Clarithromycin-Vertex, 250 mg capsules 14 pcs

Otitis, Angina, Colds, Gastric and duodenal ulcers, Bronchitis, Respiratory tract infections, Sinusitis, GI infections caused by Helicobacter pylori, Tonsillitis, Boils, Skin infections, Pharyngitis

Infectious and inflammatory diseases caused by clarithromycin-sensitive microorganisms:

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

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

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

– Disseminated or localized mycobacterial infections caused by Mycobacterium avium and Mycobacterium intracellulare; localized infections caused by Mycobacterium chelonae, Mycobacterium fortuitum, and Mycobacterium kansasii;

– Preventing the spread of infection caused by Mycobacterium avium complex (MAC) in HIV-infected patients with CD4 (Tcheloper lymphocyte) counts of 100 or less in 1 mm3;

– Eradication of H. pylori and reduced recurrence rate of duodenal ulcer;

– Odontogenic infections.

Active ingredient

Composition

Composition per tablet

Active ingredient:

Clarithromycin in terms of 100% anhydrous substance – 250.0 mg.

Auxiliary substances: Potato starch – 46.0 mg, microcrystalline cellulose – 75.0 mg, povidone K17 (polyvinylpyrrolidone low molecular weight medical 12600 ± 2700) – 40.0 mg, pregelatinized starch (starch1500) – 30.0 mg, colloidal silicon dioxide (aerosil) – 4.5 mg, magnesium stearate – 4.5 mg.

The shell: Opadray II (polyvinyl alcohol, partially hydrolyzed – 8.000 mg, macrogol (polyethylene glycol 3350) – 4.040 mg, talc – 2.960 mg, titanium dioxide E171 – 4.374 mg, quinoline yellow E104 aluminum varnish – 0,602 mg, iron oxide II dye E172 – 0.006 mg, sunset yellow aluminum varnish E110 – 0.014 mg, indigo carmine aluminum varnish E132 – 0.004 mg).

How to take, the dosage

For oral administration. Regardless of meals.

Adults and children over 12 years of age – 1 tablet (250 mg) 2 times a day.

In case of more severe infections, the dose is increased to 500 mg twice a day.

The usual duration of treatment is 5 to 14 days.

The exceptions are community-acquired pneumonia and sinusitis, which require 6 to 14 days of treatment.

Doses for treatment of mycobacterial infections other than tuberculosis:

The recommended dose for mycobacterial infections is clarithromycin 500 mg twice daily.

The treatment of disseminated MAC infections in patients with AIDS should be continued as long as there is clinical and microbiological efficacy. Clarithromycin should be administered in combination with other antimicrobials active against these pathogens. The duration of treatment of other non-tuberculous mycobacterial infections is determined by the physician.

For prevention of infections caused by MAC:

The recommended dose of clarithromycin for adults is 500 mg twice daily.

For odontogenic infections, the dose of clarithromycin is 250 mg (1 tablet) 2 times a day for 5 days.

For eradication of H. pylori:

In patients with peptic ulcer disease caused by H. pylori infection, clarithromycin may be administered at 500 mg twice daily in combination with other antimicrobials and proton pump inhibitors for 7-14 days, according to national and international guidelines for the treatment of H. pylori infection.

Patients with renal impairment

Patients with creatinine clearance less than 30 mL/min are prescribed half the usual dose of clarithromycin, i.e. 250 mg (1 tablet) once daily or, for more severe infections, 1 tablet (250 mg) 2 times daily. Treatment of such patients is continued for no more than 14 days.

Interaction

Hepatic dysfunction (increased hepatic enzyme activity in the blood, hepatocellular and/or cholestatic hepatitis with or without jaundice) has been reported with clarithromycin. Liver dysfunction can be severe, but is usually reversible. There are cases of hepatic failure with fatal outcome, mainly associated with the presence of serious comorbidities and/or concomitant use of other drugs. In case of signs and symptoms of hepatitis, such as anorexia, jaundice, darkened urine, itching, abdominal pain on palpation, clarithromycin therapy should be stopped immediately.

In the presence of chronic liver disease, serum enzyme activity should be monitored regularly.

When treated with almost all antibacterials, including clarithromycin, there have been cases of pseudomembranous colitis, the severity of which may vary from mild to life-threatening. Cases of Clostridium difficile-associated diarrhea, the severity of which can range from mild to life-threatening colitis, have been described with virtually all antibacterials, including clarithromycin. Antibacterials can alter the normal gut microflora, which can lead to growth of C. difficile. Pseudomembranous colitis caused by Clostridium difficile should be suspected in all patients who develop diarrhea after using antibacterials. Cases of pseudomembranous colitis developed 2 months after antibiotic use have been described.

Long-term antibiotic use may lead to colonies with increased numbers of insensitive bacteria and fungi. In case of superinfection, appropriate therapy should be prescribed. After a course of antibiotic therapy, close medical follow-up of the patient is necessary.

When treated with macrolides, including clarithromycin, prolongation of cardiac repolarization and QT interval have been observed, causing risk of cardiac arrhythmias and pirouette-type ventricular tachycardia (see section “Adverse effects”). Because the following situations may increase the risk of ventricular arrhythmias (including pirouette-type ventricular tachycardia),

– Clarithromycin should not be used in the following patient categories:

– in patients with hypokalemia (see “Contraindications” section);

– simultaneous administration of clarithromycin with astemizole, cisapride, pimozide, and terfenadine is contraindicated (see

Patients with a history of congenital or acquired registered QT interval prolongation or ventricular arrhythmias are contraindicated.

– clarithromycin should be used with caution in the following categories of patients:

– in patients with coronary heart disease (CHD), severe heart failure, conduction abnormalities, or clinically significant bradycardia;

– in patients with electrolyte disturbances such as hypomagnesemia;

– in patients concomitantly taking other medications associated with QT interval prolongation (see

Patients who are concomitantly taking other drugs associated with QT interval prolongation (see section “Interaction with other medicinal products”).

The development of cross-resistance to clarithromycin and other antibiotics of the macrolide group, as well as to lincomycin and clindamycin is possible.

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

Mild to moderate skin and soft tissue infections are most commonly caused by Staphylococcus aureus and Streptococcus pyogenes. Both pathogens may be resistant to macrolides. Therefore, it is important to test for sensitivity.

Macrolides can be used for infections caused by Corynebacterium minutissimum (erythrasma), common acne and rye, and in situations where penicillin cannot be used.

In case of acute hypersensitivity reactions such as anaphylactic reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), clarithromycin should be stopped immediately and appropriate therapy should be started.

If used together with warfarin or other indirect anticoagulants, the INR and prothrombin time should be monitored.

Influence on driving and operating ability

There are no data on the effect of clarithromycin on driving and operating ability.

Caution should be exercised when driving vehicles and operating machinery, given the potential for dizziness, vertigo, confusion, and disorientation that may occur with this drug.

When taking saquinavir with ritonavir, the potential effect of ritonavir on clarithromycin should be considered.

Special Instructions

Hepatic dysfunction (increased hepatic enzyme activity in the blood, hepatocellular and/or cholestatic hepatitis with or without jaundice) has been reported with clarithromycin. Liver dysfunction can be severe, but is usually reversible. There are cases of hepatic failure with fatal outcome, mainly associated with the presence of serious comorbidities and/or concomitant use of other drugs. In case of signs and symptoms of hepatitis, such as anorexia, jaundice, darkened urine, itching, abdominal pain on palpation, clarithromycin therapy should be stopped immediately.

In the presence of chronic liver disease, serum enzyme activity should be monitored regularly.

When treated with almost all antibacterials, including clarithromycin, there have been cases of pseudomembranous colitis, the severity of which may vary from mild to life-threatening. Cases of Clostridium difficile-associated diarrhea, the severity of which can range from mild to life-threatening colitis, have been described with virtually all antibacterials, including clarithromycin. Antibacterials can alter the normal gut microflora, which can lead to growth of C. difficile. Pseudomembranous colitis caused by Clostridium difficile should be suspected in all patients who develop diarrhea after using antibacterials. Cases of pseudomembranous colitis developed 2 months after antibiotic use have been described.

Long-term antibiotic use may lead to colonies with increased numbers of insensitive bacteria and fungi. In case of superinfection, appropriate therapy should be prescribed. After a course of antibiotic therapy, close medical follow-up of the patient is necessary.

When treated with macrolides, including clarithromycin, prolongation of cardiac repolarization and QT interval have been observed, causing risk of cardiac arrhythmias and pirouette-type ventricular tachycardia (see section “Adverse effects”). Because the following situations may increase the risk of ventricular arrhythmias (including pirouette-type ventricular tachycardia),

– Clarithromycin should not be used in the following patient categories:

– in patients with hypokalemia (see “Contraindications” section);

– simultaneous administration of clarithromycin with astemizole, cisapride, pimozide, and terfenadine is contraindicated (see

Patients with a history of congenital or acquired registered QT interval prolongation or ventricular arrhythmias are contraindicated.

– clarithromycin should be used with caution in the following categories of patients:

– in patients with coronary heart disease (CHD), severe heart failure, conduction abnormalities, or clinically significant bradycardia;

– in patients with electrolyte disturbances such as hypomagnesemia;

– in patients concomitantly taking other medications associated with QT interval prolongation (see

Patients who are concomitantly taking other drugs associated with QT interval prolongation (see section “Interaction with other medicinal products”).

The development of cross-resistance to clarithromycin and other antibiotics of the macrolide group, as well as to lincomycin and clindamycin is possible.

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

Mild to moderate skin and soft tissue infections are most commonly caused by Staphylococcus aureus and Streptococcus pyogenes. Both pathogens may be resistant to macrolides. Therefore, it is important to test for sensitivity.

Macrolides can be used for infections caused by Corynebacterium minutissimum (erythrazma), common acne and rye, and in situations where penicillin cannot be used.

In case of acute hypersensitivity reactions such as anaphylactic reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), clarithromycin should be stopped immediately and appropriate therapy should be started.

If used together with warfarin or other indirect anticoagulants, the INR and prothrombin time should be monitored.

Influence on driving and operating ability

There are no data on the effect of clarithromycin on driving and operating ability.

Caution should be exercised when driving vehicles and operating machinery, given the potential for dizziness, vertigo, confusion, and disorientation that may occur with this drug.

Contraindications

Concomitant use of clarithromycin with colchicine (see section “Interaction with other medicinal products”).

– Concomitant use of clarithromycin with ticagrelor or ranolazine.

– History of QT interval prolongation (congenital or acquired registered QT interval prolongation) or ventricular arrhythmias, including pirouette-type ventricular tachycardia (see sections “Special Considerations” and “Interaction with Other Medications”).

– Hypokalemia (risk of QT interval prolongation).

– Severe hepatic impairment concomitant with renal impairment.

– A history of cholestatic jaundice/hepatitis developed with clarithromycin (see section “Special Precautions”).

– Porphyria.

– The period of breastfeeding.

– Age under 12 years (effectiveness and safety not established).

With caution

– Moderate to severe renal failure.

– Moderate to severe hepatic insufficiency.

– Concomitant administration of clarithromycin with benzodiazepines such as alprazolam, triazolam, midazolam for intravenous use or for application to the oral mucosa (see section “Interaction with other medicinal products”).

– Concomitant administration with drugs that are metabolized by the CYP3A isoenzyme, e.g., carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants (e.g., warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine (see “Interaction with other drugs. section “Interaction with other medicinal products”).

– Concomitant use with drugs that induce CYP3A4 isoenzyme, such as rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort (see section “Interaction with other medicinal products”).

– Concomitant administration of clarithromycin with statins that do not depend on CYP3A isoenzyme metabolism (e.g., fluvastatin) (see section “Interaction with other medicinal products”).

– Concomitant use with “slow” calcium channel blockers that are metabolized by CYP3A4 isoenzyme (e.g., verapamil, amlodipine, diltiazem).

– Patients with coronary heart disease (CHD), severe heart failure, hypomagnesemia, conduction abnormalities or clinically significant bradycardia, and patients taking class IA (quinidine, procainamide) and class III (dofetilide, amiodarone, sotalol) antiarrhythmic drugs simultaneously.

– Pregnancy.

Side effects

Classification of adverse reactions by frequency of development (number of reported cases/number of patients): very common (≥1/10), common (≥1/100, < 1/10), infrequent (≥1/1000, < 1/100), frequency unknown (adverse effects from post-marketing experience; frequency cannot be estimated based on available data).

Allergic reactions

Often: rash.

Infrequent: hypersensitivity, itching, urticaria.

Frequent unknown: anaphylactic reaction, angioneurotic edema, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptomatology (DRESS syndrome).

Nervous system disorders

Often: headache, insomnia.

Infrequently: dizziness, somnolence, tremor, anxiety.

Frequent unknown: seizures, psychotic disorders, confusion, depersonalization, depression, disorientation, hallucinations, dream disorders (“nightmares” dreams), paresthesia, mania.

Skin disorders

Often: intense sweating.

Prevalence unknown: acne.

Urinary system disorders

Prevalence unknown: renal failure, interstitial nephritis.

Metabolism and nutrition disorders

Infrequent: anorexia, decreased appetite.

Musculoskeletal disorders

Infrequent unknown: myopathy.

Digestive system disorders

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

Infrequent: gastritis, stomatitis, glossitis, bloating, constipation, dry mouth, belching, flatulence, cholestasis, hepatitis including cholestatic or hepatocellular.

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

Sensory organs

Often: dysgeusia, perversion of taste.

Infrequent: vertigo, hearing impairment, tinnitus.

Frequent unknown: deafness, agueusia (loss of taste), parosmia, anosmia.

Cardiovascular system disorders

Infrequent: prolongation of the QT interval on the electrocardiogram, sensation of palpitation.

Frequent unknown: ventricular tachycardia, including pirouette type, ventricular fibrillation, bleeding.

Laboratory findings

Often: abnormality in hepatic sample.

Infrequent: leukopenia, neutropenia, eosinophilia, increased activity of: alanine aminotransferase (ALT), aspartate aminotransferase (ACT), gammaglutamyltransferase (GGTP), alkaline phosphatase, lactate dehydrogenase (LDH).

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

General disorders

Infrequent: malaise, asthenia, chest pain, chills, fatigue.

Infectious and parasitic diseases

Infrequent: candidiasis.

Infrequent unknown: pseudomembranous colitis, rye.

Patients with suppressed immunity

In patients with AIDS and other immunodeficiencies who receive clarithromycin at higher doses for long term treatment of mycobacterial infections, it is often difficult to distinguish adverse effects of the drug from symptoms of HIV infection or comorbidities.

The most common adverse events in patients taking a daily dose of clarithromycin equal to 1000 mg were: nausea, vomiting, perversion of taste, abdominal pain, diarrhea, rash, flatulence, headache, constipation, hearing loss, and increased ACT and ALT activity in the blood. Adverse events with low frequency of occurrence, such as dyspnea, insomnia, and dry mouth, have also been reported.

In patients with suppressed immunity, laboratory parameters were evaluated by analyzing their significant deviations from the norm (sharp increase or decrease). Based on this criterion, 2-3% of patients who received clarithromycin at a dose of 1000 mg daily registered a significant increase in ACT and ALT activity in the blood, as well as a decrease in leukocyte and platelet counts. A small number of patients also reported increases in residual nitrogen, urea concentrations.

Overdose

Symptoms. Large doses of clarithromycin may cause gastrointestinal symptoms.

One patient with a history of bipolar disorder has described mental status changes, paranoid behavior, hypokalemia and hypoxemia after taking 8 g of clarithromycin.

Treatment. In case of overdose, the unabsorbed drug should be removed from the gastrointestinal tract (gastric lavage, administration of activated charcoal, etc.) and symptomatic therapy should be carried out. Hemodialysis and peritoneal dialysis have no significant effect on serum concentrations of clarithromycin, as is the case with other macrolide drugs.

Pregnancy use

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

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

Clarithromycin is excreted with the breast milk. Breast-feeding should be discontinued if administration during lactation is necessary.

Similarities