazolam and vinblastine. Also, agonists of the CYP3A isoenzyme include the following drugs that are contraindicated for combined use with clarithromycin: astemizole, cisapride, pimozide, terfenadine, lovastatin, simvastatin and ergot alkaloids (see section "Contraindications"). Drugs that interact in a similar way through other isoenzymes within cytochrome P450 systems include phenytoin, theophylline and valproic acid.

Indirect anticoagulants

When taking warfarin and clarithromycin together, bleeding and a marked increase in INR and prothrombin time are possible. In case of combined use with warfarin or other indirect anticoagulants, it is necessary to monitor the INR and prothrombin time.

Omeprazole

Clarithromycin (500 mg every 8 hours) was studied in healthy adult volunteers in combination with omeprazole (40 mg daily). When clarithromycin and omeprazole were co-administered, steady-state plasma concentrations of omeprazole were increased (Cmax, AUC0-24 and T1/2 increased by 30%, 89% and 34%, respectively). The mean 24-hour gastric pH was 5.2 when omeprazole was taken alone and 5.7 when omeprazole was taken with clarithromycin.

Sildenafil, tadalafil and vardenafil

Each of these phosphodiesterase inhibitors is metabolized, at least in part, by the CYP3A isoenzyme. At the same time, the CYP3A isoenzyme can be inhibited in the presence of clarithromycin. Concomitant use of clarithromycin with sildenafil, tadalafil or vardenafil may result in increased phosphodiesterase inhibitory effects. When using these drugs together with clarithromycin, consider reducing the dose of sildenafil, tadalafil and vardenafil.

Theophylline, carbamazepine

When clarithromycin and theophylline or carbamazepine are used together, the concentration of these drugs in the systemic circulation may increase.

Tolterodine

The primary metabolism of tolterodine occurs through the 2D6 isoform of cytochrome P450 (CYP2D6). However, in part of the population lacking the CYP2D6 isoenzyme, metabolism occurs through the CYP3A isoenzyme. In this population, inhibition of CYP3A results in significantly higher serum tolterodine concentrations. In populations that are poor metabolizers of CYP2D6, a dose reduction of tolterodine may be required in the presence of CYP3A inhibitors such as clarithromycin.

Benzodiazepines (eg, alprazolam, midazolam, triazolam)

When midazolam was co-administered with clarithromycin tablets (500 mg twice daily), an increase in midazolam AUC was observed: 2.7 times after intravenous administration midazolam and 7 times after oral administration. Concomitant use of clarithromycin with oral midazolam is contraindicated. If intravenous midazolam is used concomitantly with clarithromycin, the patient's condition should be carefully monitored for possible dose adjustment. The same precautions should be applied to other benzodiazepines that are metabolized by CYP3A, including triazolam and alprazolam. For benzodiazepines whose elimination is not dependent on the CYP3A isoenzyme (temazepam, nitrazepam, lorazepam), a clinically significant interaction with clarithromycin is unlikely.

When clarithromycin and triazolam are used together, effects on the central nervous system (CNS), such as drowsiness and confusion, are possible. Therefore, if coadministration occurs, it is recommended to monitor for symptoms of CNS impairment.

Interactions with other drugs

Aminoglycosides

When taking clarithromycin concomitantly with other ototoxic drugs, especially aminoglycosides, caution should be exercised and monitoring of vestibular and hearing aids both during therapy and after its completion.

Colchicine

Colchicine is a substrate of both CYP3A and the P-glycoprotein (Pgp) transporter protein. It is known that clarithromycin and other macrolides are inhibitors of the CYP3A and Pgp isoenzymes. When clarithromycin and colchicine are taken together, inhibition of Pgp and/or CYP3A may result in increased effects of colchicine. The development of clinical symptoms of colchicine poisoning should be monitored. There have been post-marketing reports of cases of colchicine poisoning when taken concomitantly with clarithromycin, most often in elderly patients.

Some of the reported cases occurred in patients suffering from kidney failure. Some cases were reported to be fatal.

The simultaneous use of clarithromycin and colchicine is contraindicated (see section “Contraindications”).

Digoxin

Digoxin is suspected to be a Pgp substrate. Clarithromycin is known to inhibit Pgp. When clarithromycin and digoxin are co-administered, inhibition of Pgp by clarithromycin may result in increased effects of digoxin. Coadministration of digoxin and clarithromycin may also result in increased serum concentrations of digoxin. Some patients have experienced clinical symptoms of digoxin toxicity, including potentially fatal arrhythmias. Serum digoxin concentrations should be carefully monitored when clarithromycin and digoxin are coadministered.

Zidovudine

Concomitant use of clarithromycin tablets and oral zidovudine by adult HIV-infected patients may result in decreased steady-state zidovudine concentrations.

Because clarithromycin interferes with the oral absorption of zidovudine, the interaction can be largely avoided by taking clarithromycin and zidovudine 4 hours apart.

This interaction was not observed in HIV-infected children taking clarithromycin pediatric suspension with zidovudine or dideoxyinosine. Since clarithromycin may interfere with the absorption of zidovudine when administered concomitantly orally in adult patients, such an interaction is unlikely to occur when clarithromycin is used intravenously.

Phenytoin and valproic acid

There is evidence of interactions between CYP3A inhibitors (including clarithromycin) and drugs that are not metabolized by CYP3A (phenytoin and valproic acid). For these drugs, when used together with clarithromycin, it is recommended to determine their serum concentrations, as there are reports of their increase.

Bidirectional drug interactions

Atazanavir

Clarithromycin and atazanavir are both substrates and inhibitors of the CYP3A isoenzyme. There is evidence of a bidirectional interaction between these drugs.

Coadministration of clarithromycin (500 mg twice daily) and atazanavir (400 mg once daily) may result in a twofold increase in clarithromycin exposure and a 70% decrease in 14-OH-clarithromycin exposure, with a 28% increase in atazanavir AUC. Due to the wide therapeutic range of clarithromycin, reducing its dose in patients with normal function no kidneys required. In patients with moderate renal failure (creatinine clearance 30-60 ml/min), the dose of clarithromycin should be reduced by 50%. In patients with CC less than 30 ml/min, the dose of clarithromycin should be reduced by 75% using the appropriate dosage form of clarithromycin. Clarithromycin in doses exceeding 1000 mg per day should not be used in conjunction with protease inhibitors.

Blockers of "slow" calcium channels

When using clarithromycin simultaneously with blockers of “slow” calcium channels that are metabolized by the CYP3A4 isoenzyme (for example, verapamil, amlodipine, diltiazem), caution should be exercised as there is a risk of arterial hypotension. Plasma concentrations of clarithromycin, as well as slow calcium channel blockers, may increase with simultaneous use. Arterial hypotension, bradyarrhythmia and lactic acidosis are possible when taking clarithromycin and verapamil simultaneously.

Itraconazole

Clarithromycin and itraconazole are substrates and inhibitors of the CYP3A isoenzyme, which determines the bidirectional interaction of the drugs. Clarithromycin may increase plasma concentrations of itraconazole, while itraconazole may increase plasma concentrations of clarithromycin. Patients taking itraconazole and clarithromycin concomitantly should be closely monitored for symptoms of increased or prolonged pharmacological effects of these drugs.

Saquinavir

Clarithromycin and saquinavir are substrates and inhibitors of the CYP3A isoenzyme, which determines the bidirectional interaction of the drugs. Concomitant administration of clarithromycin (500 mg twice daily) and saquinavir (soft gelatin capsules, 1200 mg three times daily) in 12 healthy volunteers increased the AUC and Cmax of saquinavir by 177% and 187%, respectively, compared with saquinavir administration alone. separately. The AUC and Cmax values ​​of clarithromycin were approximately 40% higher than with clarithromycin monotherapy. When these two drugs are used together for a limited time at the doses/formulations indicated above, no dose adjustment is required. Results from drug interaction studies using saquinavir soft gelatin capsules may not be consistent with the effects observed with saquinavir hard gelatin capsules. The results of drug interaction studies with saquinavir monotherapy may not be consistent with the effects observed with saquinarine/ritonavir therapy. When taking saquinavir with ritonavir, consider the potential effect of ritonavir on clarithromycin.

Release form

Powder for the preparation of a suspension for oral administration, white or almost white, granular, with a fruity aroma; When shaken with water, an opaque suspension of white or almost white color with a fruity aroma is formed.
5 ml of ready-made suspension.
clarithromycin 125 mg
Excipients: carbomer (carbopol 974P) - 75 mg, povidone K90 - 17.5 mg, hypromellose phthalate - 152.1 mg, castor oil - 16.1 mg, silicon dioxide - 5 mg, maltodextrin - 285.7 mg, sucrose - 2748.3 mg, titanium dioxide - 35.7 mg, xanthan gum - 3.8 mg, fruit flavoring - 35.7 mg, potassium sorbate - 20 mg, anhydrous citric acid - 4.2 mg.
42.3 g - plastic bottles with a volume of 60 ml (1) complete with a dosing spoon or dosing syringe - cardboard packs.

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” - we can assume that the infection is 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 hours 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 other than 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.

In children with CC, 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

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 unwanted reactions included headache, taste disturbances, and transient increases in liver enzyme activity. 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.

Others: 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

Contraindications to the use of the drug

- severe liver dysfunction;

- severe renal dysfunction (KR)

- 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 exceeds possible harm for 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

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 medicinal substances under the influence of this system, which may lead to an increase in their 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)

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. 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

Dispensing the drug

On prescription

Manufacturer's country of origin

Basic shelf life (in months)

Method of drug administration

Oral

Nosological classification ICD-10 (name)

Infections caused by other mycobacteria; Erysipelas; Otitis externa, unspecified; Otitis media, unspecified; Acute sinusitis; Acute pharyngitis, unspecified; Acute infections of the upper respiratory tract of multiple and unspecified localization; Pneumonia, unspecified pathogen; Acute respiratory infection lower respiratory tract, unspecified; Chronic pharyngitis; Chronic sinusitis; Bronchitis, not specified as acute or chronic; Duodenal ulcer; Local infection of the skin and subcutaneous tissue, unspecified; Folliculitis; Other specified diseases of the skin and subcutaneous tissue; Lesions of the skin and subcutaneous tissue, unspecified

Pharmacological group ATS (name)

Every time a pediatrician prescribes an antibiotic to a child, the mother has many questions. How effective is the drug? Will strong medicine harm the child? How to correctly calculate the dose so that the antibiotic works without causing side effects? New drugs, such as Klacid, which recently appeared on the pharmaceutical market, are of particular concern. Our review will help you, parents, draw conclusions about the feasibility, effectiveness and possible consequences its application.

Klacid does not kill pathogens, but deprives them of the opportunity to reproduce. This is enough for recovery.

Features of the drug

Modern powerful drug Klacid belongs to the class of macrolides - the least toxic, and therefore the safest antibiotics. The long-familiar and familiar Erythromycin has a similar broad-spectrum effect. However, as evidenced by numerous reviews on parenting forums, Klacid for children is a more effective and convenient remedy. A new generation antibiotic, unlike its predecessor, has a relatively pleasant taste and fruity aroma. And this is important when the baby does not yet understand the purpose of feeding him bitter medicine. In addition, you only need to take it twice, not four times a day, which reduces the risk of side effects and the negative impact of the drug on the delicate child’s body.

IN Lately microbes and pathogens have managed to adapt to antibiotics such as penicillin and cephalosporin, losing sensitivity to them. In this regard, Klacid often turns out to be one of the most effective and at the same time gentle options.

Suspension is the most convenient dosage form for children.

The drug is manufactured by Abbott Laboratories Limited (UK). The price of the medicine in the form of powder for preparing suspensions varies between 300-400 rubles.: The higher the dosage, the higher the cost. Tablets can be bought on average for 600-800 rubles. Their cost also depends on the dosage and number of tablets in the pack.

Analogs

The drug has a number of analogues, which contain the same main substance - clarithromycin. These include Clarbact, Clarithromycin, Fromilid, Exoterin and some others. The possibility of interchangeability of drugs in each specific case can only be confirmed by a pediatrician.

When is this medicine prescribed - indications for use

For children, the drug is prescribed for inflammatory processes in the body caused by a large number varieties of microbes. Prescribing the drug is advisable when:

• typical childhood infections - scarlet fever, whooping cough;
• diseases of the lower respiratory tract - lung abscess, pneumonia, bronchitis;
• upper respiratory tract infections - sore throat, ;
• ENT diseases - otitis media;
• gonorrheal or chlamydial nature;
• ulcerative lesions of the stomach and duodenum (the medicine is used here as part of complex therapy);
• infections of the skin (for example, erysipelas) and soft tissues.

A more detailed list of problems eliminated by Klacid is given in the instructions for its use, which can be found.

Klacid: variety of forms

The antibiotic is produced in the form:

• tablets;
• powder for the preparation of a suspension taken orally;
• powder for preparing a suspension used for infusions (droppers).

Children under the age of three years Klacid is not prescribed in tablet form.

Of course, in the case of child patients, it is better to opt for the Klacid suspension: its semi-liquid consistency is most convenient and pleasant for children.

Many parents naturally have a question: what do the markings on the packages mean: 125, 250, 500? These numbers indicate the amount contained active substance clarithromycin in one tablet or 5 ml of prepared suspension. For example, if it is Klacid 125 powder, then 5 ml of suspension (about a teaspoon) contains 125 ml of the active ingredient. This information is important for correctly calculating the dosage appropriate to the weight and age of the child.

The powder is available in bottles (60 and 100 ml), in which the suspension is convenient to store and dilute.

Operating principle

Klacid acts extremely gently and sparingly: it does not kill pathogenic bacteria, but deprives them of the opportunity to reproduce. At the same time, the medicine has a prolonged effect. Even after taking it, it continues to be in the body for some time and perform its function, inhibiting the growth of microbes.

The effectiveness of the drug is also explained by its ability to accumulate in the same places where 99% of pathogens are usually concentrated - in the lungs and bronchi. Moreover, the antibiotic, unlike its predecessors, has a pronounced anti-inflammatory effect.

Preparation of the suspension and dosage calculation

It’s easy to prepare the suspension: just add water to the bottle and vigorously shake the liquid until the powder granules are completely dissolved. The result should be a white (or almost white) opaque liquid, which should be stored at room temperature (no higher than 30 degrees and away from sun rays) maybe about two weeks.

The bottle must be shaken before each use.

Before giving Klacid to a child, carefully read the instructions. The main criterion for the correct dosage is the patient’s weight. The medicine is given at the rate of 7.5 ml per 1 kg of the patient’s body weight.

The numbers that complement the name of the medicine are also important. Children are usually prescribed Klacid 125 or Klacid 250 suspensions. The suspension drug is prescribed even to patients under two years of age in age-appropriate doses.

Let's consider the option of calculating the dosage of the drug Klacid 250 using a specific example.

The patient is a boy Egor, 8 years old. Child weight - 25 kg. Therefore, for one dose (it is assumed that the medicine is taken twice a day), he needs the amount of syrup that would contain 187.5 ml of clarithromycin: 25 kg × 7.5 ml of the recommended dose per 1 kg of weight. If the drug has a concentration of 250, then 5 ml contains 250 ml of the active substance, i.e. 1 ml of suspension contains 50 ml of clarithromycin (250 ml/5 ml). It turns out that Egor needs to take 3.75 ml of suspension (187.5 ml/50 ml is the dose of clarithromycin required for a particular child/clarithromycin content in 1 ml of the resulting syrup). This is 0.75 teaspoon, i.e. approximately 3/4.

The medication is taken twice a day. It is better to do this in the morning and evening at approximately the same time. Before or after eating - it doesn't matter. A small child can be given the suspension along with milk.

You can add the suspension to milk.

The course lasts from 5 to 10 days. A specific regimen, depending on the severity of the disease and the patient’s response to the medicine, is drawn up by a pediatrician. If there is no improvement in within three days, the drug is discontinued and an adequate replacement is selected.

The maximum permissible daily dose of medication in any case is 500 ml.

It is important to know the symptoms of Klacid overdose:

• dizziness;
• mental changes, in particular, the appearance of signs of paranoia.

The listed signs are grounds for stopping taking the drug and carrying out procedures aimed at removing the patient from a dangerous state of overdose:

• removal from the stomach of the remnants of the drug that have not had time to be absorbed by taking activated carbon;
• peritoneal dialysis;
• hemodialysis.

Side effects and contraindications

Klacid should be used with caution (or completely avoided) for children with problems with the liver, kidneys and biliary tract. When these organs are dysfunctional, the components of the drug are poorly excreted and accumulate in the body, overloading it. The same applies to young patients suffering from arrhythmia and increased anxiety, because the the medicine provokes the release of adrenaline. It is important for parents of children with allergies and asthma to know that Klacid slows down output antihistamines from the body. If a child takes antiallergic drugs constantly, during treatment with macrolides their components may accumulate in excessive (toxic) doses. Be careful - don't get poisoned.

Composition and release form

Granules for preparing a suspension - 5 ml of finished suspension:

• Active ingredients: clarithromycin - 125 mg;
• Excipients: carbomer (carbopol 974P) - 75 mg, povidone K90 - 17.5 mg, silicon dioxide - 5 mg, maltodextrin - 285.7 mg, sucrose - 2748.3 mg, titanium dioxide - 35.7 mg, xanthan gum - 3.8 mg, fruit flavoring - 35.7 mg, potassium sorbate - 20 mg, anhydrous citric acid - 4.2 mg, hypromellose phthalate - 152.1 mg, castor oil - 16.1 mg.

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

Description of the dosage form

Granules for the preparation of a suspension for oral administration in the form of a granular powder from white to light yellow in color, with a fruity aroma; When shaken with water, an opaque suspension of white to light yellow color is formed, with a fruity aroma.

pharmachologic effect

Antibacterial, bacteriostatic.

Pharmacokinetics

The drug is quickly absorbed into the gastrointestinal tract. Absolute bioavailability is about 50%. With repeated doses of the drug, no accumulation was detected, and the nature of metabolism in the human body did not change. Eating immediately before taking the drug increased the bioavailability of the drug by an average of 25%.

Clarithromycin can be taken before or with meals.

In in vitro studies, the binding of clarithromycin to plasma proteins was 70% at concentrations from 0.45 to 4.5 μg/ml. At a concentration of 45 μg/ml, binding decreases to 41%, probably as a result of saturation of binding sites. This is observed only at concentrations many times higher than the therapeutic value.

Healthy

When clarithromycin was prescribed at a dose of 250 mg 2 times a day, the maximum Css of clarithromycin and 14-hydroxyclarithromycin in plasma were reached after 2–3 days and were 1 and 0.6 μg/ml, respectively. T1/2 of the parent drug and its main metabolite were 3–4 and 5–6 hours, respectively. When clarithromycin was prescribed at a dose of 500 mg 2 times a day, the maximum Css of clarithromycin and 14-hydroxyclarithromycin in plasma were achieved after taking the 5th dose and amounted to on average 2.7–2.9 and 0.88–0.83 μg/ml, respectively. T1/2 of the parent drug and its main metabolite were 4.5–4.8 hours and 6.9–8.7 hours, respectively.

At steady state, the level of 14-hydroxyclarithromycin does not increase in proportion to clarithromycin doses, and T1/2 of clarithromycin and its main metabolite increase with increasing dose. The nonlinear nature of the pharmacokinetics of clarithromycin is associated with a decrease in the formation of 14-OH- and N-demethylated metabolites when using higher doses, which indicates the nonlinearity of the metabolism of clarithromycin when taking high doses. About 37.9% is excreted in the urine after taking 250 mg and 46% after taking 1200 mg of clarithromycin, through the intestines - about 40.2 and 29.1%, respectively.

Clarithromycin and its 14-OH metabolite are well distributed into tissues and body fluids. After oral administration of clarithromycin, its content in cerebrospinal fluid remains low (with normal BBB permeability of 1–2% of the level in blood serum). The content in tissues is usually several times higher than the content in blood serum.

The table provides examples of tissue and serum concentrations.

Concentrations (250 mg every 12 hours)

In patients with moderate and severe violation functional state of the liver, but with preserved kidney function, no dose adjustment of clarithromycin is required. Css in blood plasma and systemic clearance of clarithromycin do not differ between patients in this group and healthy patients. Css of 14-hydroxyclarithromycin in people with impaired liver function is lower than in healthy people.

Renal dysfunction

If renal function is impaired, the minimum and maximum levels of clarithromycin in the blood plasma, T1/2, AUC of clarithromycin and 14-OH metabolite increase. The elimination constant and urinary excretion decrease. The degree of changes in these parameters depends on the degree of renal dysfunction.

Elderly patients

In elderly patients, the level of clarithromycin and its 14-OH metabolite in the blood was higher, and elimination was slower than in the group of young people. It is believed that changes in pharmacokinetics in elderly patients are associated primarily with changes in creatinine clearance and renal function, and not with the age of the patients.

Patients with mycobacterial infections

Css of clarithromycin and 14-OH-clarithromycin in patients with HIV infection who received clarithromycin in usual doses (500 mg 2 times a day) were similar to those in healthy people. However, when clarithromycin is used in higher doses, which may be required to treat mycobacterial infections, antibiotic concentrations may be significantly higher than usual.

In patients with HIV infection taking clarithromycin at a dose of 1000 and 2000 mg/day in 2 divided doses, Css were usually 2–4 and 5–10 μg/ml, respectively. 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 concentrations and T1/2 duration when clarithromycin is prescribed at higher doses is consistent with the known nonlinearity of the pharmacokinetics of the drug.

Combination treatment with omeprazole

Clarithromycin 500 mg 3 times a day in combination with omeprazole at a dose of 40 mg/day increases T1/2 and AUC0-24 of omeprazole. In all patients receiving combination therapy, compared with those receiving omeprazole alone, there was an 89% increase in AUC0-24 and a 34% increase in T1/2 of omeprazole. For clarithromycin, Cmax, Cmin and AUC0-8 increased by 10, 27 and 15%, respectively, compared with data when clarithromycin alone was used without omeprazole. At steady state, clarithromycin concentrations in the gastric mucosa 6 hours after dosing in the group receiving the combination were 25 times higher than those in those receiving clarithromycin alone. Concentrations of clarithromycin in gastric tissue 6 hours after taking 2 drugs were 2 times higher than the data obtained in the group of patients receiving only clarithromycin.

Pharmacodynamics

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

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.

Clarithromycin is highly effective in vitro against Legionella pneumophila, Mycoplasma pneumoniae and Helicobacter (Campilobacter) pylori. Enterobacteriaceae and Pseudomonas, as well as other non-lactose-degrading gram-negative bacteria, are not sensitive to clarithromycin.

Clarithromycin has been shown to have an antibacterial effect against the following pathogens: aerobic gram-positive microorganisms - Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes; aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainftuenzae, Moraxella catarrhalis, Legionella pneumophila, Neisseria gonorrhoeae; other microorganisms - Mycoplasma pneumoniae, Chlamydia pneumoniae (TWAR), Chlamydia trachomatis; mycobacteria - Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum; Mycobacterium avium complex (MAC) - a complex including: Mycobacterium avium, Mycobacterium intracellulare.

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

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

Helicobacter pylori. The sensitivity of H. pylori to clarithromycin was studied on H. pylori isolates isolated from 104 patients before starting drug therapy. In 4 patients, strains of H. pylori were isolated that were resistant to clarithromycin, in 2 - strains with intermediate resistance, and in the remaining 98 patients, H. 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), Viridans group streptococci;
• aerobic gram-negative microorganisms - Bordetella pertussis, Pasteurella multocida;
• anaerobic gram-positive microorganisms - Clostridium perfringens, Peptococcus niger, Propionibacterium acnes;
• anaerobic gram-negative microorganisms - Bacteroides melaninogenicus;
• spirochetes - Borrelia burgdorferi, Treponema pallidum;
• campylobacter - Campylobacter jejuni.

The main metabolite of clarithromycin in the human body is the microbiologically active metabolite - 14-hydroxyclarithromycin (14-OH-clarithromycin). 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 H.influenzae, for which the effectiveness of the metabolite is 2 times higher. The parent substance and its major metabolite have either additive or synergistic effects against H. 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 MIC value of clarithromycin. The MIC value is determined by diluting the medium or diffusion into agar.

Laboratory tests give one of 3 results:

• resistant - we can assume that the infection cannot be treated with this drug;
• moderately sensitive - the therapeutic effect is ambiguous, and possibly increasing the dosage may lead to sensitivity;
• sensitive - the infection can be considered treatable with clarithromycin.

Indications for use

• lower respiratory tract infections (such as bronchitis, pneumonia);
• upper respiratory tract infections (such as pharyngitis, sinusitis);
• infections of the skin and soft tissues (such as folliculitis, inflammation of the subcutaneous tissue, erysipelas);
• mycobacterial infections caused by Mycobacterium avium and Mycobacterium intracellulare. Localized infections caused by Mycobacterium chelonae, Mycobacterium fortuitum and Mycobacterium kansasii;
• prevention of the spread of infection caused by Mycobacterium avium complex (MAC). HIV-infected patients with a CD4 lymphocyte count (T-helper lymphocytes) of no more than 100 per 1 mm3;
• to eliminate H. pylori and reduce the frequency of relapses of duodenal ulcers;
• odontogenic infections.

Contraindications for use

• hypersensitivity to macrolide drugs;
• simultaneous use of clarithromycin with the following drugs: astemizole, cisapride, pimozide, terfenadine, ergotamine, dihydroergotamine;
• porphyria;
• pregnancy;
• lactation period;
• children under 3 years of age.

With caution: impaired liver and kidney function.

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

Use during pregnancy and children

The safety of clarithromycin in pregnant and lactating women has not been studied. Clarithromycin is known to be excreted in breast milk. Therefore, the use of clarithromycin during pregnancy and lactation is recommended 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.

Side effects

The most common adverse events were from the gastrointestinal tract, incl. diarrhea, vomiting, abdominal pain and nausea. Other adverse reactions included headache, taste disturbances, and transient increases in liver enzymes.

Post-marketing experience

During treatment with clarithromycin, liver dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been reported infrequently. Hepatic dysfunction can be severe and is usually reversible. In very rare cases, deaths from liver failure have been reported, which were usually observed in the presence of serious concomitant diseases and/or concomitant use of other drugs.

Isolated cases of increased serum creatinine levels have been described, but their connection with the drug has not been established.

Allergic reactions have been reported with oral administration of clarithromycin, ranging from urticaria and minor rashes to anaphylaxis and Stevens-Johnson syndrome/toxic epidermal necrolysis.

There have been reports of transient CNS effects including dizziness, anxiety, insomnia, nightmares, tinnitus, confusion, disorientation, hallucinations, psychosis and depersonalization; their cause-and-effect relationship with the drug has not been established.

Cases of hearing loss have been reported during treatment with clarithromycin; after cessation of treatment, hearing was usually restored. There are also cases of disturbances in the sense of smell, which are usually combined with a perversion of taste.

Glossitis, stomatitis, oral thrush and discoloration of the tongue have been described during treatment with clarithromycin. There are known cases of tooth discoloration in patients treated with clarithromycin. These changes are usually reversible and can be corrected by your dentist.

Rare cases of hypoglycemia have been described, some of which were observed in patients receiving oral hypoglycemic agents or insulin.

Isolated cases of leukopenia and thrombocytopenia have been reported.

When treating with clarithromycin, as with other macrolides, prolongation of the QT interval, ventricular tachycardia and torsade de pointes (TdP) have been observed in rare cases.

Rare cases of pancreatitis and seizures have been described.

There are reports of the development of interstitial nephritis during treatment 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.

Children with suppressed immune systems

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

The main adverse events in patients taking clarithromycin orally at a dose of 1 g were nausea, vomiting, taste disturbance, abdominal pain, diarrhea, rash, 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 AST, ALT levels and decreased white blood cell and platelet counts. Fewer patients also experienced elevated blood urea nitrogen levels.

Drug interactions

Interaction with cytochrome P450

Clarithromycin is metabolized in the liver by the cytochrome P4503A isoenzyme (CYP3A). 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. The following drugs or classes are known or suspected to be metabolized by the same CYP3A isoenzyme: alprazolam, astemizole, carbamazepine, cilostazol, cisapride, cyclosporine, disopyramide, ergot alkaloids, lovastatin, methylprednisolone, midazolam, omeprazole, oral anticoagulants (e.g. warfarin), pimozide , quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, terfenadine, triazolam and vinblastine. Similar mechanisms of interaction, which are mediated by other cytochrome P450 isoenzymes, are characteristic of phenytoin, theophylline and valproic acid. In clinical studies, there was a small but statistically significant (p) difference when combining theophylline or carbamazepine with clarithromycin.

In clinical practice, the following CYP3A-mediated interactions have been reported with the use of erythromycin and/or clarithromycin.

When clarithromycin was combined with HMG-CoA reductase inhibitors, such as lovastatin and 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 caused disruption of the metabolism of terfenadine, which led to an increase in its plasma levels and was 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.

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

Interaction with other drugs. 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. It is a substrate for CYP3A and P-glycoprotein. Clarithromycin and other macrolides are inhibitors of CYP3A and P-glycoprotein. When colchicine and clarithromycin are coadministered, inhibition of P-glycoprotein and/or CYP3A may result in increased effects of colchicine. Patients should be closely monitored for symptoms of colchicine toxicity.

Interaction with antiretroviral drugs. Concomitant oral use of clarithromycin tablets with zidovudine in HIV-infected adults may result in a decrease in the Css of zidovudine. This interaction was not observed in HIV-infected children taking clarithromycin pediatric suspension with zidovudine or dideoxyinosine. In a pharmacokinetic study, the combined use of ritonavir at a dose of 200 mg every 8 hours and clarithromycin at a dose of 500 mg every 12 hours resulted in a significant suppression of the metabolism of clarithromycin. Cmax of clarithromycin when combined with ritonavir increased by 31%, Cmin by 182%, AUC by 77%.

Virtually complete inhibition of the formation of 14-hydroxyclarithromycin was observed. Given the high therapeutic index of clarithromycin, a dose reduction is not required in patients with normal renal function. However, in patients with impaired renal function, dose adjustment is advisable. In patients with Cl creatinine 30–60 ml/min, the dose of clarithromycin is reduced by 50%, and in patients with Cl creatinine

Dosage

Inside, regardless of food intake.

Typically, adults are prescribed 250 mg of clarithromycin 2 times a day. In more severe cases, the dose is increased to 500 mg 2 times a day. Typically, the duration of treatment is from 5–6 to 14 days.

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

For mycobacterial infections, 500 mg of the drug is prescribed 2 times a day.

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

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

For the prevention of infections caused by MAC. The recommended dose of clarithromycin for adults is 500 mg 2 times a day.

For odontogenic infections, the dose of clarithromycin is 250 mg 2 times a day for 5 days.

For eradication of H. pylori

Combination treatment with three drugs

Clarithromycin at a dose of 500 mg 2 times a day in combination with lansoprazole at a dose of 30 mg 2 times a day and amoxicillin at a dose of 1000 mg 2 times a day for 10 days.

Clarithromycin at a dose of 500 mg 2 times a day in combination with amoxicillin at a dose of 1000 mg 2 times a day and omeprazole at a dose of 20 mg/day for 7–10 days.

Combination treatment with two drugs

Clarithromycin at a dose of 500 mg 3 times a day in combination with omeprazole at a dose of 40 mg/day for 14 days, followed by omeprazole at a dose of 20–40 mg/day for the next 14 days.

Clarithromycin at a dose of 500 mg 3 times a day in combination with lansoprazole at a dose of 60 mg/day for 14 days. For complete healing of the ulcer, additional reduction in the acidity of gastric juice may be required.

Overdose

Symptoms: Taking a large dose of clarithromycin may cause symptoms of gastrointestinal disorders. 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: in case of overdose, 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 clarithromycin serum levels, which is also typical for other macrolide drugs.

Precautionary measures

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

Prescribe with caution against drugs metabolized by the liver.

In case of co-administration with warfarin or other indirect anticoagulants, PT must be monitored.

In children, it is preferable to use Klacid in powder dosage form for the preparation of an oral suspension of 125 mg/5 ml and 250 mg/5 ml.

ABBOTT LABORATORIES ABBOTT LABORATORIES LTD Famar L'Eil Abbott S.r.L. ABBOTT GmbH & Co.KG Abbott Laboratories Limited Abbott S.p.A. Abbott S.r.L. Abbott France Abbott Healthcare SAS Eisika Queenborough Limited

Country of origin

United Kingdom Italy United Kingdom UNITED STATES France

Product group

Antibacterial drugs

Macrolide antibiotic

Release forms

• 7 - blisters (1) - cardboard packs. 14 tablets in a pack of 42.3 g - plastic bottles with a volume of 60 ml (1) complete with a dosing spoon or syringe - cardboard packs. 5 - blisters (1) - cardboard packs. 7 - blisters (1) - cardboard packs. 70.7 g - plastic bottle with a volume of 100 ml - complete with a dosing spoon or syringe - cardboard packs 70.7 g - plastic bottles with a volume of 100 ml (1) complete with a dosing spoon or syringe - packs of cardboard Film-coated tablets 250 mg - 10 pcs per pack . Film-coated tablets 500 mg - 14 pcs per pack. Bottles (1) - cardboard packs

Description of the dosage form

• Lyophilisate for the preparation of a solution for infusion from white to almost white, with a slight aromatic odor Powder for the preparation of an oral suspension Powder for the preparation of an oral suspension in the form of granules of white or almost white color, with a fruity aroma; When shaken with water, a white or almost white opaque suspension with a fruity aroma is formed. Extended-release tablets, yellow, oval, film-coated. Extended-release tablets, yellow, oval, film-coated. Yellow, oval, film-coated tablets. Yellow, oval, film-coated tablets.

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 the high effectiveness of 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; other 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. Enterobacteriaceae, Pseudomonas spp., as well as other gram-negative bacteria that do not degrade lactose are not sensitive to clarithromycin. The production of beta-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 has an effect 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, Streptococcus (groups C, F, G), Streptococcus viridans group; aerobic gram-negative microorganisms: Bordetella pertussis, Pasteurella multocida; anaerobic gram-positive microorganisms: Clostridium 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. Susceptibility studies Quantitative methods, which require measuring the diameter of the zone of growth inhibition 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” - we can assume that the infection is treatable with clarithromycin.

Pharmacokinetics

Absorption and distribution After taking the drug orally, the absolute bioavailability is 50%. With repeated doses of the drug, no accumulation was detected. When taking Klacid, the SR at a dose of 500 mg 1 time / Cmax of clarithromycin and 14-hydroxyclarithromycin was 1.3 μg/ml and 0.48 μg/ml, respectively. When taking Klacid SR at a dose of 1 g (500 mg 2 each), the Cmax of clarithromycin and 14-hydroxyclarithromycin was 2.4 μg/ml and 0.67 μg/ml, respectively. When taking the drug in doses of 500 mg and 1 g/time, the time to reach Cmax in blood plasma is about 6 hours. Cmax of 14-hydroxyclarithromycin did not increase in proportion to the dose of clarithromycin, while T1/2 of both clarithromycin and its hydroxylated metabolite tended to increases with increasing dose. This nonlinear pharmacokinetics of clarithromycin, coupled with a decrease in the formation of 14-hydroxylated and N-demethylated products at high dosages, indicates a nonlinear metabolism of clarithromycin, which becomes more pronounced at high dosages. Clarithromycin binds to plasma proteins by 70% at concentrations from 0.45 to 4.5 μg/ml. At a concentration of 45 μg/ml, the degree of binding decreases to 41%, probably as a result of saturation of binding sites. This is observed only at concentrations many times higher than the therapeutic value. Clarithromycin and its metabolite 14-hydroxyclarithromycin quickly penetrate into body tissues and fluids. Limited data from trials involving small numbers of patients suggest that oral cerebrospinal fluid concentrations of clarithromycin are negligible. Concentrations in tissues are usually several times higher than in serum. Metabolism and elimination Clarithromycin is metabolized in the cytochrome P450 system with the participation of the CYP3A isoenzyme. The main metabolite of clarithromycin is the microbiologically active metabolite 14-hydroxyclarithromycin. With repeated doses of the drug, the nature of metabolism in the human body did not change. About 40% of the dose is excreted in the urine, about 30% through the intestines. When taking Klacid SR at a dose of 500 mg 1 time / T1/2 of clarithromycin and 14-hydroxyclarithromycin are 5.3 hours and 7.7 hours, respectively. When taking Klacid SR at a dose of 1 g (500 mg 2 times) T1/2 of clarithromycin and 14-hydroxyclarithromycin is 5.8 hours and 8.9 hours, respectively. Pharmacokinetics in special clinical cases In a comparative study, it was shown that with preserved renal function in patients with moderate and severe liver dysfunction, no dose adjustment is required. In patients with kidney disease, plasma concentrations of T1/2, Cmax and Cmin of clarithromycin and 14-hydroxyclarithromycin were higher than in patients with normal renal function. In patients with impaired renal function, the AUC was higher, and the elimination constant and renal excretion were lower. The degree of these differences correlated with the severity of kidney disease: the more severe

Special conditions

Long-term use of clarithromycin, like other antibiotics, can provoke colonization with an increase in the number of resistant bacteria and fungi. If a secondary infection occurs, adequate therapy should be prescribed. When treated with almost all antibacterial agents, cases of pseudomembranous colitis have been described, the severity of which can vary from mild to life-threatening. One of the symptoms of pseudomembranous colitis is diarrhea caused by Clostridium difficile. Therefore, when diarrhea occurs after prescribing antibacterial agents, the possibility of such a disease should be taken into account. After a course of antibiotic therapy, careful medical monitoring of the patient is necessary. Cases of the development of pseudomembranous colitis 2 months after taking antibiotics have been described. It is possible to develop cross-resistance to clarithromycin and other macrolide antibiotics, as well as lincomycin and clindamycin. In the presence of chronic liver diseases, it is necessary to regularly monitor serum enzymes. In case of co-administration with warfarin or other indirect anticoagulants, it is necessary to monitor the prothrombin time.

Compound

• 5 ml of ready-made suspension. clarithromycin 125 mg 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. clarithromycin 250 mg/5ml 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. clarithromycin 500 mg Excipients: lactobionic acid, sodium hydroxide 4%. clarithromycin 500 mg Excipients: anhydrous citric acid, sodium alginate, sodium calcium alginate, lactose, povidone K30, talc, stearic acid, magnesium stearate. Film shell composition: hypromellose, macrogol 400, macrogol 8000, titanium dioxide, quinoline yellow dye (E104), sorbic acid clarithromycin 500 mg Excipients: anhydrous citric acid, sodium alginate, sodium calcium alginate, lactose, povidone K30, talc, stearic acid , magnesium stearate. Film shell composition: hypromellose, macrogol 400, macrogol 8000, titanium dioxide, quinoline yellow dye (E104), sorbic acid. clarithromycin 500 mg 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).

Klacid indications for use

• - infections of the lower respiratory tract (bronchitis, pneumonia); - upper respiratory tract infections (pharyngitis, sinusitis); - otitis; - 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 mm3; - odontogenic infections.

Klacid contraindications

• - severe renal failure (creatinine clearance less than 30 ml/min); - simultaneous use of clarithromycin with the following drugs: astemizole, cisapride, pimozide, terfenadine, ergotamine, dihydroergotamine; - simultaneous use with the following drugs: alprazolam, midazolam, triazolam (oral dosage forms); - children under 18 years of age (efficacy and safety have not been established); - porphyria; - lactose intolerance, lactase deficiency, glucose-galactose malabsorption; - increased sensitivity to macrolide antibiotics. The drug should be prescribed with caution in cases of impaired liver and kidney function, myasthenia gravis (possible increased symptoms), and concomitant use with drugs that are metabolized by the liver.

Klacid dosage

• 0.5 g 0.5 g 125 mg/5 ml 250 mg 250 mg/5 ml 250 mg/5 ml 500 mg

Klacid side effects

• From the cardiovascular system: rarely - ventricular arrhythmia, incl. pirouette type, ventricular flutter and fibrillation, increased QT interval on the ECG. From the digestive system: often - dyspepsia, nausea, abdominal pain, vomiting, diarrhea, gastralgia, acute pancreatitis, glossitis, stomatitis, oral candidiasis, discoloration of the tongue and teeth; rarely - pseudomembranous enterocolitis, liver dysfunction, incl. increased activity of liver enzymes, hepatic cell and/or cholestatic jaundice. In very rare cases, cases of liver failure with a fatal outcome have been reported, mainly due to severe concomitant diseases and/or concomitant drug therapy. From the side of the central nervous system: often - headache; rarely - dizziness, anxiety, insomnia, nightmares, ringing in the ears, depersonalization, hallucinations, convulsions, mental disorders, confusion, disorientation, depression. From the musculoskeletal system: myalgia. From the urinary system: interstitial nephritis. From the senses: often - distortion or loss of taste; possible - deafness, change in sense of smell. Allergic reactions: anaphylactic reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, skin flushing, itchy skin, rash. From the hematopoietic system: leukopenia, thrombocytopenia. From laboratory parameters: increase in creatinine content in the blood;

Drug interactions

The use of the following drugs with clarithromycin is contraindicated due to the potential for serious side effects. Cisapride and pimozide When used together, it is possible to increase the concentration of cisapride, increase the QT interval, and cause cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, and ventricular tachycardia of the torsade de pointes type. Terfenadine and astemizole When used together, it is possible to increase the concentration of terfenadine/astemizole in the blood, the appearance of cardiac arrhythmias, an increase in the QT interval, the development of ventricular tachycardia, ventricular fibrillation and ventricular tachycardia of the pirouette type. Ergotamine/dihydroergotamine When used together, the following effects associated with acute poisoning with drugs of the ergotamine group are possible: vascular spasm, ischemia of the limbs and other tissues, including the central nervous system. Effect of other drugs on clarithromycin

Overdose

: Taking a large dose of clarithromycin may cause gastrointestinal symptoms. One patient with a history of bipolar disorder developed mental status changes, paranoid behavior, hypokalemia, and hypoxemia after taking clarithromycin 8 g.

Storage conditions

• keep away from children
• store in a place protected from light

Information provided