Clarithromycin dosage for adults. "Clarithromycin": side effects, instructions for use, contraindications

Clarithromycin ® is a semi-synthetic fourteen-membered macrolide derived from erythromycin and has a special lactone ring structure that allows the antibiotic to be stable in an acidic environment.

Resistance of clarithromycin ® to action gastric juice one hundred times higher than that of erythromycin. Antimicrobial used in the first line of Helicobacter pylori eradication.

Erythromycin significantly loses to clarithromycin ® in terms of pharmacokinetic and pharmacological properties. Clarithromycin ® was synthesized in the 1970s by Taisho Pharmaceutical in Japan.

Clarithromycin ® : instructions for use (tablets of 250 mg and 500 mg)

Clarithromycin Teva ® is a representative of a group of antibiotics of semi-synthetic fourteen-membered macrolides.

It inhibits protein biosynthesis in the cell by reversibly binding to the 50-S ribosome subunits. Good bioavailability and the ability to create high concentrations in various tissues and organs became possible due to changes in the drug molecule.

Long T1 / 2 allows you to prescribe the drug twice a day. Maximum concentration medicinal product achieved in plasma, observed after two to three hours. When taken orally, the drug is absorbed fairly quickly.

The broad spectrum of antimicrobial activity includes gram+ and gram-pathogens as well as intracellular and extracellular pathogens. Macrolide antibiotic is active against aerobes and anaerobes. Sensitive to the drug:

• borrelia burgdorferi;
• gonococcus;
• golden staphylococcus aureus;
• jeuni campylobacter;
• whooping cough;
• corynebacteria;
• legionella pneumophila;
• listeria monocytogenes;
• meningococcus;
• mycobacterium kansashi;
• mycoplasma pneumonia;
• moraxella catharalis;
• sticks: ducrey, pfeiffer, hansen;
• pasteurella multicide;
• propionibacterium acne;
• staphylococci;
• streptococcus agalactia;
• toxoplasma;
• ureaplasma urealiticum;
• helicobacter pylori;
• chlamydia trachomatis;
• chlamydophila pneumonia;
• as well as some anaerobic cultures, which include eubacteria, peptococci, propionic acid bacteria, clostridium perfringens.

Enterobacteria, Pseudomonas and other gram pathogens that are not able to decompose lactose are resistant to the macrolide antibiotic. Beta-lactamases do not reduce the effectiveness of the drug.

Practitioners prefer clarithromycin ® over erythromycin because the former is better absorbed from the gastrointestinal tract and does not break down at low pH values. The latter property reduces the likelihood of adverse drug reactions from the gastrointestinal tract. Clarithromycin Teva ® has a pronounced antimicrobial activity against intracellular microorganisms.

Another advantage of clarithromycin ® is that the antibiotic is able to reduce inflammation. This property allows you to speed up recovery and get rid of symptoms in the shortest possible time.

Injection administration is prescribed for adults at a daily dosage of 1 g, divided into two injections. Intravenous drip administration continues for one hour. With mycobacterial infections, the dosage is doubled. For patients with impaired renal function, the dose of antibiotic is reduced by fifty percent. Jet infusion of clarithromycin ® is not used.

Clarithromycin Teva ® is prescribed with caution against the background of drugs that are metabolized in the liver. Sustained-release antibiotic is not prescribed to patients with severe renal insufficiency. These patients are indicated for immediate release clarithromycin®.

It must be borne in mind that there is a risk of developing cross-resistance with other macrolide antibiotics. Prolonged antibiotic therapy can cause superinfection.

The official instructions say that clarithromycin ® is not allowed to be combined with the following drugs:

• Astemizolum, Terfenadinum and Pimozidum (simultaneous use contributes to the lengthening of the QT interval and cardiac arrhythmia);
• Dihydroergotaminum (possible development of ergotoxicity);
• Lovastatinum and Simvastatinum (if taken at the same time, the risk of rhabdomyolysis increases).

In case of an overdose, there are violations of the gastrointestinal tract, as well as headache and confusion. Gastric lavage helps to eliminate the symptoms. Hemodialysis is not performed.

Pharmacological group

Antibiotics - macrolides.

Prescription for clarithromycin ® in Latin

Rp.: Clarithromycini 0.5
D.t.d. No. 14.
S. 1 tablet 2 times a day.

Release form Clarithromycin ®

Clarithromycin ® is available for sale in the following dosage forms:

• granules;
• lyophilizate:
• powder for suspension.

The antibiotic is also available in the form of tablets of two types: fast release and prolonged release.

Photo of the packaging of clarithromycin ® 500 mg tablets

One plastic container contains ten clarithromycin ® film-coated tablets, each containing 250 mg or 500 mg of the active ingredient.

Clarithromycin ® : indications for use and contraindications

The antibiotic is used in clinical practice for the eradication of infections provoked by strains sensitive to the action of clarithromycin.

LS shown at the following diseases bacterial etiology:

• infectious processes localized in the respiratory tract (, pharyngitis);
• infectious lesions of the skin and subcutaneous fat (folliculitis, Baker's creeping);
• odontogenic inflammatory diseases;
• in patients with human immunodeficiency virus - common lesions with the Mycobacterium avium complex ;
• mycobacterial infections provoked by mycobacterium avium, as well as localized infections caused by mycobacterium fortuitum;
• elimination in patients with peptic ulcer 12 duodenal ulcer with a decrease in the production of hydrochloric acid.

Clarithromycin Teva ® is contraindicated in hypersensitivity to macrolides, with pathological changes kidney function, with porphyria, as well as patients with the syndrome extended interval QT and pirouette blinking.

Clarithromycin ® is not prescribed for pregnant (first trimester) and lactating women. Conducting antibiotic therapy during pregnancy (2nd and 3rd trimesters) is permissible after a thorough assessment of the benefit / risk ratio. Breast-feeding excluded during antibiotic therapy.

The injection method of administering the drug is not suitable for persons under 18 years of age. The tablet form is not assigned to childhood(up to 12 years).

Dosage of Clarithromycin®

Tablets when taken orally are not chewed and washed down with a small amount of liquid. Foods do not affect bioavailability medicinal product therefore, clarithromycin ® can be taken before or after meals.

The recommended dosage for adults and children over twelve years of age is 250 mg every twelve hours. In severe infections, the dosage is doubled. The course of treatment depends on the severity of the infectious process and takes from six days to two weeks.

Need for dosage adjustments in the treatment of patients old age no. The exception is cases of severe kidney failure.

Suspension for children

The daily dosage is calculated based on the body weight of the child. The maximum daily dosage for non-mycobacterial infections in children is 500 milligrams twice daily. The duration of therapy (an average of five to ten days) depends on the severity of the infectious process and the strain of the pathogen.

Suspension intake does not depend on food intake. Parents of young children should take into account that the granules are bitter in taste and the child should not chew them. Clarithromycin ® instructions contain information that drugs can be taken with milk. Clarithromycin ® suspension has a pleasant taste, as it contains banana and orange flavors.

For the treatment of mycobacterial infections (Mycobacterium), the recommended dosage is from 7.5 to 15 milligrams per kg of body weight twice a day, taking into account the individual clinical assessment of the patient's condition.
Antibiotic therapy continues until a visible therapeutic effect occurs.

The tables show the dosage of the antibiotic depending on body weight:

Side effects of Clarithromycin ®

Allergy: skin rash, irritation, burning, tingling, anaphylactic reactions.

Invasions and infectious lesions: thrush in the mouth, various vaginal infections, catarrh of the stomach and intestines, erysipelas.

Violations by of cardio-vascular system: heart failure, increased ventricular contractions, long QT syndrome, vasodilation, hemorrhage.

From the side immune system: hypersensitivity, pseudo-allergic reactions and anaphylaxis.

From the blood and lymphatic system: a decrease in the number of leukocytes, neutrophils, an increase in the number of eosinophils, a decrease in the level of leukocytes, a decrease in the number of platelets.

From the side of metabolic processes and nutrition: loss of appetite, decreased blood glucose concentration, anorexia.

From the side nervous system: vertigo, anxiety, sleep disturbances, nightmares, disorientation, hallucinatory states, self-perception disorder, sensation of extraneous sounds in the ears without external auditory stimuli.

From the sense organs: violation of taste perception, deafness, passing after the abolition of the antibiotic.

From the gastrointestinal tract: dyspepsia, antibiotic-associated diarrhea, glossitis, elevated liver transaminases, intrahepatic cholestasis.

From the side of the central nervous system: distortion of taste sensations, parorexia, general weakness of the body, convulsions, impaired olfactory function, paresthesia.

In patients with impaired immune function (for example, acquired immune deficiency syndrome), clarithromycin ® causes side effects, which can not always be distinguished from the symptoms of concomitant diseases.

Compatibility of Clarithromycin ® with alcohol

It is not recommended to combine antibiotics and alcohol. Alcohol intake reduces the effectiveness of ongoing antimicrobial therapy, increases the load on the liver and increases the risk of developing cholestasis (bile stasis).

The use of clarithromycin ® during pregnancy and lactation

Macrolide preparations have low toxicity and do not exhibit teratogenic effects. If necessary, clarithromycin during pregnancy can be used after consulting a doctor. In the first trimester of pregnancy, the antibiotic can be used only for health reasons; if there is an alternative, it is recommended to replace it with another macrolide. (from 370 to 520 rubles), Fromilid Uno ® (from 220 to 310 rubles), (from 334 to 470 rubles), Clarithrosin ® (from 140 to 190 rubles) and Ecozitrin ® (from 340 to 480 rubles. )

There are contraindications. Please consult your doctor before taking.

Commercial names abroad (abroad) - Abbic, Biaxin, Biclar, Binoclar, Celex, Centromicina, Clacee, Claribid, Claripen, Clarem, Claridar, Clariwin, Crixan, Claritt, Clarac, Clarihexal, Clarisol, Clatic, Hamun, Heliclar, Infex , Klaram, Klaricid, Klarmyn, Kofron, Lagur, Lekoklar, Mabicrol, Maclar, Mavid, Monocid, Naxy, Resclar, Urclar, Vikrol, Zeclar.

Antibacterial agents that are not antibiotics.

You can ask a question or leave a review about the medicine (please do not forget to indicate the name of the drug in the text of the message).

Preparations containing Clarithromycin (Clarithromycin, ATC code (ATC) J01FA09):

Klacid (original Clarithromycin) - official instructions for use. Prescription drug, information intended for healthcare professionals only!

Clinico-pharmacological group:

macrolide antibiotic

pharmachologic effect

Semi-synthetic macrolide antibiotic. 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 efficacy 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, 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 decompose lactose, are insensitive to clarithromycin.

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

The susceptibility of Helicobacter pylori to clarithromycin was studied on isolates of Helicobacter pylori isolated from 104 patients prior to initiation of drug therapy. Clarithromycin-resistant strains of Helicobacter pylori were isolated in 4 patients, strains with intermediate resistance were isolated in 2 patients, and Helicobacter pylori isolates were sensitive to clarithromycin in the remaining 98 patients.

Clarithromycin is active in vitro and against most strains of the following microorganisms (however, the safety and efficacy of using clarithromycin in clinical practice has not been confirmed clinical research and 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: Clostridium perfringens, Peptococcus niger, Propionibacterium acnes; anaerobic gram-negative microorganisms: Bacteroides melaninogenicus; Borrelia burgdorferi, Treponema pallidum, Campylobacter jejuni.

The main metabolite of clarithromycin in humans 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 in relation to most microorganisms. The exception is Naemophilus influenzae, for which the effectiveness of the metabolite is 2 times higher. The parent substance and its major metabolite have either an additive or synergistic effect on Haemophilus influenzae in vitro and in vivo, depending on the bacterial culture.

Sensitivity studies

Quantitative methods that require measuring the diameter of the zone of inhibition of growth of microorganisms provide the most accurate estimates of the sensitivity of bacteria to antimicrobial agents. One recommended susceptibility test uses discs impregnated with 15 micrograms 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 the method of dilution of the medium or diffusion into agar. Laboratory tests give one of three results: 1) "resistant" - it can be considered that the infection is not amenable to treatment with this drug; 2) "medium sensitive" - therapeutic effect is ambiguous, and it is possible that increasing the dosage may lead to sensitivity; 3) "sensitive" - ​​it can be considered that the infection is treatable with clarithromycin.

Pharmacokinetics

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

The bioavailability and pharmacokinetics of clarithromycin suspension have been 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 exceeded. Eating somewhat delayed the absorption of clarithromycin suspension, but did not affect the overall bioavailability of the drug.

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

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

At healthy people serum concentrations peaked within 2 hours after ingestion. Cssmax 14-hydroxyclarithromycin is about 0.6 μg / ml. When prescribing clarithromycin at a dose of 500 mg every 12 hours, Cssmax of 14-hydroxyclarithromycin is slightly higher (up to 1 μg / ml). When using both doses, Cssmax of the metabolite is usually achieved within 2-3 days.

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

Metabolism and excretion

Clarithromycin is metabolized in the liver by the action of the CYP3A isoenzyme with the formation of a microbiologically active metabolite 14-hydroxyclarithromycin.

T1 / 2 of clarithromycin when taking a pediatric suspension (after eating) was 3.7 hours. When using a suspension of clarithromycin 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 using clarithromycin at a dose of 250 mg every 12 hours, approximately 20% of the dose is excreted in the urine unchanged. When using clarithromycin at a dose of 500 mg every 12 hours, approximately 30% of the dose is excreted in the urine unchanged. The renal clearance of clarithromycin is not significantly dose dependent and approaches the normal glomerular filtration rate. The main metabolite found in the urine is 14-hydroxyclarithromycin, which accounts for 10-15% of the dose (250 mg or 500 mg every 12 hours).

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

In children requiring oral antibiotic treatment, clarithromycin has a high bioavailability. At the same time, its pharmacokinetic profile was similar to that in adults taking the same suspension. The drug is rapidly 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 who received repeated clarithromycin at a dose of 500 mg, in a comparative study, an increase in plasma levels of the drug and a slowdown in elimination were found compared with those in young healthy people. However, no difference was found between the two groups when adjustment for creatinine clearance was made. 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), the average concentrations of clarithromycin and 14-hydroxyclarithromycin in the middle ear were 2.53 and 1.27 mcg/g. The concentrations of the drug and its metabolite were 2 times higher than their serum levels.

In patients with impaired liver function, Css 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 people.

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 of these parameters correlated with the degree of renal insufficiency: with a more pronounced impairment of kidney function, the differences were more significant.

In adult patients with HIV infection who received the drug at usual doses, Css of clarithromycin and its metabolite were similar to those in healthy people. However, when using clarithromycin at 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 who took clarithromycin at a dose of 15-30 mg / kg / day in 2 doses, the equilibrium Cmax values ​​​​usually ranged from 8 to 20 mcg / ml. However, in children with HIV infection who received a suspension of clarithromycin at a dose of 30 mcg / kg / day in 2 doses, Cmax reached 23 mcg / ml. When using the drug in higher doses, an elongation of T1 / 2 was observed compared with that in healthy people who received clarithromycin at usual doses. The increase in plasma concentration and duration of T1 / 2 with the appointment of clarithromycin at higher doses is consistent with the known non-linearity of the pharmacokinetics of the drug.

Indications for use of the drug KLATSID®

• lower body infections respiratory tract(bronchitis, pneumonia);
• infections of the upper respiratory tract (pharyngitis, sinusitis);
• otitis;
• skin and soft tissue infections (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 recurrence 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) not more than 100 per 1 mm3;
• odontogenic infections.

Dosage regimen for oral administration:

Tablets:

The drug is taken orally, regardless of the meal.

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

Klacid® SR (sustained release) is prescribed 500 mg (1 tablet) 1 time per day. In severe infections, the dose is increased to 1 g (2 tablets) 1 time per day.

The usual duration of treatment is 5-14 days. The exceptions are community-acquired pneumonia and sinusitis, which require treatment within 6-14 days.

Klacid® SR tablets should be taken with meals, swallowed whole, not crushed or chewed.

Patients with CC less than 30 ml / min are prescribed half the usual dose of clarithromycin, i.e. 250 mg once daily or, for more severe infections, 250 mg twice daily. Treatment of such patients continue no more than 14 days.

With mycobacterial infections, 500 mg is prescribed 2 times a day.

For widespread MAC infections in AIDS patients, treatment should be continued as long as there is clinical and microbiological evidence of benefit. Clarithromycin should be given in combination with other antimicrobials.

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

For the prevention of MAC infections, the recommended adult dose of clarithromycin is 500 mg twice daily.

For odontogenic infections, the dose of clarithromycin is 250 mg twice daily for 5 days.

For Helicobacter pylori eradication:

Combined treatment with three drugs:

• clarithromycin 500 mg twice daily + lansoprazole 30 mg twice daily + amoxicillin 1000 mg twice daily for 10 days;
• clarithromycin 500 mg 2 times a day + omeprazole 20 mg per day + amoxicillin 1000 mg 2 times a day for 7-10 days.

Combined treatment with two drugs:

• clarithromycin 500 mg 3 times a day + omeprazole 40 mg per day for 14 days with the appointment within the next 14 days of omeprazole at a dose of 20-40 mg / day;
• clarithromycin 500 mg 3 times daily + lansoprazole 60 mg daily 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 finished suspension should be taken orally, regardless of the meal (you can with milk).

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

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

The recommended daily dose of clarithromycin suspension for non-mycobacterial infections in children is 7.5 mg/kg twice daily. The maximum dose is 500 mg 2 times a day. The usual duration of treatment is 5-7 days, depending on the pathogen and the severity of the patient's condition. Shake the vial well before each use.

*in children with body weight<8 кг дозу подбирают по массе тела (примерно 7.5 мг/кг 2)

In children with CC<30 мл/мин дозу кларитромицина следует снизить вдвое: до 250 мг 1 раз в сутки или 250 мг 2 раза в сутки при более тяжелых инфекциях. В таких случаях курс лечения не должен превышать 14 дней.

In 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 for as long as the clinical effect persists. It may be useful to attach other antimycobacterial drugs.

Doses are in standard teaspoons (5 ml) twice a day.

*in children with body weight<8 кг дозу подбирают по массе тела (15-30 мг/кг/сутки)

Dosing regimen of the intravenous form of the drug:

Data on the dosage of the drug Klacid® for children is not available.

It is forbidden to / m and bolus administration of the drug.

Patients with mycobacterial infections

There are no data on the use of IV clarithromycin in immunosuppressed patients. In HIV-infected patients, clarithromycin was administered orally.

In localized and disseminated mycobacterial infections caused by Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium kansasii, the recommended dose of clarithromycin for adults is 1 g per day in 2 divided doses. IV therapy in severe patients is carried out within 2 to 5 days with a possible subsequent transition, at the discretion of the doctor, to taking clarithromycin orally.

In patients with impaired renal function and CC less than 30 ml / min, the dose of clarithromycin should be reduced by half of the normal recommended dose.

Solution preparation rules

1) Add 10 ml of sterile water for injection to the 500 mg vial of lyophilisate. It is recommended to use only sterile water for injection, as any other solvent may cause precipitation. Do not use solvents containing preservatives or inorganic salts.

The reconstituted solution of the drug, obtained as described above, contains a sufficient amount of preservative and has a concentration of 50 mg/ml clarithromycin. The solution is stable for 48 hours at 5°C or 24 hours at 25°C. The reconstituted solution of the drug should be used immediately after its preparation. If the drug is not used immediately after receiving its reconstituted solution, it is recommended to store it for no more than 24 hours at a temperature of 2 ° to 8 ° C under aseptic conditions.

2) Before administration, the prepared solution of the drug (500 mg in 10 ml of water for injection) must be added to at least 250 ml of one of the following solvents for intravenous administration: 5% glucose solution in Ringer's lactate solution, 5% glucose solution , Ringer's lactate solution, 5% glucose dextrose solution in 0.3% sodium chloride solution, Normosol-M solution in 5% glucose solution, Normosol-R solution in 5% glucose solution, 5% glucose solution in 0.45% sodium chloride solution, 0.9% sodium chloride solution.

The physical and chemical parameters of the solution during storage for 48 hours at a temperature of 5°C or 6 hours at a temperature of 25°C do not change. However, the resulting solution of the drug is recommended to be used immediately after its preparation. If the resulting solution cannot be used immediately, it should be stored under aseptic conditions. The drug solution remains stable for 24 hours of storage at a temperature of 2° to 5°C. After this period, further storage and use of clarithromycin IV solution is not recommended.

The solution should not be mixed with any medicinal products or diluents unless their physical or chemical compatibility with IV clarithromycin has been first established.

Side effect

The most common adverse events from the digestive system: diarrhea, vomiting, abdominal pain, nausea. Extremely rarely observed pseudomembranous enterocolitis. Other adverse reactions included headache, taste disturbance, and transient elevations in liver enzymes. As with the use of other antibiotics of the macrolide group, the development of resistance of microorganisms may be noted.

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

Post-marketing experience

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

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

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

On the part of the senses: hearing loss (after the treatment was stopped, hearing was usually restored), a violation of smell, usually combined with a perversion of taste.

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

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

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

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

Children with suppressed immunity

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

The main adverse events in patients taking clarithromycin 1 g orally were nausea, vomiting, taste perversion, abdominal pain, diarrhea, rash, abdominal distension, headache, hearing loss, constipation, elevated AST and ALT levels. Dyspnea, insomnia, and dry mouth have also been reported less frequently.

In this group of patients with suppressed immunity, significant deviations of laboratory parameters from the normative values ​​in specific tests (a sharp increase or decrease) were recorded. Based on this, approximately 2-3% of patients taking oral clarithromycin at a dose of 1 g / day had significant laboratory abnormalities, such as an increase in the level of AST, ALT and a decrease in the number of leukocytes and platelets. In a smaller number of patients, an increase in the level of blood urea nitrogen was also observed.

In a limited number of pediatric AIDS patients, 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 the normative values ​​(a sharp increase or decrease) were recorded. Based on these criteria, one child with AIDS who received clarithromycin at a dose of<15 мг/кг/сутки, отмечено значительное повышение уровня общего билирубина; среди пациентов, принимавших кларитромицин в дозе 15-25 мг/кг/сутки, было зарегистрировано по одному случаю значительного повышения уровней АЛТ, остаточного азота мочевины и снижения числа тромбоцитов. У пациентов, получавших кларитромицин в максимальной дозе (≥25 мг/кг/сутки), значительных изменений указанных лабораторных параметров не выявлено.

Contraindications to the use of the drug KLATSID®

• severe liver dysfunction;
• severe renal impairment (KK<30 мл/мин);
• porphyria;
• simultaneous use with astemizole, cisapride, pimozide, terfenadine, ergotamine, dihydroergotamine;
• pregnancy;
• lactation period (breastfeeding);
• children's age up to 3 years (for the dosage form in the form of tablets);
• hypersensitivity to macrolide antibiotics.

With caution, the drug should be prescribed to patients with impaired liver and kidney function.

The use of the drug KLATSID® during pregnancy and lactation

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

Clarithromycin is known to be excreted in breast milk.

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

Application for violations of liver function

The use of the drug is contraindicated in severe violations of liver function, porphyria.

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

Application for violations of kidney function

The use of the drug is contraindicated in severe violations of kidney function (QC<30 мл/мин).

With caution, the drug should be prescribed to patients with impaired renal function.

special instructions

Clarithromycin is excreted mainly 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 conduct regular monitoring of blood serum enzymes.

Caution should be observed in the treatment of clarithromycin in patients with moderate to severe renal insufficiency.

Cases of toxicity of colchicine in combination with clarithromycin have been described in clinical practice, especially in the elderly. Some of them were observed at patients with a renal failure; Several deaths have been reported in these patients.

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

Be wary appoint against the background of drugs metabolized by the liver.

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

Overdose

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

Treatment: 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 serum, which is typical for other drugs of the macrolide group.

drug interaction

Clarithromycin is metabolized in the liver by the CYP3A isoenzyme. This mechanism determines many interactions with other drugs. Clarithromycin may inhibit the biotransformation of other drugs by this system, which may lead to an increase in their serum levels.

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

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

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

With the simultaneous use of clarithromycin with inhibitors of HMG-CoA reductase (lovastatin, simvastatin), rhabdomyolysis developed in rare cases.

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

Macrolides cause a violation 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 ventricular tachycardia of the "pirouette" type. In one study in 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 of terfenadine and prolongation of the QT interval, which was not accompanied by any clinical effects.

In clinical practice, cases of ventricular tachycardia of the "pirouette" type have been reported with the combination of clarithromycin with quinidine or disopyramide. During treatment with clarithromycin, serum levels of these drugs should be monitored.

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

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

Colchicine is a substrate for CYP3A and P-glycoprotein. Clarithromycin and other macrolides are inhibitors of CYP3A and P-glycoprotein. With the simultaneous appointment of colchicine and clarithromycin, inhibition of P-glycoprotein and / or CYP3A can lead to an increase in the action of colchicine. Patients should be carefully monitored for symptoms of toxic effects of colchicine.

Simultaneous oral administration of clarithromycin tablets with zidovudine in HIV-infected adults may lead to a decrease in the steady-state concentrations of zidovudine. No such interaction has been observed in HIV-infected children receiving clarithromycin 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 in combination with ritonavir increased by 31%, Cmin - by 182%, AUC - by 77%. Virtually complete inhibition of the formation of 14-hydroxyclarithromycin was noted. Given the high therapeutic index of clarithromycin, dose reduction is not required in patients with normal renal function. However, in patients with impaired renal function, dose adjustment is reasonable. In patients with CC = 30-60 ml / min, the dose of clarithromycin is reduced by 50%, and in patients with CC<30 мл/мин - на 75%. В дозах >Clarithromycin 1 g/day should not be used in combination with ritonavir.

Terms of dispensing from pharmacies

The drug is dispensed by prescription.

Terms and conditions of storage

List B. The drug in the form of tablets should be stored out of the reach of children, protected from light at a temperature not exceeding 25 ° C. Shelf life - 5 years.

The drug in the form of a powder for oral suspension should be stored out of the reach of children, protected from light at a temperature not exceeding 30 ° C. Shelf life - 2 years.

The finished suspension can be stored for 14 days at room temperature.

Thanks

The site provides reference information for informational purposes only. Diagnosis and treatment of diseases should be carried out under the supervision of a specialist. All drugs have contraindications. Expert advice is required!

Clarithromycin and macrolides

So, clarithromycin belongs to the semi-synthetic macrolides of the third generation.
What distinguishes this group of antibiotics is that they can also destroy those microbes that settle in tissue cells, so conventional antibiotics simply cannot get them there. These microbes include certain types of bacteria and bacilli that cause severe diseases of the internal organs.

How does clarithromycin affect the pathogen?

What diseases is clarithromycin effective for?

You can safely take clarithromycin and treat your children with it (on prescription of course, of course). Clarithromycin effectively fights most microbes that cause inflammation of the respiratory system. In addition, clarithromycin is convenient to use, because it can be taken only once a day. It is very quickly absorbed into the blood, but it also does not stay in the blood for a long time. From there, clarithromycin enters the soft tissues and accumulates there in optimal amounts. In addition, the use of clarithromycin is quite safe. It is impossible to talk about the complete absence of side effects from taking this drug, but there are much fewer of them than with other antibiotics.

Another significant advantage of clarithromycin over other antibiotics is that it practically does not cause allergic reactions. This is especially important for those patients who are allergic to penicillins. Clarithromycin has passed a lot of clinical trials and they all proved the effectiveness and safety of this drug.

By the way, clarithromycin is able to cope even with such a formidable disease as tuberculosis. Mycobacterium tuberculosis is sensitive to this drug, so it is included in a number of drugs used to treat even chronic forms of tuberculosis. In some countries, clarithromycin is used in government tuberculosis control programs. And clarithromycin shows good results. For example, in Ukraine, the cure rate for tuberculosis has increased by fifteen percent due to the introduction of clarithromycin into the course of treatment.

Clarithromycin is also effective against chlamydia, against legionella and other very difficult infections to cure.

What can we say about staphylococci, streptococci and other harmful microbes. Clarithromycin is prescribed even in such severe cases as the treatment of infections in patients with AIDS.
And with the help of clarithromycin, you can get rid of the very microbe that causes the development of stomach and intestinal ulcers. This microbe is called helicobacter pylori, and it is not at all easy to expel it from the body.

Reviews

I often get sick accompanied by severe sore throats, a doctor came, you have a virus and prescribes Ingavirin, I explain last year I was also prescribed this drug, it didn’t even help me close, I lost time and the antibiotics that were on my table said to throw it away. Then he went back to antibiotics. They helped. I ask, besides Ingavirin, do you know any medications? Yes, he says you have a secondary infection and you need to take antibiotics. Ingavirin should be sold, there is no need to cure people. I'm shocked.

Excellent antibiotic after taking 1 tablet felt better

Good, there was a sore throat, all the tonsils were in bloom, traffic jams, the temperature was under 40. After the first dose of 2 tablets, after a couple of hours the temperature went down, even the plaque became less. With my chronic sore throat, the best helper.

Good afternoon! They prescribed this drug to me, after the very first pill there was a terrible taste of bitterness in my mouth, which does not go away, I drink and eat, and after 5 minutes bitterness again. After the second tablet, a headache and dizziness appeared. During my life, unfortunately, I drank a lot of drugs, but this never happened. I could not stand it and called the doctor to replace the drug with another one. Not a cure, but a pain. It looks like it hasn't been tested. There are a lot of bad reviews on the internet like mine...

I take the 5th day 500mg in 12 hours! I don’t observe side effects, although a friend had changes in taste perception and some kind of panic and he refused it! began to help literally immediately after 6 hours it became noticeable! overall, I think it's pretty good!

A very good antibiotic. He copes with sinusitis at 5 +. At first, there is something incomprehensible, like side effects. Well, then everything goes away. I like the result.

OH, I also had such nausea from him, I could hardly walk, my head was sinking, and bitterness, along with some kind of sweetness in my throat, stood all 5 days (appointed by a gastroenterologist), I almost died from taking it, I hope that my helika felt same way:-)

At a temperature of 38 and coughing, the doctor prescribed 500 mg 2 times a day. After the 3rd dose, impassable bitterness in the mouth, all turned yellow, after which she stopped taking it. This has never happened with other antibiotics. And why is it considered the best?

Well, this medicine is described right here that you really begin to believe in its exceptional value. I'm actually very careful with antibiotics. No wonder they are called antibiotics. They also destroy living organisms. Moreover, they are not selective. They destroy everything. The consequences of taking antibiotics can then come around for more than one month. Therefore, these drugs can only be used in special cases.

Clarithromycin is a macrolide antibiotic with bacteriostatic and, in high concentrations, bactericidal action associated with the suppression of protein synthesis in microorganism cells due to the binding of the drug to the 50S subunit of bacterial ribosomes. Many microorganisms are sensitive to clarithromycin, including intracellular (Chlamydia pneumoniae, Chlamydia trachomatis, (Mycoplasma pneumoniae, Ureaplasma urealyticum, Legionella pneumophila), gram-positive (Staphylococcus spp., Streptococcus spp. (including Streptococcus pneumoniae, Streptococcus pyogenes), Corynebacterium spp. , Listeria monocytogenes) and gram-negative (Haemophilus parainfluenzae, Haemophilus influenzae, Haemophilus ducreyi, Helicobacter pylori, Moraxella catarrhalis, Pasteurella multocida, Neisseria meningitidis, Bordetella pertussis, Campylobacter spp., Borrelia burgdorferi) representatives of human bacterial microflora, a number of anaerobes (Mycoplasma pneumoniae, spp., Eubacterium spp., Clostridium perfringens, Propionibacterium spp., Toxoplasma gondii, Bacteroides melaninogenicus), as well as mycobacteria (Mycobacterium avium complex, including Mycobacterium intracellulare and Mycobacterium avium).

Clarithromycin is rapidly absorbed from the gastrointestinal tract, and if the drug was taken after a heavy snack, then, naturally, its absorption will be reduced.

However, in the end, this does not affect the bioavailability of this antibiotic: its stable concentration in the blood will be established on the 2-3rd day from the start of administration. Elderly patients take clarithromycin without any restrictions, unless, of course, they experience serious kidney problems. But liver problems do not affect the dosing regimen of clarithromycin in any way and do not require dose adjustment.

Clarithromycin is available in tablets. For adults and children over 12 years of age, a single dose is 250-500 mg twice a day. The duration of treatment is 1-2 weeks. The presence of a patient's history of chronic liver disease makes monitoring of serum enzymes mandatory when taking clarithromycin. Cross-resistance between this drug, clindamycin and lincomycin is likely, so some microorganisms resistant to the last two antibiotics may be insensitive to clarithromycin. Long-term and repeated use of the drug can provoke the resistance of both bacterial and fungal microflora, which can lead to a secondary infection. In such cases, the drug should be stopped and switched to a different method of antibiotic therapy.

Pharmacology

Semi-synthetic macrolide antibiotic. Suppresses the synthesis of proteins in the microbial cell, interacting with the 50S ribosomal subunit of bacteria. It acts mainly bacteriostatically, as well as bactericidal.

Active against gram-positive bacteria: Streptococcus spp., Staphylococcus spp., Listeria monocytogenes, Corynebacterium spp.; gram-negative bacteria: Helicobacter pylori, Haemophilus influenzae, Haemophilus ducreyi, Moraxella catarrhalis, Bordetella pertussis, Neisseria gonorrhoeae, Neisseria meningitidis, Borrelia burgdorferi; anaerobic bacteria: Eubacterium spp., Peptococcus spp., Propionibacterium spp., Clostridium perfringens, Bacteroides melaninogenicus; intracellular microorganisms: Legionella pneumophila, Chlamydia trachomatis, Chlamydophila pneumoniae, Ureaplasma urealyticum, Mycoplasma pneumoniae.

It is also active against Toxoplasma gondii, Mycobacterium spp. (except for Mycobacterium tuberculosis).

Pharmacokinetics

When administered orally, clarithromycin is well absorbed from the gastrointestinal tract. Eating slows down absorption, but does not affect the bioavailability of the active substance.

Clarithromycin penetrates well into biological fluids and tissues of the body, where it reaches a concentration 10 times higher than in plasma.

Approximately 20% of clarithromycin is immediately metabolized to form the main metabolite 14-hydroclarithromycin.

At a dose of 250 mg T 1/2 is 3-4 hours, at a dose of 500 mg - 5-7 hours.

It is excreted in the urine unchanged and as metabolites.

Release form

Tablets, film-coated, white, oval, biconvex.

Excipients: pregelatinized starch 100.8 mg, microcrystalline cellulose 68 mg, croscarmellose sodium 38 mg, povidone (K-30) 38 mg, colloidal silicon dioxide 7.6 mg, magnesium stearate 7.6 mg.

The composition of the film shell: Opadry II white 22 mg, including polyvinyl alcohol, titanium dioxide, macrogol, talc.

7 pcs. - blister packs (aluminum/PVC) (1) - cardboard packs.
7 pcs. - blister packs (aluminum/PVC) (2) - cardboard packs.
10 pieces. - blister packs (aluminum/PVC) (1) - cardboard packs.
10 pieces. - blister packs (aluminum/PVC) (2) - cardboard packs.
12 pcs. - blister packs (aluminum/PVC) (1) - cardboard packs.
12 pcs. - blister packs (aluminum/PVC) (2) - cardboard packs.

Dosage

Individual. When taken orally for adults and children over 12 years of age, a single dose is 0.25-1 g, the frequency of administration is 2 times / day.

For children under 12 years of age, the daily dose is 7.5-15 mg / kg / day in 2 divided doses.

In children, clarithromycin should be used in the appropriate dosage form intended for this category of patients.

The duration of treatment depends on the indications.

Maximum daily doses: for adults - 2 g, for children - 1 g.

Interaction

Clarithromycin inhibits the activity of the CYP3A4 isoenzyme, which leads to a slowdown in the rate of metabolism of astemizole with their simultaneous use. As a result, there is an increase in the QT interval and an increased risk of developing ventricular arrhythmia of the "pirouette" type.

Simultaneous administration of clarithromycin with lovastatin or simvastatin is contraindicated due to the fact that these statins are largely metabolized by the CYP3A4 isoenzyme, and the combined use of clarithromycin with clarithromycin increases their serum concentrations, which leads to an increased risk of myopathy, including rhabdomyolysis. Cases of rhabdomyolysis have been reported in patients taking clarithromycin concomitantly with these drugs. If clarithromycin is required, lovastatin or simvastatin should be discontinued for the duration of therapy.

Clarithromycin should be used with caution in combination therapy with other statins. It is recommended to use statins that do not depend on the metabolism of the CYP3A isoenzyme (for example, fluvastatin). If co-administration is necessary, it is recommended to take the lowest dose of the statin. The development of signs and symptoms of myopathy should be monitored. With simultaneous use with atorvastatin, the concentration of atorvastatin in the blood plasma moderately increases, and the risk of developing myopathy increases.

Drugs that are inducers of CYP3A (eg, rifampicin, phenytoin, carbamazepine, phenobarbital, St. It is necessary to control the plasma concentration of the CYP3A inducer, which may increase due to inhibition of CYP3A by clarithromycin.

When combined with rifabutin, the concentration of rifabutin in the blood plasma increases, the risk of developing uveitis increases, and the concentration of clarithromycin in the blood plasma decreases.

When combined with clarithromycin, an increase in plasma concentrations of phenytoin, carbamazepine, valproic acid is possible.

Strong inducers of isoenzymes of the cytochrome P450 system, such as efavirenz, nevirapine, rifampicin, rifabutin and rifapentine, can accelerate the metabolism of clarithromycin and, thus, lower the plasma concentration of clarithromycin and weaken its therapeutic effect, and at the same time increase the concentration of 14-OH-clarithromycin - metabolite, which is also microbiologically active. Since the microbiological activity of clarithromycin and 14-OH-clarithromycin differs in relation to different bacteria, the therapeutic effect may be reduced when clarithromycin and enzyme inducers are used together.

Plasma concentration of clarithromycin decreases with the use of etravirine, while the concentration of the active metabolite 14-OH-clarithromycin increases. Since 14-OH-clarithromycin has low activity against MAC infections, the overall activity against their pathogens may change, so alternative treatment should be considered for the treatment of MAC.

A pharmacokinetic study showed that co-administration of ritonavir 200 mg every 8 hours and clarithromycin 500 mg every 12 hours resulted in a marked suppression of clarithromycin metabolism. When co-administered with ritonavir, C max of clarithromycin increased by 31%, C min increased by 182% and AUC increased by 77%, while the concentration of its metabolite 14-OH-clarithromycin was significantly reduced. Ritonavir should not be co-administered with clarithromycin at doses greater than 1 g/day.

Clarithromycin, atazanavir, saquinavir are substrates and inhibitors of CYP3A, which determines their bidirectional interaction. When saquinavir is co-administered with ritonavir, the potential effect of ritonavir on clarithromycin should be considered.

With simultaneous use with zidovudine, the bioavailability of zidovudine is slightly reduced.

Colchicine is a substrate for both CYP3A and P-glycoprotein. Clarithromycin and other macrolides are known to be inhibitors of CYP3A and P-glycoprotein. When clarithromycin and colchicine are co-administered, inhibition of P-glycoprotein and/or CYP3A may lead to an increased effect 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, more often in elderly patients. Some of the reported cases have occurred in patients with renal insufficiency. Some cases have been reported to have resulted in death. The simultaneous use of clarithromycin and colchicine is contraindicated.

With the combined use of midazolam and clarithromycin (500 mg orally 2 times / day), an increase in the AUC of midazolam was noted: 2.7 times after intravenous administration of midazolam and 7 times after oral administration. Co-administration of clarithromycin with oral midazolam is contraindicated. If intravenous midazolam is used with clarithromycin, the patient should be carefully monitored for possible dose adjustments. The same precautions should be applied to other benzodiazepines that are metabolized by CYP3A, including triazolam and alprazolam. For benzodiazepines whose excretion is independent of CYP3A (temazepam, nitrazepam, lorazepam), a clinically significant interaction with clarithromycin is unlikely.

With the combined use of clarithromycin and triazolam, effects on the central nervous system, such as drowsiness and confusion, are possible. With this combination, it is recommended to monitor the symptoms of CNS disorders.

With simultaneous use with warfarin, it is possible to increase the anticoagulant effect of warfarin and increase the risk of bleeding.

It is assumed that digoxin is a substrate for P-glycoprotein. Clarithromycin is known to inhibit P-glycoprotein. With simultaneous use with digoxin, a significant increase in the concentration of digoxin in the blood plasma and the risk of developing glycoside intoxication are possible.

Perhaps the occurrence of ventricular tachycardia type "pirouette" with the combined use of clarithromycin and quinidine or disopyramide. While taking clarithromycin with these drugs, regular ECG monitoring should be carried out for an increase in the QT interval, and serum concentrations of these drugs should also be monitored. In post-marketing use, cases of hypoglycemia have been reported with the co-administration of clarithromycin and disopyramide. It is necessary to control the concentration of glucose in the blood while the use of clarithromycin and disopyramide. It is believed that it is possible to increase the concentration of disopyramide in the blood plasma due to inhibition of its metabolism in the liver under the influence of clarithromycin.

Co-administration of fluconazole at a dose of 200 mg daily and clarithromycin at a dose of 500 mg 2 times / day caused an increase in the average value of the minimum equilibrium concentration of clarithromycin (C min) and AUC by 33% and 18%, respectively. At the same time, co-administration did not significantly affect the average equilibrium concentration of the active metabolite 14-OH-clarithromycin. Dose adjustment of clarithromycin is not required in case of concomitant use of fluconazole.

Clarithromycin and itraconazole are substrates and inhibitors of CYP3A, which determines their bidirectional interaction. Clarithromycin may increase plasma concentrations of itraconazole, while itraconazole may increase plasma concentrations of clarithromycin.

With simultaneous use with methylprednisolone, the clearance of methylprednisolone decreases; with prednisone - cases of development of acute mania and psychosis are described.

With simultaneous use with omeprazole, the concentration of omeprazole increases significantly and the concentration of clarithromycin in the blood plasma slightly increases; with lansoprazole - glossitis, stomatitis and / or the appearance of a dark color of the tongue are possible.

With simultaneous use with sertraline, the development of serotonin syndrome cannot theoretically be excluded; with theophylline - it is possible to increase the concentration of theophylline in the blood plasma.

With simultaneous use with terfenadine, it is possible to slow down the rate of metabolism of terfenadine and increase its concentration in blood plasma, which can lead to an increase in the QT interval and an increased risk of developing ventricular arrhythmia of the "pirouette" type.

Inhibition of the activity of the isoenzyme CYP3A4 under the influence of clarithromycin leads to a slowdown in the rate of metabolism of cisapride with their simultaneous use. As a result, the concentration of cisapride in the blood plasma increases and the risk of developing life-threatening cardiac arrhythmias, including ventricular arrhythmias of the "pirouette" type, increases.

The primary metabolism of tolterodine is carried out with the participation of CYP2D6. However, in the part of the population lacking CYP2D6, metabolism occurs with the participation of CYP3A. In this population, suppression of CYP3A results in significantly higher serum concentrations of tolterodine. Therefore, in patients with low levels of CYP2D6-mediated metabolism, a dose reduction of tolterodine may be required in the presence of CYP3A inhibitors such as clarithromycin.

With the combined use of clarithromycin and oral hypoglycemic agents (for example, sulfonylurea derivatives) and / or insulin, severe hypoglycemia may occur. Concomitant use of clarithromycin with certain hypoglycemic drugs (eg, nateglinide, pioglitazone, repaglinide, and rosiglitazone) may lead to inhibition of the CYP3A isoenzyme by clarithromycin, which may lead to the development of hypoglycemia. It is believed that with simultaneous use with tolbutamide, there is a possibility of developing hypoglycemia.

With simultaneous use with fluoxetine, a case of the development of toxic effects caused by the action of fluoxetine is described.

While taking clarithromycin with other ototoxic drugs, especially aminoglycosides, care must be taken and control of the functions of the vestibular and hearing aids both during therapy and after its completion.

With simultaneous use with cyclosporine, the concentration of cyclosporine in the blood plasma increases, there is a risk of increased side effects.

With simultaneous use with ergotamine, dihydroergotamine, cases of increased side effects of ergotamine and dihydroergotamine are described. Post-marketing studies show that when clarithromycin is used together with ergotamine or dihydroergotamine, the following effects associated with acute poisoning with drugs of the ergotamine group are possible: vascular spasm, ischemia of the extremities and other tissues, including the central nervous system. The concomitant use of clarithromycin and ergot alkaloids is contraindicated.

Each of these PDE inhibitors is metabolized, at least in part, with the participation of CYP3A. At the same clarithromycin is able to inhibit CYP3A. Co-administration of clarithromycin with sildenafil, tadalafil, or vardenafil may result in an increased inhibitory effect on PDE. With these combinations, dose reduction of sildenafil, tadalafil and vardenafil should be considered.

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

Side effects

From the digestive system: often - diarrhea, vomiting, dyspepsia, nausea, pain in the abdomen; infrequently - esophagitis, gastroesophageal reflux disease, gastritis, proctalgia, stomatitis, glossitis, bloating, constipation, dry mouth, belching, flatulence, increased blood bilirubin concentration, increased activity of ALT, ACT, GGT, alkaline phosphatase, LDH, cholestasis, hepatitis , incl. cholestatic and hepatocellular; frequency unknown - acute pancreatitis, discoloration of the tongue and teeth, liver failure, cholestatic jaundice.

Allergic reactions: often - rash; infrequently - anaphylactoid reaction, hypersensitivity, bullous dermatitis, itching, urticaria, maculo-papular rash; frequency unknown - anaphylactic reaction, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome).

From the nervous system: often - headache, insomnia; infrequently - loss of consciousness, dyskinesia, dizziness, drowsiness, tremor, anxiety, irritability; frequency unknown - convulsions, psychotic disorders, confusion, depersonalization, depression, disorientation, hallucinations, nightmares, paresthesia, mania.

From the side of the skin: often - intense sweating; frequency unknown - acne, hemorrhages.

From the senses: often - dysgeusia, taste perversion; infrequently - vertigo, hearing loss, ringing in the ears; frequency unknown - deafness, ageusia, parosmia, anosmia.

From the side of the cardiovascular system: often - vasodilation; infrequently - cardiac arrest, atrial fibrillation, prolongation of the QT interval on the ECG, extrasystole, atrial flutter; frequency unknown - ventricular tachycardia, incl. pirouette type.

From the urinary system: infrequently - an increase in the concentration of creatinine, a change in the color of urine; frequency unknown - renal failure, interstitial nephritis.

On the part of metabolism and nutrition: infrequently - anorexia, decreased appetite, increased urea concentration, changes in the albumin-globulin ratio

From the musculoskeletal system: infrequently - muscle spasm, musculoskeletal stiffness, myalgia; frequency unknown - rhabdomyolysis, myopathy.

From the respiratory system: infrequently - asthma, epistaxis, pulmonary embolism.

From the hemopoietic system: infrequently - leukopenia, neutropenia, eosinophilia, thrombocythemia; frequency unknown - agranulocytosis, thrombocytopenia.

From the blood coagulation system: infrequently - an increase in the value of MHO, prolongation of prothrombin time.

Local reactions: very often - phlebitis at the injection site, often - pain at the injection site, inflammation at the injection site.

On the part of the body as a whole: infrequently - malaise, hyperthermia, asthenia, chest pain, chills, fatigue.

Indications

Treatment of infectious and inflammatory diseases caused by pathogens sensitive to clarithromycin: infections of the upper respiratory tract and upper respiratory tract (tonsillopharyngitis, otitis media, acute sinusitis); infections of the lower respiratory tract (acute bronchitis, exacerbation of chronic bronchitis, community-acquired bacterial and atypical pneumonia); odontogenic infections; skin and soft tissue infections; mycobacterial infections (M.avium complex, M.kansasii, M.marinum, M.leprae) and their prevention in AIDS patients; eradication of Helicobacter pylori in patients with duodenal ulcer or gastric ulcer (only as part of combination therapy).

Contraindications

A history of QT prolongation, ventricular arrhythmia, or torsades de pointes; hypokalemia (risk of prolongation of the QT interval); severe liver failure occurring simultaneously with renal failure; cholestatic jaundice/hepatitis in history, developed during the use of clarithromycin; porphyria; I trimester of pregnancy; lactation period (breastfeeding); simultaneous administration of clarithromycin with astemizole, cisapride, pimozide, terfenadine; with ergot alkaloids, eg ergotamine, dihydroergotamine; with midazolam for oral administration; with HMG-CoA reductase inhibitors (statins), which are largely metabolized by the CYP3A4 isoenzyme (lovastatin, simvastatin), with colchicine; with ticagrelor or ranolazine; hypersensitivity to clarithromycin and other macrolides.

Application features

Use during pregnancy and lactation

Use in the first trimester of pregnancy is contraindicated.

Application in the II and III trimesters of pregnancy is possible only in cases where the intended benefit to the mother outweighs the potential risk to the fetus.

If necessary, use during lactation should stop breastfeeding.

Application for violations of liver function

Application for violations of kidney function

Use in children

special instructions

Clarithromycin should be used with caution in patients with moderate to severe renal impairment; liver failure of moderate and severe degree, with coronary artery disease, severe heart failure, hypomagnesemia, severe bradycardia (less than 50 bpm); simultaneously with benzodiazepines, such as alprazolam, triazolam, midazolam for intravenous administration; simultaneously with other ototoxic drugs, especially aminoglycosides; simultaneously with drugs that are metabolized by the CYP3A isoenzyme (including carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants, quinidine, rifabutin, sildenafil, tacrolimus, vinblastine; simultaneously with CYP3A4 inducers (including rifampicin , phenytoin, carbamazepine, phenobarbital, St. John's wort); simultaneously with statins, the metabolism of which does not depend on the CYP3A isoenzyme (including fluvastatin); simultaneously with blockers of slow calcium channels, which are metabolized by the CYP3A4 isoenzyme (including verapamil, amlodipine, diltiazem); simultaneously with class I A antiarrhythmic drugs (quinidine, procainamide) and class III (dofetilide, amiodarone, sotalol).

There is cross-resistance between macrolide antibiotics.

Antibiotic treatment alters the normal intestinal flora, so superinfection caused by resistant microorganisms is possible.

It should be borne in mind that severe persistent diarrhea may be due to the development of pseudomembranous colitis.

Prothrombin time should be monitored periodically in patients receiving clarithromycin concomitantly with warfarin or other oral anticoagulants.

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The site provides reference information for informational purposes only. Diagnosis and treatment of diseases should be carried out under the supervision of a specialist. All drugs have contraindications. Expert advice is required!

Instructions for use clarithromycin

How to take clarithromycin tablets or capsules correctly?

High doses of the drug are required to treat severe infections such as chronic sinusitis, pneumonia, infection caused by mycobacteria. In such cases, prescribe 1 gram of antibiotic 2 times a day. The standard dose for most infections in adults is 500 mg twice daily. In patients with chronic renal failure, a dose of not more than 250 mg twice a day is used.

Should the drug be taken before or after meals?

Given this feature, it is recommended to make an interval between taking an antibiotic and eating about 1 hour. Do not take it during or immediately after a meal. It is best to eat well, wait about an hour and only then take a pill. Taking the pill on an empty stomach is also not recommended, because fasting reduces blood sugar, which can cause fainting.

Does the drug have a bitter taste?

How long should I continue treatment with clarithromycin?

If a person has kidney or liver disease, you can not continue the course for more than 14 days. In other cases, the patient should not interrupt the course of treatment on his own, for example, with the first improvement in his condition or in the absence of positive changes in the first two days of using the drug. Such a short use of the antibiotic leads to the fact that a small part of the microorganisms remains in the body, which also acquires resistance to clarithromycin. As a result, the disease returns with more dangerous symptoms and requires stronger antibiotics to treat it.

Clarithromycin treatment regimen for eradication ( removal) Helicobacter

The most common eradication regimen ( removal) Helicobacter consists of the following drugs:

• proton pump inhibitor ( omeprazole 20 mg twice a day). It is used to reduce the formation of hydrochloric acid, which damages the weakened gastric mucosa.
• Clarithromycin ( 500 mg 2 times a day). The main antibacterial agent against Helicobacter pylori.
• Amoxicillin ( 1000 mg 2 times a day) or metronidazole ( 500 mg 2 times a day). An additional antibiotic with a different mechanism of action.

How to use the drug intravenously?

Intravenous administration of clarithromycin usually involves the use of 1 gram of antibiotic per day, divided into 2 equal doses. The contents of the vial ( powder) dissolves in physiological saline ( volume from 250 ml to 500 ml) and is injected through a dropper for 60 minutes or more into the superficial veins of the forearm. More rapid administration is prohibited, since the drug is poorly soluble in water and saline. Preparation of the solution, finding and puncture of the vein is carried out by medical personnel. Intravenous administration is used in patients with severe bacterial infections. After 2-5 days of treatment, they are transferred to the tablet form of the drug.

Can the drug be administered intramuscularly?

How quickly does the drug start to work?

About one-fifth of the drug almost immediately goes through a series of chemical transformations in the liver, but still remains active against microorganisms. Part of the drug accumulates in the gallbladder, slowly enters the intestines and is reabsorbed from there. Due to this, a second peak in the concentration of clarithromycin in the blood occurs after a few hours. A feature of this antibiotic is a good distribution in soft tissues ( the drug penetrates well into the skin, lungs, muscles, middle ear, genitals), where its concentration can be 10 times higher than the content in the blood.

It is important to note that a single dose of clarithromycin does not provide sufficient antibacterial activity. In order to achieve the death of pathogenic flora, it is necessary to constantly maintain a certain concentration of the antibiotic in the blood. That is why it is very important to take clarithromycin tablets regularly and continue treatment until the end of the course.

How long does it take for the drug to leave the body?

In people with kidney damage, the half-life of the drug increases. That is why for this category of patients, a dose adjustment of the antibiotic is required. As a rule, for kidney disease, no more than 250 mg of clarithromycin is prescribed at a single dose. This reduces the toxicity of the drug and reduces the risk of side effects.

Shelf life and storage conditions of the drug

The drug should be stored at normal room temperature ( 15 to 25 degrees). You shouldn't keep it in the refrigerator. It is recommended to store it in its original packaging in order to have information about the production date and expiration date. The drug must be protected from direct sunlight and from accidental use by children, as this may pose a threat to their health.

Contraindications to the use of clarithromycin

• hypersensitivity ( allergy) to the components of the drug;
• porphyria;
• lactation period ( breastfeeding);
• children's age up to 6 months;
• concomitant use of certain drugs pimozide, terfenadine, astemizole).

Porphyria is a hereditary disease that is characterized by a violation of the production of hemoglobin in the liver. Taking this antibiotic seriously changes the functioning of the liver, which can provoke the transition of porphyria into an acute form. In addition, clarithromycin alters the functioning of the liver so much that most drugs are excreted differently from the body, which can change their effect. Taking other medications is not a contraindication to the use of clarithromycin, but extreme caution should be exercised when combining different medications.

Hypersensitivity to clarithromycin

The patient is usually unaware that he is allergic to any antibiotic. In order to exclude the development of allergic reactions, you can conduct special tests with an allergist, which will reliably indicate the presence of an allergy. This test can be performed simultaneously for several antibiotics. Such tests are almost mandatory for those who suffer from other allergic diseases, drug or food allergies. With any prescription of drugs, it is recommended to inform the doctor about all cases of allergic manifestations throughout life.

Can I use the drug for diseases of the liver and kidneys?

It is believed that with a slight violation of liver function, dose adjustment is not required, as this is compensated by an increase in the excretion of clarithromycin by the kidneys. However, with functional kidney damage ( creatinine excretion rate less than 30 ml/min) dose adjustment may be required. This can be explained by the fact that the kidneys play a large role in the excretion of clarithromycin. It should also be taken into account that severe renal or hepatic insufficiency are strict contraindications to the use of clarithromycin.

Can clarithromycin be used during pregnancy and breastfeeding?

If you want to use the drug during breastfeeding, then doctors advise temporarily switching to artificial feeding. The antibiotic passes into breast milk and can harm the young body of the child. The drug can cause allergies in a child, lead to toxic damage to the liver or kidneys, and other harmful phenomena.

Despite all the risks, if the potential benefit from the use of clarithromycin is sufficiently high, this drug can still be used in pregnant women. However, this requires the informed consent of the patient after weighing all the pros and cons. It should be borne in mind that today there are no antibacterial agents that would not have a harmful effect on the fetus.

Can clarithromycin be used in children?

The use of higher doses of clarithromycin in animals, carried out in the course of special studies, has led to serious consequences. So, many of the test subjects had disorders in the functioning of the kidneys, liver, lymphatic system, organs of vision and genital organs. In order to avoid such disorders in children, parents should use as few antibiotics as possible. Any treatment of children with antibiotics must be agreed with the pediatrician.

Side effects of clarithromycin

Clarithromycin may cause the following side effects:

• Nervous system disorders. Characterized by the appearance of headache, dizziness, anxiety. In isolated cases, hallucinations and acute psychoses develop.

• Disorders of the sense organs. In some cases, after using the drugs, changes in taste perception, tinnitus, and impaired skin sensitivity were noted. Very rarely, patients report hearing loss, which disappears after discontinuation of the drug.
• Disorders of the gastrointestinal tract. Nausea, vomiting, diarrhea are relatively common ( diarrhea), increased activity of liver enzymes ( detected after a biochemical blood test). In isolated cases, the use of the drug leads to jaundice, acute liver failure.
• Disorders of the cardiovascular system. They are rare, mainly associated with a change in the rhythm of the heartbeat ( arrhythmias).
• Changes in the hematopoietic system. Antibiotics have the ability to slow down cell division. This drug slightly reduces the rate of formation of platelets ( blood elements responsible for its coagulation). For the patient, this may become noticeable in the form of bleeding of unusual duration, the formation of subcutaneous hemorrhages.
• Allergic reactions. The development of an allergy is an indication for the abolition of clarithromycin. Allergy to the drug can manifest itself in the form of a skin rash, redness of the skin, swelling, difficulty breathing, pain in the upper abdomen and many other symptoms.
• Return of infection with the development of resistance of microorganisms. This side effect occurs, as a rule, when the rules for taking an antibiotic are violated. If the entire course of treatment has not been completed, a part of pathogenic microorganisms remains in the body, moreover, only one that, in the course of mutations, has acquired resistance to the antibiotic. Further multiplication of bacteria leads to the formation of a new population of bacteria, in which the majority have resistance to the previously used antibiotic.

stool disorder ( diarrhoea, diarrhea) when using the drug

In order to get rid of dysbacteriosis and restore the normal intestinal microflora, it is necessary to follow a certain diet. It must include dairy products kefir), enriched with bifidobacteria. Doctors also sometimes prescribe probiotics ( Linex and others), which help to create the best conditions for the reproduction of beneficial intestinal bacteria.

Does the drug have a harmful effect on the liver and kidneys?

Clarithromycin poisoning and overdose

In case of poisoning with clarithromycin, as a first aid, you need to help the patient clear the stomach of the contents and give him sorbents ( Activated carbon). With their help, the absorption of that part of the drug that is still in the intestine will stop. After that, you need to seek help from qualified medical personnel. Unfortunately, the manufacturer indicates that hemodialysis ( blood purification using a special apparatus) is ineffective in clarithromycin poisoning. Therefore, in case of poisoning with this antibiotic, doctors use various symptomatic agents.

Interactions of clarithromycin with other drugs ( omeprazole, amoxicillin, fluconazole)

Modern medicine prohibits combining clarithromycin with cisapride, pimozide, terfenadine. This dangerous combination can lead to arrhythmia and even cardiac arrest. Clarithromycin enhances the effect of indirect anticoagulants, carbamazepine, midazolam, digoxin, rifabutin and other drugs, which is why it is necessary to calculate the dose of drugs very accurately when they are combined.

Clarithromycin increases the blood concentration and duration of omeprazole, a bismuth drug used in gastric ulcer treatment regimens. This effect is not always clinically significant, but somewhat increases the quality of treatment.

Fluconazole is an antifungal drug that is used on the third day of antibiotic therapy to prevent the development of fungal infections. It has been scientifically proven that it favorably affects the duration of the drug in the body.

When clarithromycin is combined with other antibiotics ( such as amoxicillin) it is necessary to take into account the possibility of cross-resistance of microorganisms. Scientists have proven that if the bacterial flora is resistant to other macrolides, as well as lincomycin and clindamycin, then the use of clarithromycin will most likely not give the desired results. Thus, the problem of drug interactions is quite complex. The possibility of combining different drugs should be determined by the doctor.

Can clarithromycin be combined with alcohol?

Prices for clarithromycin in Russian cities

The cost of various formulations of the drug clarithromycin

Do I need a prescription to buy clarithromycin?