Clarithromycin - instructions for use, dose, side effects, contraindications

Excipients: cellulose microcrystalline 94.05 mg or 188.11 mg, croscarmellose sodium 11.25 mg or 22.50 mg, povidone 11.25 mg or 22.50 mg, silicon dioxide colloid 2.82 mg or 5.64 mg, magnesium stearate 5.63 mg or 11.25 mg;

film sheath: Fill yellow 7.50 mg or 15.00 mg (contains hypromellose-15cP 4.43 mg or 8.76 mg, propylene glycol 1.26 mg or 2.52 mg, titanium dioxide 1.18 mg or 2.36 mg, giprolose 0.40 mg or 0.78 mg, vanillin 0.16 mg or 0.31 mg, sorbic acid 0.12 mg or 0.25 mg, iron oxide oxide yellow 0.02 mg or 0.037 mg).

Description:

Dosage of 250 mg: oblong form, biconvex tablets covered with a film shell of light yellow color, engraved "D" on one side and engraved "62" on the other. On the cross-section, two layers are visible: the core is almost white, surrounded by a yellow shell.

Dosage 500 mg: oblong form, biconvex tablets, coated with a film coating of light yellow color, engraved "D" on one side and engraved "63" on the other.On the cross-section, two layers are visible: the core is almost white, surrounded by a yellow shell.

Pharmacotherapeutic group:antibiotic-macrolide

ATX: & nbsp

J.01.F.A.09 Clarithromycin

Pharmacodynamics:

Clarithromycin is a semisynthetic derivative of erythromycin A. In a cell of susceptible bacteria clarithromycin exhibits antimicrobial activity by binding the 50S ribosomal subunit and thereby suppressing protein synthesis. It acts on extracorporeal and intracellular pathogens. The nature of the antimicrobial effect of clarithromycin is predominantly bacteriostatic. Beta-lactamases do not affect the activity of clarithromycin.

Clarithromycin shows antibacterial activity in vitro and in clinical practice with regard to the following spectrum of microorganisms:

- aerobic Gram-positive microorganisms: Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae;

- aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella (Branhamella) catarrhalis;

- mycobacteria: complex Mycobacterium avium (MAC), consisting of Mycobacterium avium, Mycobacterium intracellulare;

- Mycoplasma: Mycoplasma pneumoniae;

- other microorganisms: Chlamydia pneumoniae.

In the following combinations is active in vitro and in clinical practice in relation to Helicobacter pylori:

- combined therapy with two drugs: omeprazole and clarithromycin; lansoprazole and clarithromycin;

- combined therapy with three drugs: lansoprazole, clarithromycin and amoxicillin; omeprazole, clarithromycin and amoxicillin.

Also clarithromycin has an effect in vitro for most strains of the following microorganisms (however, the safety and efficacy of clarithromycin in clinical practice has not been confirmed by clinical studies and the practical significance remains unclear):

- aerobic Gram-positive microorganisms: Streptococcus agalactiae, Streptococcus spp. group viridans, Streptococci (groups C, F, G);

- aerobic gram-negative microorganisms: Bordetella pertussis, Legionella pneumophila, Pasteurella multocida;

- anaerobic Gram-positive microorganisms: Clostridium perfringes, Peptococcus niger, Propionibacterium acnes;

- anaerobic gram-negative microorganisms: Prevotella melaninogenica (formerly Bacteroides melaninogenicus).

The metabolite of clarithromycin 14-hydroxyclarithromycin also has a therapeutically significant antimicrobial activity.

Pharmacokinetics:

Clarithromycin is rapidly and actively absorbed when ingested, its bioavailability is approximately 50%. The connection with plasma proteins is 65-75%.

After oral administration of 20-30% of the received dose of clarithromycin is rapidly hydroxylated in the liver by isoenzymes CYP3A4, CYP3A5 and CYP3A7 with the formation of the main metabolite - 14 (R) -hydroxyclaryl thromycin, which has a pronounced antimicrobial activity against Haemophilus influenzae. It is an inhibitor of the isoenzymes CYP3A4, CYP3A5 and CYP3A7. Clarithromycin and its 14-hydroxymetabolite is rapidly distributed across all tissues and body fluids. After oral administration, the concentration of clarithromycin in tissues (especially in the lungs) is several times higher than in plasma. The intake of food immediately before the administration of the drug slightly slows the onset of absorption of clarithromycin, but does not affect its bioavailability and the formation of the active metabolite of 14-hydroxyclarithromycin. In this way, clarithromycin can be used regardless of the meal.

Clarithromycin and 14-hydroxyclarithromycin do not cumulate.

When the drug is prescribed twice a day for 250 mg, the maximum equilibrium concentration (C_mOh) of clarithromycin in plasma was achieved after 2-3 days and averaged 1 μg / ml for clarithromycin and 0.6 μg / ml for 14-hydroxyclarithromycin, with half-lives of the starting compound and its metabolite 3-4 and 5-6 hours respectively.

When prescribing the drug 2 times a day for 500 mg of equilibrium C_mOh clarithromycin and its hydroxylated metabolite in plasma averaged 2.7-2.9 μg / ml and 0.88-0.83 μg / ml, respectively. The half-life of the starting compound with a dose of 500 mg was 5-7 hours, whereas for 14-hydroxycyl-rhythomycin this value was 7-9 hours.

After the administration of higher doses of clarithromycin, a further increase in C_mOh and the duration of the half-life, which indicates a nonlinear character of the pharmacokinetics of clarithromycin.

It is excreted by the kidneys and intestines (20-30% - in unchanged form, the rest - in the form of metabolites). With a single admission, 37% of the kidneys and 40% of the intestines are excreted.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to clarithromycin:

- infections of the lower respiratory tract (eg, acute and chronic bronchitis, pneumonia);

- infections of the upper respiratory tract (eg, sinusitis and pharyngitis);

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

- disseminated or localized mycobacterial infections caused, Mycobacterium avium and Mycobacterium intracellulare;

- Clarithromycin used to prevent dissemination of infection caused by the complex Mycobacterium avium (MAC), An HIV-infected patient with a CD4 + -lymphocytes (T-helper lymphocytes) no more than 100 in 1 mm³;

- Clarithromycin indicated for eradication H. pylori (as part of a combined therapy) and reducing the frequency of recurrences of duodenal ulcers.

Contraindications:

- Hypersensitivity to antibiotics of macrolides; -hypersensitivity to the components of the drug;

- simultaneous administration of astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, midazolam for oral ingestion, alprazolam, triazolam (see also section "Interaction with other medicinal products"). In patients taking these drugs concomitantly with clarithromycin, there is an increase in their concentration in the blood. It is possible to prolong the QT interval and develop cardiac arrhythmias, including ventricular paroxysmal tachycardia, ventricular fibrillation, and ventricular flutter;

- porphyria;

- lactation period;

- Children under 12 years of age (due to the impossibility of adequate dose selection).

Carefully:

Renal and / or hepatic insufficiency, myasthenia gravis, simultaneous administration of medicinal products, metabolized by the liver, simultaneous reception of colchicine, pregnancy.

Pregnancy and lactation:

The safety of clarithromycin during pregnancy and during breastfeeding has not been established. Therefore, the drug Clarithromycin during pregnancy is possible only if there are clear indications and only if the intended benefit to the mother exceeds the potential risk to the fetus.

Clarithromycin penetrates into breast milk, so breastfeeding should be stopped during lactation because of the potential for serious adverse reactions in infants.

Dosing and Administration:

The drug is taken orally, regardless of food intake.

Pharyngitis or tonsillitiscaused by S. Pyogenes - 250 mg twice a day for 10 days.

Acute Sinusitis, caused by N. Influenzae, M. Catarrhalis, S. Pneumoniae - 500 mg twice a day for 14 days.

Exacerbation of chronic bronchitis, caused by:

- N. Influenzae - 500 mg twice a day for 7-14 days;

- H. Parainfluenzae - 500 mg twice a day for 7 days;

- M. Catarrhalis, S. Pneumoniae - 250 mg twice a day for 7-14 days.

Community-acquired pneumonia, caused by:

- N. Influenzae; N.Parainfluenzae, M. catarrhalis - 250 mg twice a day for 7 days;

- S. Pneumoniae - 250 mg twice a day for 7-14 days;

- C. Pneumoniae - 250 mg twice a day for 7-14 days.

Uncomplicated skin and soft tissue infections, caused by S. Aureus, S. Pyogenes - 250 mg twice a day for 7-14 days.

With infectious diseases caused by mycobacteria

the recommended initial dose is 500 mg twice a day. Treatment should continue as long as there are clinical and microbiological evidence of its effectiveness. Clarithromycin should be used in combination with other antimicrobial agents.

For eradication of H. pylori

Combination treatment with three drugs

- Clarithromycin 500 mg twice a day in combination with lansoprazole 30 mg twice a day and amoxicillin 1000 mg twice a day for 10-14 days;

- Clarithromycin 500 mg twice a day in combination with amoxicillin 1000 mg twice a day and omeprazole 20 mg twice a day for 10 days.

In patients with gastric ulcer diagnosed at the time of initiation of therapy, the administration of omeprazole 20 mg once daily for an additional 18 days is recommended for ulcer healing and relief of symptoms.

Combination treatment with two drugs

- Clarithromycin 500 mg 3 times a day in combination with omeprazole at a dose of 40 mg / 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 in combination with lansoprazole at a dose of 60 mg / day for 14 days. To fully heal the ulcer, an additional decrease in the acidity of the gastric juice may be required.

In chronic renal failure (CRF)

Patients with a creatinine clearance (CK) of less than 30 ml / min are given one half of the usual dose of the drug Clarithromycin or increase the intervals between taking drugs twice.

With hepatic insufficiency

When using the drug Clarithromycin Care should be taken in patients with hepatic insufficiency. However, while maintaining normal kidney function in patients with moderate or severe hepatic insufficiency, dose adjustment Clarithromycin not required.

Elderly age

Dose reduction for the elderly is not required.

Dosing and Administration in Children

Application of the drug Clarithromycin in children under 12 years of age or with a body weight of less than 33 kg is contraindicated.

In children older than 12 years, the drug is used in the same doses as in adults.

Side effects:

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

From the digestive system: dyspepsia, nausea, vomiting, gastralgia, diarrhea, stomatitis, glossitis, candidiasis of the oral mucosa, discoloration of the tongue and teeth, increased activity of "liver" transaminases, hepatocellular and cholestatic hepatitis, cholestatic jaundice, pseudomembranous colitis, acute pancreatitis, hepatic impairment with a fatal outcome mainly on the background of severe co-morbidities and / or concomitant drug therapy.

From the side of the cardiovascular system (SSS): ventricular tachycardia, incl. type "pirouette", flutter and ventricular fibrillation, prolongation of the QT interval on the ECG.

From the sense organs: noise, ringing in the ears, change in taste (dysgeusia), uveitis, hearing loss, which occurs after the drug has been discontinued, impaired sense of smell.

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

From the side of the urinary system: interstitial nephritis.

Laboratory indicators: leukopenia, hypercreatininaemia, hypoglycemia (including with the simultaneous use of hypoglycemic drugs).

Allergic reactions: skin rash, itching, urticaria, skin hyperemia, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis, angioedema, anaphylactic reactions.

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

Overdose:

Symptoms: abdominal pain, nausea, vomiting, diarrhea. There is a report of one patient with bipolar disorder who took 8 g of clarithromycin. The patient had the following symptoms: impairment of mental status, paranoid behavior, hypokalemia and hypoxemia.

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

Interaction:

With concurrent administration of clarithromycin and medications,primarily metabolized by CYP3A isoenzymes, there may be a mutual increase in their concentrations, which may enhance or prolong both the therapeutic and side effects.

Contraindicated simultaneous administration with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, alprazolam, midazolam, triazolam.

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

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

When used simultaneously with ergotamine and dihydroergotamine, acute drug poisoning of the groupergotamine (vascular spasm, ischemia of limbs and other tissues, including the central nervous system).

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

With the simultaneous administration of fluconazole at a dose of 200 mg daily and clarithromycin at a dose of 1 g / day, it is possible to increase the equilibrium concentration (Css) and the area under the concentration-time curve (AUC) of clarithromycin by 33% and 18%, respectively. Correction of the dose of clarithromycin is not required.

With the simultaneous administration of ritonavir 600 mg / day and clarithromycin 1 g / day, a decrease in the metabolism of clarithromycin (an increase in C_mOh by 31%, Css by 182% and AUC by 77%), complete suppression of the formation of 14-hydroxyclarithromycin. In patients with CRF, dose adjustment is necessary: with a QC of 30-60 ml / min, the dose of clarithromycin should be reduced by 50%, with a CK of less than 30 ml / min by 75%. Ritonavir Do not take concomitantly with clarithromycin at a dose exceeding 1 g / day.

With simultaneous administration with quinidine and disopyramide, ventricular tachycardia such as pirouette may occur.It requires ECG monitoring (increasing the QT interval), serum concentrations of these drugs. Clarithromycin increases the concentration of HMG-CoA reductase inhibitors (lovastatin, simvastatin), which is associated with a risk of rhabdomyolysis.

With the use of clarithromycin and omeprazole, Cmax, AUC and T1 / 2 omeprazole can increase by 30%, 89% and 34%, respectively. The average pH value in the stomach for 24 hours was 5.2 when taking only omeprazole and 5.7 when taking omeprazole together with clarithromycin.

With the use of clarithromycin and indirect anticoagulants, the effect of the latter is possible.

When using clarithromycin with sildenafil, tadalafil or vardenafil (phosphodiesterase-5 inhibitors (PDE5)), it is possible to increase the inhibitory effect on PDE. It may be necessary to reduce the dose of PDE5 inhibitors.

With the simultaneous use of clarithromycin with theophylline and carbamazepine, an increase in the concentration of the latter in the systemic circulation is possible.

When using clarithromycin with tolterodine in patients with low activity of the CYP2D6 isoenzyme, a dose reduction of tolterodine in the presence of clarithromycin (inhibitor of CYP3 A isoenzymes) may be required.

With concurrent administration of clarithromycin (1 g / day) with midazolam (oral), augmentation of the midazolam AUC is possible 7-fold. It is necessary to avoid the combined oral administration of clarithromycin and midazolam, and other benzodiazepines, which are metabolized by isoenzymes of CUR3A (triazolam and alprazolam). When using midazolam (intravenous) and clarithromycin, a dose adjustment may be required. The same precautions should be applied to other benzodiazepines, which are metabolized by CYP3A isoenzymes. For benzodiazepines, the removal of which does not depend on CYP3A isozymes (temazepam, nitrazepam, lorazepam), clinically significant interaction with clarithromycin is unlikely.

When taking clarithromycin with colchicine, the effect of colchicine may be enhanced.

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

With the simultaneous administration of clarithromycin and digoxin, the concentration of digoxin in the serum should be carefully monitored (possibly increasing its concentration and the development of potentially fatal arrhythmias).

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

When the drug is taken together clarithromycin (1 g / day) and atazanavir (400 mg / day), augmentation of Atazanavir AUC by 28%, clarithromycin 2-fold, reduction of AUC of 14-hydroxyclarithromycin by 70% is possible. In patients with KK 30-60 ml / min, the dose of clarithromycin should be reduced by 50%. Clarithromycin in doses exceeding 1 g / day can not be administered together with protease inhibitors.

With the simultaneous administration of clarithromycin and itraconazole, a mutual increase in the concentration of drugs in the plasma is possible. For patients who simultaneously take itraconazole and clarithromycin, careful monitoring is necessary because of the possible enhancement or extension of the pharmacological effects of these drugs.

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

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

Special instructions:

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

Use with caution in combination with drugs metabolized by the liver (it is recommended to monitor their concentration in the blood).

In the case of concomitant use with warfarin or other indirect anticoagulants, prothrombin time should be monitored.

With heart disease in the anamnesis, simultaneous administration with terfenadine, cisapride, astemizole is not recommended.

It is necessary to pay attention to the possibility of cross-resistance between clarithromycin and other antibiotics from the macrolide group, as well as lincomycin and clindamycin.

Prolonged or repeated use of the drug Clarithromycin can lead to the development of resistant microflora (bacterial or fungal).When developing a secondary infection, it is necessary to stop taking the drug Clarithromycin. The appointment of adequate therapy is necessary.

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

In a small number of patients, carriers H. pylori, can develop resistance to drug Clarithromycin.

Effect on the ability to drive transp. cf. and fur:

Reception of the drug Clarithromycin may be accompanied by dizziness and other undesirable reactions from the central nervous system, and therefore care should be taken when driving vehicles or complex equipment.

Form release / dosage:Film coated tablets, 250 mg and 500 mg.

Packaging:7 tablets in a blister of two-layer PVC / PVDC / film and aluminum foil.

2 blisters together with instructions for use in a cardboard bundle.

Storage conditions:In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:PL-000737

Date of registration:29.09.2011

The owner of the registration certificate:Aurobindo Pharma Co., Ltd.Aurobindo Pharma Co., Ltd. India

Manufacturer: & nbsp

AUROBINDO PHARMA, Ltd. India

Representation: & nbspAurobindo Pharma, ZAOAurobindo Pharma, ZAO

Information update date: & nbsp27.08.2013

Illustrated instructions

Instructions

Clarithromycin (Clarithromycin)