Clarithromycin Ecositrin 14 film-coated tablets 500 mg

Compound:

Each tablet contains:

Active substance:

clarithromycin (in terms of active substance) 250.0 mg; 500.0 mg

Description

Capsule-shaped biconvex tablets, pink film-coated. On a cross section, two layers are visible, the inner layer is white or almost white.

Pharmacological group:

antibiotic - macrolide.

ATX code:

J01FA09.

Pharmacological properties:

Pharmacodynamics. Semi-synthetic broad-spectrum macrolide antibiotic. Disturbs the protein synthesis of microorganisms (binds to the 50S subunit of the ribosomes of the microbial cell). Acts on externally and intracellularly located pathogens. The activity of clarithromycin against most of the following microorganisms has been proven in vitro and in clinical practice - aerobic gram-positive microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes; aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Legionella pneumophila; other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae; mycobacteria: Mycobacterium avium complex (MAC) - a complex including: Mycobacterium avium and Micobacterium intracellulare; Helycobacter pylori.

Beta-lactamases do not affect the activity of clarithromycin.

Activity of clarithromycin in vitro - aerobic gram-positive microorganisms: Listeria monocytogenes, Streptococcus agalactiae, Streptococci groups C,F,G, Streptococci group viridans; aerobic gram-negative microorganisms: Neisseria gonorrhoeae, Bordetella pertussis, Pasteurella multocida; anaerobic gram-positive microorganisms: Clostridium perfringens, Peptococcus niger, Propionibacterium acnes; anaerobic gram-negative microorganisms: Bacteroides melaninogenicus; spirochetes: Borrelia burgdorferi, Treponema pallidum; mycobacteria: Mycobacterium leprae, Mucobacterium chelonae, campylobacteria: Campylobacter jejuni.

The microbiologically active metabolite of clarithromycin, 14-hydroxyclarithromycin, is twice as active as the parent compound against Haemophilus influenzae. Clarithromycin and its metabolite in combination may have either additive or synergistic effects on Haemophilus influenzae in vitro and in vivo, depending on the strain of the bacterium.

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

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

Pharmacokinetics

Absorption is fast. Food slows absorption without significantly affecting bioavailability. Bioavailability of 250 mg tablets is 50%. Bonding with plasma proteins is 65-75%. After a single dose, two peaks of maximum concentration (Cmax) are recorded. The second peak is due to the ability of the drug to accumulate in the gallbladder, followed by gradual or rapid entry into the intestine and absorption. The time to reach maximum concentration (TCmax) when taking 250 mg is 2-3 hours.

After oral administration, 20-30% of the dose taken is quickly hydroxylated in the liver by cytochrome CYP3A4, CYP3A5 and CYP3A7 isoenzymes to form the main metabolite - 14-hydroxyclarithromycin, which has pronounced antimicrobial activity against Haemophllus influenzae. It is an inhibitor of the CYP3A4, CYP3A5 and CYP3A7 isoenzymes.

When taken regularly at 250 mg/day, the equilibrium concentration (Css) of the unchanged drug and its main metabolite is 1 and 0.6 μg/ml, respectively; half-life is 3-4 and 5-6 hours, respectively. When the dose is increased to 500 mg/day, Css of the unchanged drug and its metabolite in plasma is 2.7-2.9 and 0.83-0.88 μg/ml, respectively; half-life is 4.8-5 and 6.9-8.7 hours, respectively. At therapeutic concentrations it accumulates in the lungs, skin and soft tissues (their concentrations are 10 times higher than the level of the antibiotic in the blood plasma).

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

If renal function is impaired, there is an increase in TCmax, Cmax and the area under the concentration-time curve (AUC) of clarithromycin and its metabolite.

Description of the drug ECOZITRIN®

Clarithromycin inhibits the activity of the CYP3A4 isoenzyme, which leads to a slower rate of metabolism of astemizole when used simultaneously. As a result, there is an increase in the QT interval and an increased risk of developing ventricular arrhythmias.

Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated due to the fact that these statins are largely metabolized by the CYP3A4 isoenzyme, and co-administration 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 do not depend on the metabolism of CYP3A isoenzymes (for example, fluvastatin). If coadministration is necessary, it is recommended to take the lowest dose of statin. The development of signs and symptoms of myopathy should be monitored. When used simultaneously with atorvastatin, the concentration of atorvastatin in the blood plasma increases moderately and the risk of developing myopathy increases.

Drugs that are CYP3A inducers (for example, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort) can induce the metabolism of clarithromycin, which can lead to subtherapeutic concentrations of clarithromycin and a decrease in its effectiveness. It is necessary to monitor the plasma concentration of the CYP3A inducer, which may increase due to the inhibition of CYP3A by clarithromycin.

When used together 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 used together with clarithromycin, plasma concentrations of phenytoin, carbamazepine, and valproic acid may increase.

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, reduce the concentration of clarithromycin in plasma 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 against different bacteria, the therapeutic effect may be reduced when clarithromycin is used together with enzyme inducers.

The plasma concentration of clarithromycin decreases with the use of etravirine, while the concentration of the active metabolite 14-OH-clarithromycin increases. Because 14-OH-clarithromycin has low activity against MAC infections, overall activity against MAC infections may be affected, and alternative treatments 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 the metabolism of clarithromycin. When co-administered with ritonavir, clarithromycin Cmax increased by 31%, Cmin 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 in doses exceeding 1 g/day.

Clarithromycin, atazanavir, and saquinavir are substrates and inhibitors of CYP3A, which determines their bidirectional interaction. When taking saquinavir with ritonavir, consider the potential effect of ritonavir on clarithromycin.

When used simultaneously with zidovudine, the bioavailability of zidovudine is slightly reduced.

Colchicine is a substrate of both CYP3A and P-glycoprotein. Clarithromycin and other macrolides are known to be inhibitors of CYP3A and P-glycoprotein. When clarithromycin and colchicine are taken together, inhibition of P-glycoprotein 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 with renal failure. Some cases were reported to be fatal. The simultaneous use of clarithromycin and colchicine is contraindicated.

When midazolam and clarithromycin were used together (orally 500 mg 2 times a day), an increase in the AUC of midazolam was noted:

• 2.7 times after intravenous administration of 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 CYP3A (temazepam, nitrazepam, lorazepam), a clinically significant interaction with clarithromycin is unlikely.

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

When used simultaneously with warfarin, the anticoagulant effect of warfarin may be enhanced and the risk of bleeding may increase.

Digoxin is thought to be a substrate for P-glycoprotein. Clarithromycin is known to inhibit P-glycoprotein. When used simultaneously with digoxin, there may be a significant increase in the concentration of digoxin in the blood plasma and the risk of developing glycoside intoxication.

Ventricular tachycardia of the “pirouette” type may occur with the combined use of clarithromycin and quinidine or disopyramide. When clarithromycin is coadministered with these drugs, ECG monitoring should be performed regularly to monitor for QT interval prolongation, 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. 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 a day caused an increase in the mean minimum equilibrium concentration of clarithromycin (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.

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.

When used simultaneously with methylprednisolone, the clearance of methylprednisolone decreases; with prednisone - cases of acute mania and psychosis have been described.

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

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

When used simultaneously with terfenadine, it is possible to slow down the rate of metabolism of terfenadine and increase its concentration in the blood plasma, which can lead to an increase in the QT interval and an increased risk of developing ventricular arrhythmias.

Inhibition of the activity of the CYP3A4 isoenzyme under the influence of clarithromycin leads to a slower rate of metabolism of cisapride when used simultaneously. As a result, the concentration of cisapride in the blood plasma increases and the risk of developing life-threatening cardiac arrhythmias, including ventricular arrhythmias, 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, inhibition of CYP3A results in significantly higher serum concentrations of tolterodine. Therefore, in patients with low levels of CYP2D6-mediated metabolism, a reduction in the dose of tolterodine may be required in the presence of CYP3A inhibitors such as clarithromycin.

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 result in inhibition of CYP3A isoenzymes by clarithromycin, which may lead to hypoglycemia. It is believed that when used concomitantly with tolbutamide, there is a risk of developing hypoglycemia.

When used simultaneously with fluoxetine, a case of the development of toxic effects caused by the action of fluoxetine has been described.

When taking clarithromycin concomitantly with other ototoxic drugs, especially aminoglycosides, caution should be exercised and the functions of the vestibular and auditory systems should be monitored both during and after therapy.

When used simultaneously with cyclosporine, the concentration of cyclosporine in the blood plasma increases, and there is a risk of increased side effects.

When used simultaneously with ergotamine and dihydroergotamine, cases of increased side effects of ergotamine and dihydroergotamine have been described. Post-marketing studies show that when clarithromycin is used concomitantly with ergotamine or dihydroergotamine, 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. Concomitant use of clarithromycin and ergot alkaloids is contraindicated.

Each of these PDE inhibitors is metabolized, at least in part, by CYP3A. However, clarithromycin can inhibit CYP3A. Concomitant use of clarithromycin with sildenafil, tadalafil or vardenafil may lead to an increase in the inhibitory effect on PDE. With these combinations, consider reducing the dose of sildenafil, tadalafil and vardenafil.

When using clarithromycin simultaneously with calcium channel blockers 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 calcium channel blockers, may increase with simultaneous use. Arterial hypotension, bradyarrhythmia and lactic acidosis are possible when taking clarithromycin and verapamil simultaneously.

Indications for use:

Adults: pharyngitis, tonsillitis, acute sinusitis, exacerbation of chronic bronchitis, community-acquired pneumonia, uncomplicated infections of the skin and subcutaneous tissue; disseminated infection caused by Mycobacteiium avium and Mycobacterium intracellulare.

Adults in combination with amoxicillin and omeprazole/lansoprazole as triple therapy for infections caused by Helicobacter pylori, including duodenal ulcer.

Children: pharyngitis, tonsillitis, community-acquired pneumonia, acute sinusitis, acute otitis media, uncomplicated infections of the skin and subcutaneous tissue; disseminated infection caused by Mycobacterium avium and Mycobacterium intracellulare.

Contraindications:

Hypersensitivity, porphyria, lactation period, simultaneous use of cisapride, astemizole, pimozide, terfenadine, ergotamine and other ergot alkaloids, oral dosage forms of midazolam, alprazolam, triazolam.

Children up to 12 years of age (for this dosage form).

Lactose intolerance or lactase deficiency, as well as glucose-galactose malabsorption.

Concomitant use with lovastatin and simvastatin, with oral midazolam, with colchicine in patients with impaired renal or hepatic function taking inhibitors

P-glycoprotein or potent inhibitors of the CYP3A4 isoenzyme; patients have a history of QT interval prolongation, ventricular arrhythmia, or torsade de pointes; cholestatic jaundice/hepatitis that occurred during the use of clarithromycin (history); severe liver failure occurring simultaneously with renal failure, hypokalemia.

Clarithromycin Ecositrin film-coated tablets 500 mg 14 pcs. in Moscow

When clarithromycin is taken together and drugs that are primarily metabolized by the CYP3A isoenzyme, a mutual increase in their concentrations is possible, which can enhance or prolong both therapeutic and side effects. Concomitant use with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, as well as with lovastatin and simvastatin is contraindicated.

Drugs that are CYP3A inducers (for example, phenobarbital and St. John's wort) may induce the metabolism of clarithromycin. This may result in subtherapeutic levels of clarithromycin, resulting in reduced effectiveness.

Prescribed with caution with carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants (including warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine, as well as phenytoin, theophylline and valproic acid (metabolized through other cytochrome P450 isoenzymes). Use with caution with alprazolam, triazolam, midazolam for intravenous administration. It is necessary to adjust the dose of the drug and control the concentration in the blood.

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

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

Efavirenz, nevirapine, rifampicin, rifabutin and rifapentine (cytochrome P450 inducers) reduce the plasma level of clarithromycin and weaken the therapeutic effect of the latter, while at the same time increasing the level of 14-hydroxyclarithromycin.

When co-administered with fluconazole at a dose of 200 mg daily and clarithromycin at a dose of 1 g/day, the Css and AUC of clarithromycin may increase by 33% and 18%, respectively. No dose adjustment of clarithromycin is required.

When co-administered with ritonavir 600 mg/day and clarithromycin 1 g/day, it is possible to reduce the metabolism of clarithromycin (increase in Cmax by 31%, Css by 182% and AUC by 77%), and completely suppress the formation of 14-hydroxyclarithromycin. In patients with chronic renal failure, dose adjustment is necessary: ​​with creatinine clearance (CC) 30-

60 ml/min, the dose of clarithromycin should be reduced by 50%, with CC less

30 ml/min at 75%. Ritonavir should not be taken together with clarithromycin at a dose exceeding 1 g/day.

When taken together with quinidine and disopyramide, ventricular tachycardia of the “pirouette” type may occur. Monitoring of ECG (increased QT interval) and serum concentrations of these drugs is necessary.

Clarithromycin increases the concentrations of HMG-CoA reductase inhibitors (lovastatin, simvastatin). Rhabdomyolysis may develop in patients taking these drugs together.

When using clarithromycin and omeprazole, the Cmax, AUC and half-life of omeprazole may increase by 30%, 89% and 34%, respectively. The average gastric pH over 24 hours was 5.2 when taking omeprazole alone and 5.7 when taking omeprazole with clarithromycin.

When using clarithromycin and indirect anticoagulants, the effect of the latter may be enhanced. When used simultaneously with warfarin and other indirect anticoagulants, it is necessary to monitor the international normalized ratio and prothrombin time.

When using clarithromycin with sildenafil, tadalafil or vardenafil (phosphodiesterase-5 inhibitors), an increase in the inhibitory effect on phosphodiesterase is possible. A dose reduction of sildenafil, tadalafil and vardenafil may be required.

When clarithromycin is used together with theophylline and carbamazepine, the concentration of the latter in the systemic circulation may increase.

When using clarithromycin with tolterodine in patients who are poor metabolizers via CYP2D6, a reduction in the dose of tolterodine may be necessary in the presence of clarithromycin (a CYP3A inhibitor).

When clarithromycin (1 g/day) is taken together with midazolam (orally), the AUC of midazolam may increase by 7 times. Dosage adjustments may be required when midazolam (intravenous) and clarithromycin are used. The same precautions should be applied to other benzodiazepines that are metabolized by CYP3A. For benzodiazepines whose elimination is independent of CYP3A (temazepam, nitrazepam, lorazepam), a clinically significant interaction with clarithromycin is unlikely.

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

When clarithromycin and digoxin are co-administered, the concentration of digoxin in the serum should be carefully monitored (its concentration may increase and the development of potentially fatal arrhythmias may occur).

Concomitant use of clarithromycin and zidovudine in adult HIV-infected patients may result in a decrease in the Css of zidovudine. It is necessary to select doses of clarithromycin and zidovudine. This type of interaction does not occur in HIV-infected children receiving clarithromycin suspension with zidovudine.

When taking clarithromycin (l g/day) and atazanavir (400 mg/day) together, it is possible to increase the AUC of atazanavir by 28%, clarithromycin by 2 times, and reduce the AUC of 14-hydroxyclarithromycin by 70%. In patients with CC 30-60 ml/min, the dose of clarithromycin should be reduced by 50%. Clarithromycin in doses exceeding 1 g/day should not be co-administered with protease inhibitors.

When clarithromycin and intraconazole are taken together, a mutual increase in the concentration of drugs in plasma is possible. Patients taking itraconazole and clarithromycin concomitantly should be closely monitored due to the possible enhancement or prolongation of the pharmacological effects of these drugs.

With simultaneous administration of clarithromycin (l g / day) and saquinavir (in soft gelatin capsules, 1200 mg 3 times a day), the AUC and Css of saquinavir may increase by 177% and 187%, respectively, and clarithromycin by 40%. When these two drugs are co-administered for a limited time at the doses/formulations indicated above, no dose adjustment is required.

When taken together with verapamil, a decrease in blood pressure, bradyarrhythmia and lactic acidosis are possible.

With the simultaneous use of clarithromycin and oral hypoglycemic agents, including insulin, hypoglycemia may develop in rare cases. Careful monitoring of blood glucose concentrations is recommended.

When taken concomitantly with clarithromycin (500 mg 2 times a day), etravirine reduces the plasma concentration of clarithromycin by 53% and increases the concentration of the active metabolite, 14-hydroxyclarithromycin, by 46%. Because 14-hydroxyclarithromycin has reduced activity against Mycobacterium avium complex (MAC), the overall activity of clarithromycin and its metabolite against this pathogen may be altered.

Carefully:

Renal and/or liver failure, myasthenia gravis, concomitant use of drugs metabolized by the liver, concomitant use of colchicine.

Concomitant use with drugs that induce and are metabolized by the CYP3A4 isoenzyme, benzodiazepines (alprazolam, triazolam, midazolam for intravenous use), class IA and III antiarrhythmic drugs, blockers of “slow” calcium channels that are metabolized by the CYP3A4 isoenzyme; in patients with ischemic heart disease, severe heart failure, hypomagnesemia, severe bradycardia, myasthenia gravis.

Use during pregnancy and lactation:

The safety of clarithromycin during pregnancy has not been established. During pregnancy, especially in the first trimester, it is recommended to prescribe clarithromycin if the benefits of its use outweigh the potential risks to the fetus and/or there is no safer alternative therapy. If pregnancy occurs while taking the drug, the patient should be warned about the possible risks to the fetus. If it is necessary to prescribe the drug during lactation, the issue of stopping breastfeeding should be resolved.

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Directions for use and dosage:

Take orally, swallow the tablets without chewing, with a small amount of liquid.

Adults and children over 12 years of age and weighing more than 33 kg:

• for pharyngitis and tonsillitis caused by Streptococcus pyogenes - 250 mg every 12 hours for 10 days;
• for acute sinusitis, 500 mg every 12 hours for 14 days;
• for exacerbation of chronic bronchitis caused by Haemophilus influenzae - 500 mg every 12 hours for 7-14 days, caused by Haemophilus parainfluenzae - 500 mg every 12 hours for 7 days; caused by Moraxella catarrhalis, Streptococcus pneumoniae - 250 mg every 12 hours for 7-14 days;
• for community-acquired pneumonia caused by Haemophilus influenzae - 250 mg every 12 hours for 7 days, caused by Streptococcus pneumoniae, Chlamydia pneumoniae, Mycoplasma pneumoniae - 250 mg every 12 hours for 7-14 days;
• for uncomplicated infections of the skin and subcutaneous tissue caused by Staphylococcus aureus, Streptococcus pyogenes - 250 mg every 12 hours for 7-14 days.

In the treatment and prevention of infections caused by Mycobacterium avium

prescribed 500 mg 2 times a day. The maximum daily dose is 1000 mg. Duration of treatment – ​​6 months. and more.

To eradicate Helicobacter pylori:

Combined treatment with three drugs:

clarithromycin - 500 mg, lansoprazole - 30 mg and amoxicillin - 1000 mg 2 times a day for 10-14 days;

clarithromycin - 500 mg, omeprazole - 20 mg and amoxicillin - 1000 mg 2 times a day for 10 days.

Combined treatment with two drugs:

Clarithromycin - 500 mg 3 times a day, omeprazole - 40 mg per day for 14 days, with the prescription of omeprazole for the next 14 days at a dose of 20 mg per day.

For patients with chronic renal failure:

(creatinine clearance less than 30 ml/min or serum creatinine concentration more than 3.3 mg/100 ml), the dose is reduced by 2 times, or the interval is increased by 2 times. The maximum duration of treatment for patients in this group is 14 days.

Ecositrine

When taking clarithromycin together and drugs that are primarily metabolized by CYP3A isoenzymes, a mutual increase in their concentrations is possible, which can enhance or prolong both therapeutic and side effects. Concomitant use with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, alprazolam, midazolam, triazolam is contraindicated.

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

When used together with cisapride, pimozide, terfenadine and astemizole, it is possible to increase the concentration of the latter in the blood, prolong the QT interval, and cause arrhythmia, including ventricular tachycardia. type "pirouette" and ventricular fibrillation.

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

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

When co-administered with fluconazole at a dose of 200 mg daily and clarithromycin at a dose of 1 g/day, the Css and AUC of clarithromycin may increase by 33% and 18%, respectively. No dose adjustment of clarithromycin is required.

When co-administered with ritonavir 600 mg/day and clarithromycin 1 g/day, it is possible to reduce the metabolism of clarithromycin (increase in Cmax by 31%, Css by 182% and AUC by 77%), and completely suppress the formation of 14-hydroxyclarithromycin. In patients with chronic renal failure, dose adjustment is necessary: ​​with a CC of 30-60 ml/min, the dose of clarithromycin should be reduced by 50%, with a CC of less than 30 ml/min by 75%. Ritonavir should not be taken together with clarithromycin at a dose exceeding 1 g/day.

When taken together with quinidine and disopyramide, ventricular tachycardia of the “pirouette” type may occur. Monitoring of ECG (increased QT interval) and serum concentrations of these drugs is necessary.

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

When using clarithromycin and omeprazole, it is possible to increase the Cmax, AUC and T1/2 of omeprazole by 30%, 89% and 34%, respectively. The average pH value in the stomach over 24 hours was 5.2 when taking omeprazole alone and 5.7 when taking omeprazole together with clarithromycin.

When using clarithromycin and indirect anticoagulants, the effect of the latter may be enhanced.

When using clarithromycin with sildenafil, tadalafil or vardenafil (PDE5 inhibitors), an increase in the inhibitory effect on PDE is possible. A dose reduction of PDE5 inhibitors may be required.

When clarithromycin is co-administered with theophylline and carbamazepine, the concentration of the latter in the systemic circulation may increase.

When using clarithromycin with tolterodine in patients with low CYP2D6 activity, a dose reduction of tolterodine may be required in the presence of clarithromycin (an inhibitor of CYP3A isoenzymes).

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

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

When clarithromycin and digoxin are co-administered, the concentration of digoxin in the serum should be carefully monitored (its concentration may increase and the development of potentially fatal arrhythmias may occur).

Concomitant use of clarithromycin (regular-release tablets) and zidovudine in adult HIV-infected patients may result in a decrease in the Css of zidovudine. It is necessary to select doses of clarithromycin and zidovudine. This type of interaction does not occur in HIV-infected children receiving clarithromycin suspension with zidovudine.

When taking clarithromycin (1 g/day) and atazanavir (400 mg/day) together, the AUC of atazanavir may increase by 28%, clarithromycin by 2 times, and the AUC of 14-hydroxyclarithromycin may decrease by 70%. In patients with CC 30-60 ml/min, the dose of clarithromycin should be reduced by 50%. Clarithromycin in doses exceeding 1 g/day should not be co-administered with protease inhibitors.

When clarithromycin and itraconazole are taken together, a mutual increase in the concentration of drugs in plasma is possible. Patients taking itraconazole and clarithromycin simultaneously should be closely monitored due to the possible enhancement or prolongation of the pharmacological effects of these drugs.

With simultaneous administration of clarithromycin (1 g / day) and saquinavir (in soft gelatin capsules, 1200 mg 3 times a day), the AUC and Css of saquinavir may increase by 177% and 187%, respectively, and clarithromycin by 40%. When these two drugs are prescribed together for a limited time at the doses/doses indicated above, no dose adjustment is required.

When taken together with verapamil, a decrease in blood pressure, bradyarrhythmia, and lactic acidosis is possible.

Side effect:

From the nervous system:

headache, dizziness, drowsiness, anxiety, insomnia, nightmares, tremors, convulsions, depression; disorientation, hallucinations, psychosis, depersonalization, confusion, increased symptoms of myasthenia gravis, psychotic disorders, paresthesia, mania, intense sweating, anorexia, malaise, asthenia, chills, fatigue.

From the digestive system:

nausea, belching, vomiting, flatulence, loss of appetite gastritis, gastralgia, diarrhea, stomatitis, glossitis, candidiasis of the oral mucosa, discoloration of the tongue and teeth, dryness of the oral mucosa, acute pancreatitis, increased activity of “liver” transaminases, cholestasis, hepatocellular and cholestatic hepatitis, cholestatic jaundice, rarely - pseudomembranous colitis, liver failure with a fatal outcome, mainly due to severe concomitant diseases and/or concomitant drug therapy, dyspepsia, constipation.

From the cardiovascular system:

ventricular tachycardia, incl. pirouette type, ventricular flutter and fibrillation, increased QT interval on the ECG.

From the senses:

noise, ringing in the ears, vertigo, changes in taste (dysgeusia), ageusia, in isolated cases - hearing loss that goes away after discontinuation of the drug, impaired sense of smell, anosmia.

From the skin and soft tissues:

erythrasma, acne, erysipelas.

From the musculoskeletal system:

myalgia, myopathy, chest pain.

From the hematopoietic organs:

rarely - thrombocytopenia (unusual bleeding, hemorrhage), agranulocytosis, thrombocytosis, prolongation of prothrombin time, increased INR levels.

From the urinary system:

interstitial nephritis, renal failure.

Laboratory indicators:

leukopenia, neutropenia, eosinophilia, increased concentration of bilirubin in the blood, hypercreatininemia, hypoglycemia (including while taking hypoglycemic drugs), change in urine color.

Allergic reactions

- skin rash, itching, urticaria, skin hyperemia, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis, anaphylactic reactions, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), Henoch-Schönlein purpura, hemorrhages.

Other:

secondary infections (development of resistance of microorganisms).

Ecozitrin®

When clarithromycin is taken together and drugs that are primarily metabolized by the CYP3A isoenzyme, a mutual increase in their concentrations is possible, which can enhance or prolong both therapeutic and side effects.

Concomitant use with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, as well as with lovastatin and simvastatin is contraindicated.

Drugs that are CYP3A inducers (for example, phenobarbital and St. John's wort) may induce the metabolism of clarithromycin. This may result in subtherapeutic levels of clarithromycin, resulting in reduced effectiveness. Prescribed with caution with carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants (including warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine, as well as phenytoin, theophylline and valproic acid (metabolized through other isoenzymes of cytochrome P450).

Use with caution with alprazolam, triazolam, midazolam for intravenous administration. It is necessary to adjust the dose of the drug and control the concentration in the blood.

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

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

Efavirenz, nevirapine, rifampicin, rifabutin and rifapentine (cytochrome P450 inducers) reduce the plasma level of clarithromycin and weaken the therapeutic effect of the latter, while at the same time increasing the level of 14-hydroxyclarithromycin.

When co-administered with fluconazole at a dose of 200 mg daily and clarithromycin at a dose of 1 g/day, the Css and AUC of clarithromycin may increase by 33% and 18%, respectively. No dose adjustment of clarithromycin is required. When co-administered with ritonavir 600 mg/day and clarithromycin 1 g/day, it is possible to reduce the metabolism of clarithromycin (increase in Cmax by 31%, Css by 182% and AUC by 77%), and completely suppress the formation of 14-hydroxyclarithromycin. In patients with chronic renal failure, dose adjustment is necessary: ​​with creatinine clearance (CC) 30-60 ml/min, the dose of clarithromycin should be reduced by 50%, with CL less than 30 ml/min by 75%. Ritonavir should not be taken together with clarithromycin at a dose exceeding 1 g/day.

When taken together with quinidine and disopyramide, ventricular tachycardia of the “pirouette” type may occur. Monitoring of ECG (increased QT interval) and serum concentrations of these drugs is necessary. Clarithromycin increases the concentrations of HMG-CoA reductase inhibitors (lovastatin, simvastatin). Rhabdomyolysis may develop in patients taking these drugs together.

When using clarithromycin and omeprazole, it is possible to increase the Cmax, AUC and half-life of omeprazole by 30%, 89% and 34%, respectively. The average gastric pH over 24 hours was 5.2 when taking omeprazole alone and 5.7 when taking omeprazole with clarithromycin.

When using clarithromycin and indirect anticoagulants, the effect of the latter may be enhanced. When used simultaneously with warfarin and other indirect anticoagulants, it is necessary to monitor the international normalized ratio and prothrombin time.

When using clarithromycin with sildenafil, tadalafil or vardenafil (phosphodiesterase-5 inhibitors), an increase in the inhibitory effect on phosphodiesterase is possible. A dose reduction of sildenafil, tadalafil and vardenafil may be required.

When clarithromycin is used together with theophylline and carbamazepine, the concentration of the latter in the systemic circulation may increase.

When using clarithromycin with tolterodine in patients who are poor metabolizers via CYP2D6, a reduced dose of tolterodine may be required in the presence of clarithromycin (a CYP3A inhibitor).

When clarithromycin (1 g/day) is taken together with midazolam (orally), the AUC of midazolam may increase by 7 times. Dosage adjustments may be required when midazolam (intravenous) and clarithromycin are used. The same precautions should be applied to other benzodiazepines that are metabolized by CYP3A. For benzodiazepines whose elimination is not dependent on CYP3A (temazepam, nitrazepam, lorazepam), a clinically significant interaction with clarithromycin is unlikely.

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

When clarithromycin and digoxin are co-administered, the concentration of digoxin in the serum should be carefully monitored (its concentration may increase and the development of potentially fatal arrhythmias may occur). Concomitant use of clarithromycin and zidovudine in adult HIV-infected patients may result in a decrease in the Css of zidovudine. It is necessary to select doses of clarithromycin and zidovudine. This type of interaction does not occur in HIV-infected children receiving clarithromycin suspension with zidovudine.

When taking clarithromycin (1 g/day) and atazanavir (400 mg/day) together, the AUC of atazanavir may increase by 28%, clarithromycin by 2 times, and the AUC of 14-hydroxyclarithromycin may decrease by 70%. In patients with CC 30-60 ml/min, the dose of clarithromycin should be reduced by 50%. Clarithromycin in doses exceeding 1 g/day should not be administered together with protease inhibitors. When clarithromycin and itraconazole are taken together, a mutual increase in the concentration of drugs in plasma is possible. Patients taking itraconazole and clarithromycin concomitantly should be closely monitored due to the possible enhancement or prolongation of the pharmacological effects of these drugs. With simultaneous administration of clarithromycin (1 g / day) and saquinavir (in soft gelatin capsules, 1200 mg 3 times a day), the AUC and Css of saquinavir may increase by 177% and 187%, respectively, and clarithromycin by 40%. When these two drugs are co-administered for a limited time at the doses/formulations indicated above, no dose adjustment is required. When taken together with verapamil, a decrease in blood pressure, bradyarrhythmia and lactic acidosis are possible.

With the simultaneous use of clarithromycin and oral hypoglycemic agents, including insulin, hypoglycemia may develop in rare cases. Careful monitoring of blood glucose concentrations is recommended.

When taken concomitantly with clarithromycin (500 mg 2 times a day), etravirine reduces the plasma concentration of clarithromycin by 53% and increases the concentration of the active metabolite, 14-hydroxyclarithromycin, by 46%. Because 14-hydroxyclarithromycin has reduced activity against Mycobacterium avium complex (MAC), the overall activity of clarithromycin and its metabolite against this pathogen may be altered.

Interaction with other drugs:

When clarithromycin is taken together and drugs that are primarily metabolized by the CYP3A isoenzyme, a mutual increase in their concentrations is possible, which can enhance or prolong both therapeutic and side effects. Concomitant use with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, as well as with lovastatin and simvastatin is contraindicated.

Drugs that are CYP3A inducers (for example, phenobarbital and St. John's wort) may induce the metabolism of clarithromycin. This may result in subtherapeutic levels of clarithromycin, resulting in reduced effectiveness.

Prescribed with caution with carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants (including warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine, as well as phenytoin, theophylline and valproic acid (metabolized through other cytochrome P450 isoenzymes). Use with caution with alprazolam, triazolam, midazolam for intravenous administration. It is necessary to adjust the dose of the drug and control the concentration in the blood.

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

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

Efavirenz, nevirapine, rifampicin, rifabutin and rifapentine (cytochrome P450 inducers) reduce the plasma level of clarithromycin and weaken the therapeutic effect of the latter, while at the same time increasing the level of 14-hydroxyclarithromycin.

When co-administered with fluconazole at a dose of 200 mg daily and clarithromycin at a dose of 1 g/day, the Css and AUC of clarithromycin may increase by 33% and 18%, respectively. No dose adjustment of clarithromycin is required.

When co-administered with ritonavir 600 mg/day and clarithromycin 1 g/day, it is possible to reduce the metabolism of clarithromycin (increase in Cmax by 31%, Css by 182% and AUC by 77%), and completely suppress the formation of 14-hydroxyclarithromycin. In patients with chronic renal failure, dose adjustment is necessary: ​​with creatinine clearance (CC) 30-

60 ml/min, the dose of clarithromycin should be reduced by 50%, with CC less

30 ml/min at 75%. Ritonavir should not be taken together with clarithromycin at a dose exceeding 1 g/day.

When taken together with quinidine and disopyramide, ventricular tachycardia of the “pirouette” type may occur. Monitoring of ECG (increased QT interval) and serum concentrations of these drugs is necessary.

Clarithromycin increases the concentrations of HMG-CoA reductase inhibitors (lovastatin, simvastatin). Rhabdomyolysis may develop in patients taking these drugs together.

When using clarithromycin and omeprazole, the Cmax, AUC and half-life of omeprazole may increase by 30%, 89% and 34%, respectively. The average gastric pH over 24 hours was 5.2 when taking omeprazole alone and 5.7 when taking omeprazole with clarithromycin.

When using clarithromycin and indirect anticoagulants, the effect of the latter may be enhanced. When used simultaneously with warfarin and other indirect anticoagulants, it is necessary to monitor the international normalized ratio and prothrombin time.

When using clarithromycin with sildenafil, tadalafil or vardenafil (phosphodiesterase-5 inhibitors), an increase in the inhibitory effect on phosphodiesterase is possible. A dose reduction of sildenafil, tadalafil and vardenafil may be required.

When clarithromycin is used together with theophylline and carbamazepine, the concentration of the latter in the systemic circulation may increase.

When using clarithromycin with tolterodine in patients who are poor metabolizers via CYP2D6, a reduction in the dose of tolterodine may be necessary in the presence of clarithromycin (a CYP3A inhibitor).

When taking clarithromycin together

(1 g/day) with midazolam (oral) it is possible to increase the AUC of midazolam by 7 times. Dosage adjustments may be required when midazolam (intravenous) and clarithromycin are used. The same precautions should be applied to other benzodiazepines that are metabolized by CYP3A. For benzodiazepines whose elimination is independent of CYP3A (temazepam, nitrazepam, lorazepam), a clinically significant interaction with clarithromycin is unlikely.

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

When clarithromycin and digoxin are co-administered, the concentration of digoxin in the serum should be carefully monitored (its concentration may increase and the development of potentially fatal arrhythmias may occur).

Concomitant use of clarithromycin and zidovudine in adult HIV-infected patients may result in a decrease in the Css of zidovudine. It is necessary to select doses of clarithromycin and zidovudine. This type of interaction does not occur in HIV-infected children receiving clarithromycin suspension with zidovudine.

When taking clarithromycin (l g/day) and atazanavir (400 mg/day) together, it is possible to increase the AUC of atazanavir by 28%, clarithromycin by 2 times, and reduce the AUC of 14-hydroxyclarithromycin by 70%. In patients with CC 30-60 ml/min, the dose of clarithromycin should be reduced by 50%. Clarithromycin in doses exceeding 1 g/day should not be co-administered with protease inhibitors.

When clarithromycin and intraconazole are taken together, a mutual increase in the concentration of drugs in plasma is possible. Patients taking itraconazole and clarithromycin concomitantly should be closely monitored due to the possible enhancement or prolongation of the pharmacological effects of these drugs.

With simultaneous administration of clarithromycin (l g / day) and saquinavir (in soft gelatin capsules, 1200 mg 3 times a day), the AUC and Css of saquinavir may increase by 177% and 187%, respectively, and clarithromycin by 40%. When these two drugs are co-administered for a limited time at the doses/formulations indicated above, no dose adjustment is required.

When taken together with verapamil, a decrease in blood pressure, bradyarrhythmia and lactic acidosis are possible.

With the simultaneous use of clarithromycin and oral hypoglycemic agents, including insulin, hypoglycemia may develop in rare cases. Careful monitoring of blood glucose concentrations is recommended.

When taken concomitantly with clarithromycin (500 mg 2 times a day), etravirine reduces the plasma concentration of clarithromycin by 53% and increases the concentration of the active metabolite, 14-hydroxyclarithromycin, by 46%. Because 14-hydroxyclarithromycin has reduced activity against Mycobacterium avium complex (MAC), the overall activity of clarithromycin and its metabolite against this pathogen may be altered.

Clarithromycin Ecositrin tablet p/pl/o 250 mg N14 (Avva-Rus)

When clarithromycin is taken together and drugs that are primarily metabolized by the CYP3A isoenzyme, a mutual increase in their concentrations is possible, which can enhance or prolong both therapeutic and side effects. Concomitant use with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids is contraindicated; alprazolam, midazolam, triazolam. Prescribed with caution with carbamazepine, cilostazol, cyclosporine, disopyramide, lovastatin, methylprednisolone, omeprazole, indirect anticoagulants (including warfarin), quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, vinblasti nom, as well as phenytoin , theophylline and valproic acid (metabolized through other isoenzymes of cytochrome P450). When used together with cisapride, pimozide, terfenadine and astemizole, it is possible to increase the concentration of the latter in the blood, increase the QT interval, and cause arrhythmia, including ventricular tachycardia, incl. type "pirouette", and ventricular fibrillation. It is necessary to adjust the dose of the drug and control the concentration in the blood. When used together with ergotamine and dihydroergotamine, acute poisoning with drugs of the ergotamine group is possible (vascular spasm, ischemia of the limbs and other tissues, including the central nervous system). Efavirenz, nevirapine, rifampicin, rifabutin and rifapentine (inducers of cytochrome P450 ) reduce the level of clarithromycin in plasma and weaken the therapeutic effect of the latter, and at the same time increase the level of 14-hydroxyclarithromycin. When taking fluconazole at a dose of 200 mg daily and clarithromycin at a dose of 1 g / day, the CSS and AUC of clarithromycin may increase by 33 and 18 % respectively. No dose adjustment of clarithromycin is required. When ritonavir 600 mg/day and clarithromycin 1 g/day are taken together, a decrease in the metabolism of clarithromycin is possible (increase in Cmax by 31%, CSS by 182% and AUC by 77%), complete suppression of the formation of 14- hydroxyclarithromycin. In patients with chronic renal failure, dose adjustment is necessary: ​​with creatinine Cl 30–60 ml/min, the dose of clarithromycin should be reduced by 50%. When taken together with quinidine and disopyramide, ventricular tachycardia of the “pirouette” type may occur. Monitoring of ECG (increased QT interval) and serum concentrations of these drugs is necessary. Clarithromycin increases the concentrations of HMG-CoA reductase inhibitors (lovastatin, simvastatin). Rhabdomyolysis may develop in patients taking these drugs together. When using clarithromycin and omeprazole, it is possible to increase Cmax, AUC and T1/2 of omeprazole by 30, 89 and 34%, respectively. The average pH value in the stomach over 24 hours was 5.2 when taking omeprazole alone and 5.7 when taking omeprazole together with clarithromycin. When using clarithromycin and indirect anticoagulants, the effect of the latter may be enhanced. When using clarithromycin with sildenafil, tadalafil or vardenafil (phosphodiesterase-5 inhibitors), an increase in the inhibitory effect on phosphodiesterase is possible. A dose reduction of sildenafil, tadalafil and vardenafil may be required. When clarithromycin is used together with theophylline and carbamazepine, the concentration of the latter in the systemic circulation may increase. When using clarithromycin with tolterodine in patients who are poor metabolizers via CYP2D6, a reduction in the dose of tolterodine may be necessary in the presence of clarithromycin (a CYP3A inhibitor). When clarithromycin (1 g/day) is taken together with midazolam (orally), the AUC of midazolam may increase by 7 times. Concomitant oral administration of clarithromycin with midazolam and other benzodiazepines that are metabolized by CYP3A (triazolam and alprazolam) should be avoided. Dosage adjustments may be required when using midazolam (IV) and clarithromycin. The same precautions should be applied to other benzodiazepines that are metabolized by CYP3A. For benzodiazepines whose elimination is independent of CYP3A (temazepam, nitrazepam, lorazepam), a clinically significant interaction with clarithromycin is unlikely. When clarithromycin is taken together with colchicine, the effect of colchicine may be enhanced. It is necessary to monitor the possible development of clinical symptoms of colchicine intoxication, especially in elderly patients and patients with chronic renal failure (fatal cases have been reported). When clarithromycin and digoxin are co-administered, the concentration of digoxin in the serum should be carefully monitored (its concentration may increase and the development of potentially fatal arrhythmias may occur). Concomitant use of clarithromycin and zidovudine in adult HIV-infected patients may result in a decrease in the CSS of zidovudine. It is necessary to select doses of clarithromycin and zidovudine. This type of interaction does not occur in HIV-infected children receiving clarithromycin suspension with zidovudine. When taking clarithromycin (l g/day) and atazanavir (400 mg/day) together, the AUC of atazanavir may increase by 28%, clarithromycin by 2 times and the AUC of 14-hydroxyclarithromycin may decrease by 70%. In patients with creatinine Cl 30–60 ml/min, the dose of clarithromycin should be reduced by 50%. Clarithromycin in doses exceeding 1 g/day should not be co-administered with protease inhibitors. When clarithromycin and intraconazole are taken together, a mutual increase in the concentration of drugs in plasma is possible. Patients taking itraconazole and clarithromycin simultaneously should be closely monitored due to the possible enhancement or prolongation of the pharmacological effects of these drugs. With simultaneous administration of clarithromycin (l g / day) and saquinavir (in soft gelatin capsules, 1200 mg 3 times a day), the AUC and CSS of saquinavir may increase by 177 and 187%, respectively, and clarithromycin by 40%. When these two drugs are co-administered for a limited time in the doses/dosage forms indicated above, no dose adjustment is required. When taken together with verapamil, a decrease in blood pressure, bradyarrhythmia and lactic acidosis are possible. When taken together with quinidine and disopyramide, ventricular tachycardia of the “pirouette” type may occur. Monitoring of ECG (increased QT interval) and serum concentrations of these drugs is necessary. Clarithromycin increases the concentrations of HMG-CoA reductase inhibitors (lovastatin, simvastatin). Rhabdomyolysis may develop in patients taking these drugs together. When using clarithromycin and omeprazole, the Cmax, AUC and T1/2 of omeprazole may increase by 30, 89 and 34%, respectively. The average pH value in the stomach over 24 hours was 5.2 when taking omeprazole alone and 5.7 when taking omeprazole together with clarithromycin. When using clarithromycin and indirect anticoagulants, the effect of the latter may be enhanced. When using clarithromycin with sildenafil, tadalafil or vardenafil (phosphodiesterase-5 inhibitors) may increase the inhibitory effect on phosphodiesterase. A dose reduction of sildenafil, tadalafil and vardenafil may be required. When clarithromycin is used together with theophylline and carbamazepine, the concentration of the latter in the systemic circulation may increase. When using clarithromycin with tolterodine in patients with a low level of metabolism through CYP2D6, a reduction in the dose of tolterodine in the presence of clarithromycin (CYP3A inhibitor) may be required ). When clarithromycin (1 g/day) is taken together with midazolam (orally), the AUC of midazolam may increase by 7 times. Concomitant oral administration of clarithromycin with midazolam and other benzodiazepines that are metabolized by CYP3A (triazolam and alprazolam) should be avoided. Dosage adjustments may be required when using midazolam (IV) and clarithromycin. The same precautions should be applied to other benzodiazepines that are metabolized by CYP3A. For benzodiazepines, the elimination of which does not depend on CYP3A (temazepam, nitrazepam, lorazepam), a clinically significant interaction with clarithromycin is unlikely. When clarithromycin is taken together with colchicine, the effect of colchicine may be enhanced. Monitoring of the possible development of clinical symptoms of colchicine intoxication is necessary, especially in elderly patients and patients with chronic renal failure (fatal cases have been reported). When taking clarithromycin and digoxin together, the concentration of digoxin in the serum should be carefully monitored (an increase in its concentration and the development of potentially fatal arrhythmias). Concomitant use of clarithromycin and zidovudine in adult HIV-infected patients may result in a decrease in the CSS of zidovudine. It is necessary to select doses of clarithromycin and zidovudine. This type of interaction does not occur in HIV-infected children receiving clarithromycin in the form of a suspension together with zidovudine. When taking clarithromycin (l g/day) and atazanavir (400 mg/day) together, the AUC of atazanavir may increase by 28%, clarithromycin by 2 times and a 70% reduction in the AUC of 14-hydroxyclarithromycin. In patients with creatinine Cl 30–60 ml/min, the dose of clarithromycin should be reduced by 50%. Clarithromycin in doses exceeding 1 g/day should not be prescribed together with protease inhibitors. When clarithromycin and intraconazole are taken together, a mutual increase in the concentration of drugs in plasma is possible. Patients taking itraconazole and clarithromycin simultaneously require careful monitoring due to the possible enhancement or prolongation of the pharmacological effects of these drugs. When taking clarithromycin (l g / day) and saquinavir (in soft gelatin capsules, 1200 mg 3 times a day), it is possible the AUC and CSS of saquinavir increased by 177 and 187%, respectively, and clarithromycin by 40%. When these two drugs are prescribed together for a limited time in the doses/dosage forms indicated above, no dose adjustment is required. When taken together with verapamil, a decrease in blood pressure, bradyarrhythmia and lactic acidosis are possible.

Special instructions:

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

Prescribe with caution against drugs metabolized by the liver (it is recommended to measure their concentration in the blood).

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

If a secondary infection develops, adequate therapy should be prescribed.

If severe diarrhea occurs during or after treatment, the diagnosis of pseudomembranous colitis should be excluded, which requires immediate discontinuation of the drug and the appointment of appropriate treatment.

Oral tablets Ecozitrin

Instructions for medical use of the drug

Description of pharmacological action

Semi-synthetic broad-spectrum macrolide antibiotic. Disturbs the protein synthesis of microorganisms (binds to the 50S subunit of the ribosomal membrane of the microbial cell). Acts on extra- and intracellularly located pathogens. The activity of clarithromycin against most of the following microorganisms has been proven in vitro and in clinical practice: aerobic gram-positive microorganisms - Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes; aerobic gram-negative microorganisms - Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Legionella pneumophila; other microorganisms - Mycoplasma pneumoniae, Chlamydia pneumoniae; mycobacteria - Mycobacterium avium complex (MAC) - a complex including: Mycobacterium avium and Mycobacterium intracellulare; Helicobacter pylori. Beta-lactamases do not affect the activity of clarithromycin. Activity of clarithromycin in vitro: aerobic gram-positive microorganisms - Listeria monocytogenes, Streptococcus agalactiae, Streptococci groups C,F,G, Streptococci group viridans; aerobic gram-negative microorganisms - Neisseria gonorrhoeae, Bordetella pertussis, Pasteurella multocida; anaerobic gram-positive microorganisms - Clostridium perfringens, Peptococcus niger, Propionibacterium acnes; anaerobic gram-negative microorganisms - Bacteroides melaninogenicus; spirochetes - Borrelia burgdorferi, Treponema pallidum; mycobacteria - Mycobacterium leprae, Mucobacterium chelonae, campylobacter - Campylobacter jejuni. The microbiologically active metabolite of clarithromycin, 14-hydroxyclarithromycin, is twice as active as the parent compound against Haemophilus influenzae. Clarithromycin and its metabolite in combination may have either additive or synergistic effects on Haemophilus influenzae in vitro and in vivo, depending on the strain of the bacterium. Most strains of staphylococci resistant to methicillin and oxacillin are resistant to clarithromycin. It is possible to develop cross-resistance to clarithromycin and other macrolide antibiotics, as well as lincomycin and clindamycin. Lactulose, which is part of Ecositrin® as a bifidogenic factor, is a synthetic disaccharide, the molecule of which consists of galactose and fructose residues. Lactulose is not absorbed or hydrolyzed in the stomach and upper intestines. Lactulose released from Ecositrin® tablets as a substrate is fermented by the normal microflora of the large intestine, stimulating the growth of bifidobacteria and lactobacilli. As a result of the hydrolysis of lactulose in the large intestine, organic acids are formed - lactic, acetic and formic, which suppress the growth of pathogenic microorganisms and consequently reduce the production of nitrogen-containing toxic substances. Thus, lactulose in Ecositrin® has a protective effect on the normal intestinal microflora, reduces intoxication and eliminates the risk of side effects associated with dysbiosis.

Indications for use

In adults and children: - pharyngitis; - tonsillitis; - acute sinusitis; — community-acquired pneumonia; - uncomplicated infections of the skin and subcutaneous tissue; - disseminated infection caused by Mycobacterium avium and Mycobacterium intracellulare. In adults additionally: - diseases caused by Helicobacter pylori, including duodenal ulcer (as part of combination therapy); - exacerbation of chronic bronchitis. In children additionally: - acute otitis media.

Release form

film-coated tablets 250 mg; contour packaging 4, cardboard pack 1; film-coated tablets 250 mg; contour packaging 4, cardboard pack 2; film-coated tablets 250 mg; polymer jar (jar) 4, cardboard pack 1; film-coated tablets 250 mg; polymer jar (jar) 5, cardboard pack 1; film-coated tablets 250 mg; polymer jar (jar) 7, cardboard pack 1; film-coated tablets 250 mg; polymer jar (jar) 10, cardboard pack 1; film-coated tablets 250 mg; polymer jar (jar) 14, cardboard pack 1; film-coated tablets 250 mg; polymer bottle (bottle) 4, cardboard pack 1; film-coated tablets 250 mg; polymer bottle (bottle) 5, cardboard pack 1; film-coated tablets 250 mg; polymer bottle (bottle) 7, cardboard pack 1; film-coated tablets 250 mg; polymer bottle (bottle) 10, cardboard pack 1; film-coated tablets 250 mg; polymer bottle (bottle) 14, cardboard pack 1; film-coated tablets 250 mg; contour packaging 5, cardboard pack 1; film-coated tablets 250 mg; contour packaging 5, cardboard pack 2; film-coated tablets 250 mg; contour packaging 7, cardboard pack 1; film-coated tablets 250 mg; contour packaging 7, cardboard pack 2; film-coated tablets 250 mg; contour packaging 10, cardboard pack 1; film-coated tablets 250 mg; contour packaging 10, cardboard pack 2; film-coated tablets 250 mg; contour packaging 14, cardboard pack 1; film-coated tablets 500 mg; contour packaging 4, cardboard pack 1; film-coated tablets 500 mg; contour packaging 4, cardboard pack 2; film-coated tablets 500 mg; polymer jar (jar) 4, cardboard pack 1; film-coated tablets 500 mg; polymer jar (jar) 5, cardboard pack 1; film-coated tablets 500 mg; polymer jar (jar) 7, cardboard pack 1; film-coated tablets 500 mg; polymer jar (jar) 10, cardboard pack 1; film-coated tablets 500 mg; polymer jar (jar) 14, cardboard pack 1; film-coated tablets 500 mg; polymer bottle (bottle) 4, cardboard pack 1; film-coated tablets 500 mg; polymer bottle (bottle) 5, cardboard pack 1; film-coated tablets 500 mg; polymer bottle (bottle) 7, cardboard pack 1; film-coated tablets 500 mg; polymer bottle (bottle) 10, cardboard pack 1; film-coated tablets 500 mg; polymer bottle (bottle) 14, cardboard pack 1; film-coated tablets 500 mg; contour packaging 5, cardboard pack 1; film-coated tablets 500 mg; contour packaging 5, cardboard pack 2; film-coated tablets 500 mg; contour packaging 7, cardboard pack 1; film-coated tablets 500 mg; contour packaging 7, cardboard pack 2; film-coated tablets 500 mg; contour packaging 10, cardboard pack 1; film-coated tablets 500 mg; contour packaging 10, cardboard pack 2; film-coated tablets 500 mg; contour packaging 14, cardboard pack 1; Composition Film-coated tablets 1 tablet. Clarithromycin (in terms of active substance) 250 mg, 500 mg. excipients: lactulose (300 or 600 mg, respectively); povidone-K25; magnesium stearate; colloidal silicon dioxide (Aerosil); talc; polacrilin potassium shell composition: hypromellose; talc; titanium dioxide; macrogol-4000; Azorubine dye in contour cell packages of 4, 5, 7, 10 pcs.; in a cardboard pack of 1 or 2 packages or in polymer jars or plastic bottles of 4, 5, 7, 10, 14 pcs.; in a cardboard pack 1 jar or bottle.

Pharmacodynamics

Semi-synthetic broad-spectrum macrolide antibiotic. Disturbs the protein synthesis of microorganisms (binds to the 50S subunit of the ribosomal membrane of the microbial cell). Acts on extra- and intracellularly located pathogens. The activity of clarithromycin against most of the following microorganisms has been proven in vitro and in clinical practice: aerobic gram-positive microorganisms - Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes; aerobic gram-negative microorganisms - Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Legionella pneumophila; other microorganisms - Mycoplasma pneumoniae, Chlamydia pneumoniae; mycobacteria - Mycobacterium avium complex (MAC) - a complex including: Mycobacterium avium and Mycobacterium intracellulare; Helicobacter pylori. Beta-lactamases do not affect the activity of clarithromycin. Activity of clarithromycin in vitro: aerobic gram-positive microorganisms - Listeria monocytogenes, Streptococcus agalactiae, Streptococci groups C,F,G, Streptococci group viridans; aerobic gram-negative microorganisms - Neisseria gonorrhoeae, Bordetella pertussis, Pasteurella multocida; anaerobic gram-positive microorganisms - Clostridium perfringens, Peptococcus niger, Propionibacterium acnes; anaerobic gram-negative microorganisms - Bacteroides melaninogenicus; spirochetes - Borrelia burgdorferi, Treponema pallidum; mycobacteria - Mycobacterium leprae, Mucobacterium chelonae, campylobacter - Campylobacter jejuni. The microbiologically active metabolite of clarithromycin, 14-hydroxyclarithromycin, is twice as active as the parent compound against Haemophilus influenzae. Clarithromycin and its metabolite in combination may have either additive or synergistic effects on Haemophilus influenzae in vitro and in vivo, depending on the strain of the bacterium. Most strains of staphylococci resistant to methicillin and oxacillin are resistant to clarithromycin. It is possible to develop cross-resistance to clarithromycin and other macrolide antibiotics, as well as lincomycin and clindamycin. Lactulose, which is part of Ecositrin® as a bifidogenic factor, is a synthetic disaccharide, the molecule of which consists of galactose and fructose residues. Lactulose is not absorbed or hydrolyzed in the stomach and upper intestines. Lactulose released from Ecositrin® tablets as a substrate is fermented by the normal microflora of the large intestine, stimulating the growth of bifidobacteria and lactobacilli. As a result of the hydrolysis of lactulose in the large intestine, organic acids are formed - lactic, acetic and formic, which suppress the growth of pathogenic microorganisms and consequently reduce the production of nitrogen-containing toxic substances. Thus, lactulose in Ecositrin® has a protective effect on the normal intestinal microflora, reduces intoxication and eliminates the risk of side effects associated with dysbiosis.

Pharmacokinetics

Absorption is high. Food slows absorption without significantly affecting bioavailability. Bioavailability of 250 mg tablets is 50%. Plasma protein binding is 65%–75%. After a single dose, two Cmax peaks are recorded. The second peak is due to the ability of the drug to accumulate in the gallbladder, followed by gradual or rapid entry into the intestine and absorption. Tmax when taken orally at a dose of 250 mg - 2-3 hours. After oral administration, 20-30% of the dose taken is quickly hydroxylated in the liver by cytochrome isoenzymes CYP3A4, CYP3A5 and CYP3A7 with the formation of the main metabolite - 14-hydroxyclarithromycin, which has pronounced antimicrobial activity against Haemophillus influenzae. It is an inhibitor of the CYP3A4, CYP3A5 and CYP3A7 isoenzymes. With regular intake of 250 mg/day, the CSS of the unchanged drug and its main metabolite is 1 and 0.6 μg/ml, respectively; T1/2 - 3–4 and 5–6 hours, respectively. When the dose is increased to 500 mg/day, the CSS of the unchanged drug and its metabolite in plasma is 2.7–2.9 and 0.83–0.88 mcg/ml, respectively; T1/2 - 4.8–5 and 6.9–8.7 hours, respectively. At therapeutic concentrations it accumulates in the lungs, skin and soft tissues (their concentrations are 10 times higher than the level of the antibiotic in the blood plasma). It is excreted by the kidneys and intestines (20%–30% in unchanged form; the rest in the form of metabolites). With a single dose of 250 mg and 1200 mg, 37.9% and 46% are excreted by the kidneys and 40.2% and 29.1% by the intestines, respectively. If renal function is impaired, an increase in Tmax, Cmax and AUC of clarithromycin and its metabolite is observed. Lactulose, which is part of Ecositrin®, does not affect the main pharmacokinetic parameters characterizing the bioavailability of clarithromycin.

Use during pregnancy

The safety of clarithromycin during pregnancy has not been established. During pregnancy, especially in the first trimester, it is recommended to prescribe clarithromycin if the benefits of taking it outweigh the potential risk to the fetus and/or there is no safer therapy with alternative drugs. If pregnancy occurs while taking the drug, the patient should be warned about the possible risk to the fetus. If it is necessary to prescribe the drug during lactation, the issue of stopping breastfeeding should be resolved.

Contraindications for use

- hypersensitivity; - porphyria; - lactation period; - simultaneous use of cisapride, astemizole, pimozide, terfenadine, ergotamine and other ergot alkaloids, oral dosage forms of midazolam, alprazolam, triazolam; - lactose intolerance or lactase deficiency, as well as glucose-galactose malabsorption; - children under 12 years of age (for this dosage form). With caution: renal and/or liver failure, myasthenia gravis, simultaneous use of drugs metabolized in the liver, simultaneous use of colchicine.

Side effects

From the nervous system: headache, dizziness, anxiety, insomnia, nightmares, convulsions, depression, disorientation, hallucinations, psychosis, depersonalization, confusion. From the digestive system: nausea, vomiting, gastralgia, diarrhea, stomatitis, glossitis, candidiasis of the oral mucosa, discoloration of the tongue and teeth, acute pancreatitis, increased activity of liver transaminases, hepatocellular and cholestatic hepatitis, cholestatic jaundice, rarely - pseudomembranous colitis, liver failure with a fatal outcome, mainly due to severe concomitant diseases and/or concomitant drug therapy. Lactulose, which is part of the Ecositrin® drug, eliminates the risk of side effects associated with the negative effect of the antibiotic on the intestinal microbiocenosis. From the cardiovascular system: ventricular tachycardia, incl. pirouette type, ventricular flutter and fibrillation, increased QT interval on the ECG. From the senses: noise, ringing in the ears, changes in taste (dysgeusia), in isolated cases - hearing loss that goes away after discontinuation of the drug, impaired sense of smell. From the musculoskeletal system: myalgia. From the hematopoietic organs: rarely - thrombocytopenia (unusual bleeding, hemorrhage). From the urinary system: interstitial nephritis. Laboratory indicators: leukopenia, hypercreatininemia, hypoglycemia (including while taking hypoglycemic drugs). Allergic reactions: skin rash, itching, urticaria, skin hyperemia, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis, anaphylactic reactions. Other: secondary infections (development of resistance of microorganisms).

Directions for use and doses

Inside, swallow whole, without chewing, with a small amount of liquid. Adults and children over 12 years old, weighing more than 33 kg: - for pharyngitis and tonsillitis caused by Streptococcus pyogenes - 250 mg every 12 hours for 10 days; - for acute sinusitis - 500 mg every 12 hours for 14 days; - for exacerbation of chronic bronchitis caused by Haemophilus influenzae - 500 mg every 12 hours for 7-14 days; caused by Haemophilus parainfluenzae - 500 mg every 12 hours for 7 days; caused by Moraxella catarrhalis, Streptococcus pneumoniae - 250 mg every 12 hours for 7-14 days; - for community-acquired pneumonia caused by Haemophilus influenzae - 250 mg every 12 hours for 7 days; caused by Streptococcus pneumoniae, Chlamydia pneumoniae, Mycoplasma pneumoniae - 250 mg every 12 hours for 7-14 days; - for uncomplicated infections of the skin and subcutaneous tissue caused by Staphylococcus aureus, Streptococcus pyogenes - 250 mg every 12 hours for 7-14 days; - for the treatment and prevention of infections caused by Mycobacterium avium - 500 mg 2 times a day. The maximum daily dose is 1000 mg. Duration of treatment is 6 months or more. For the purpose of eradication of Helicobacter pylori: Combined treatment with three drugs: clarithromycin - 500 mg 2 times a day, lansoprazole - 30 mg 2 times a day and amoxicillin - 1000 mg 2 times a day for 10-14 days; Clarithromycin - 500 mg 2 times a day, omeprazole - 20 mg 2 times a day and amoxicillin - 1000 mg 2 times a day for 10 days. Combined treatment with two drugs: clarithromycin - 500 mg 3 times a day, omeprazole - 40 mg/day for 14 days, with the prescription of omeprazole for the next 14 days at a dose of 20 mg/day. For patients with chronic renal failure: (Cl creatinine less than 30 ml/min or serum creatinine concentration more than 3.3 mg/100 ml) the dose is reduced by 2 times, or the interval between doses is increased by 2 times. The maximum duration of treatment for patients in this group is 14 days.

Overdose

Symptoms: abdominal pain, nausea, vomiting, diarrhea. Treatment: gastric lavage, maintenance therapy. It is not removed by peritoneal or hemodialysis.

Interactions with other drugs

When clarithromycin is taken together and drugs that are primarily metabolized by the CYP3A isoenzyme, a mutual increase in their concentrations is possible, which can enhance or prolong both therapeutic and side effects. Concomitant use with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids is contraindicated; alprazolam, midazolam, triazolam. Prescribed with caution with carbamazepine, cilostazol, cyclosporine, disopyramide, lovastatin, methylprednisolone, omeprazole, indirect anticoagulants (including warfarin), quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, vinblastine, as well as phenytoin, theophylline and valproic acid ( metabolized through other cytochrome P450 isoenzymes). When used together with cisapride, pimozide, terfenadine and astemizole, it is possible to increase the concentration of the latter in the blood, increase the QT interval, and cause arrhythmia, including ventricular tachycardia, incl. type "pirouette", and ventricular fibrillation. It is necessary to adjust the dose of the drug and control the concentration in the blood. When used together with ergotamine and dihydroergotamine, acute poisoning with drugs of the ergotamine group is possible (vascular spasm, ischemia of the limbs and other tissues, including the central nervous system). Efavirenz, nevirapine, rifampicin, rifabutin and rifapentine (cytochrome P450 inducers) reduce the plasma level of clarithromycin and weaken the therapeutic effect of the latter, and at the same time increase the level of 14-hydroxyclarithromycin. When co-administered with fluconazole at a dose of 200 mg daily and clarithromycin at a dose of 1 g/day, the CSS and AUC of clarithromycin may increase by 33 and 18%, respectively. No dose adjustment of clarithromycin is required. When co-administered with ritonavir 600 mg/day and clarithromycin 1 g/day, it is possible to reduce the metabolism of clarithromycin (increase in Cmax by 31%, CSS by 182% and AUC by 77%), and completely suppress the formation of 14-hydroxyclarithromycin. In patients with chronic renal failure, dose adjustment is necessary: ​​with creatinine Cl 30–60 ml/min, the dose of clarithromycin should be reduced by 50%. When taken together with quinidine and disopyramide, ventricular tachycardia of the “pirouette” type may occur. Monitoring of ECG (increased QT interval) and serum concentrations of these drugs is necessary. Clarithromycin increases the concentrations of HMG-CoA reductase inhibitors (lovastatin, simvastatin). Rhabdomyolysis may develop in patients taking these drugs together. When using clarithromycin and omeprazole, it is possible to increase the Cmax, AUC and T1/2 of omeprazole by 30, 89 and 34%, respectively. The average pH value in the stomach over 24 hours was 5.2 when taking omeprazole alone and 5.7 when taking omeprazole together with clarithromycin. When using clarithromycin and indirect anticoagulants, the effect of the latter may be enhanced. When using clarithromycin with sildenafil, tadalafil or vardenafil (phosphodiesterase-5 inhibitors), an increase in the inhibitory effect on phosphodiesterase is possible. A dose reduction of sildenafil, tadalafil and vardenafil may be required. When clarithromycin is used together with theophylline and carbamazepine, the concentration of the latter in the systemic circulation may increase. When using clarithromycin with tolterodine in patients who are poor metabolizers via CYP2D6, a reduction in the dose of tolterodine may be necessary in the presence of clarithromycin (a CYP3A inhibitor). When clarithromycin (1 g/day) is taken together with midazolam (orally), the AUC of midazolam may increase by 7 times. Concomitant oral administration of clarithromycin with midazolam and other benzodiazepines that are metabolized by CYP3A (triazolam and alprazolam) should be avoided. Dosage adjustments may be required when using midazolam (IV) and clarithromycin. The same precautions should be applied to other benzodiazepines that are metabolized by CYP3A. For benzodiazepines whose elimination is independent of CYP3A (temazepam, nitrazepam, lorazepam), a clinically significant interaction with clarithromycin is unlikely. When clarithromycin is taken together with colchicine, the effect of colchicine may be enhanced. It is necessary to monitor the possible development of clinical symptoms of colchicine intoxication, especially in elderly patients and patients with chronic renal failure (fatal cases have been reported). When clarithromycin and digoxin are co-administered, the concentration of digoxin in the serum should be carefully monitored (its concentration may increase and the development of potentially fatal arrhythmias may occur). Concomitant use of clarithromycin and zidovudine in adult HIV-infected patients may result in a decrease in the CSS of zidovudine. It is necessary to select doses of clarithromycin and zidovudine. This type of interaction does not occur in HIV-infected children receiving clarithromycin suspension with zidovudine. When taking clarithromycin (l g/day) and atazanavir (400 mg/day) together, the AUC of atazanavir may increase by 28%, clarithromycin by 2 times and the AUC of 14-hydroxyclarithromycin may decrease by 70%. In patients with creatinine Cl 30–60 ml/min, the dose of clarithromycin should be reduced by 50%. Clarithromycin in doses exceeding 1 g/day should not be co-administered with protease inhibitors. When clarithromycin and intraconazole are taken together, a mutual increase in the concentration of drugs in plasma is possible. Patients taking itraconazole and clarithromycin simultaneously should be closely monitored due to the possible enhancement or prolongation of the pharmacological effects of these drugs. With simultaneous administration of clarithromycin (l g / day) and saquinavir (in soft gelatin capsules, 1200 mg 3 times a day), the AUC and CSS of saquinavir may increase by 177 and 187%, respectively, and clarithromycin by 40%. When these two drugs are co-administered for a limited time in the doses/dosage forms indicated above, no dose adjustment is required. When taken together with verapamil, a decrease in blood pressure, bradyarrhythmia and lactic acidosis are possible.

Special instructions for use

In the presence of chronic liver diseases, it is necessary to regularly monitor the activity of enzymes in the blood serum. Prescribe with caution against the background of drugs metabolized in the liver (it is recommended to measure their concentration in the blood). In case of co-administration with warfarin or other anticoagulants, PT must be monitored. If a secondary infection develops, adequate therapy should be prescribed. If severe diarrhea occurs during or after treatment, the diagnosis of pseudomembranous colitis should be excluded, which requires immediate discontinuation of the drug and the appointment of appropriate treatment.

Storage conditions

List B: In a dry place, protected from light, at a temperature not exceeding 25 °C.

Best before date

36 months

ATX classification:

J Antimicrobials for systemic use

J01 Antimicrobials for systemic use

J01F Macrolides and lincosamides

J01FA Macrolides

J01FA09 Clarithromycin

Release form:

Film-coated tablets 250 mg and 500 mg.

4, 5, 7, 10 tablets in a blister pack made of polyvinyl chloride film or multilayer polyvinyl chloride film and printed varnished aluminum foil.

4, 5, 7, 10, 14 tablets in a plastic bottle with a screw cap or a polymer jar with a screw cap. Self-adhesive labels are placed on the bottle or jar.

1.2 blister packs or 1 bottle or 1 jar together with instructions for use are placed in a cardboard pack.