Clarithromycin SR-Vertex, 500 mg 14 pcs

Pharyngitis, Chlamydia, Lung inflammation (pneumonia), Sinusitis, Bronchitis, Skin infections, Otitis media, Gastrointestinal infections

Infectious and inflammatory diseases caused by clarithromycin-sensitive microorganisms:

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

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

– infections of the skin and soft tissues (such as folliculitis, inflammation of the subcutaneous tissue, rye).

Active ingredient

Composition

Long-acting, film-coated tablets

1 film-coated, long-acting tablet contains:

active ingredient:

clarithromycin 500,000 mg;

excipients:

Hypromellose 2208 (100 mPa-s) 200,000 mg,

Hypromellose 2910 (50 mPas-c) 150,000 mg,

Microcrystalline cellulose 137,500 mg,

colloidal silicon dioxide 2.500 mg,

magnesium stearate 10.000 mg;

film coating:

[hypromellose 2910 (6 mPa-s) 15.000 mg, hyprolose (hydroxypropyl cellulose) 5.820 mg, talc 5.778 mg, titanium dioxide 3.261 mg, iron oxide yellow (iron oxide) 0.141 mg] or [dry film coating mixture, containing hypromellose 2910 (6 mPa-s) (50%), hyprolose (hydroxypropyl cellulose) (19.4%), talc (19.26%), titanium dioxide (10.87%), iron oxide yellow (iron oxide) (0.47%)] 30,000 mg.

How to take, the dosage

Ingestion.

The tablets of Clarithromycin SR must not be crushed or chewed; they must be swallowed whole.

Adults and children over 12 years of age: 1 tablet (500 mg) once daily with meals.

In severe infections, the dose is increased to 2 tablets (1000 mg) once daily with meals.

The usual duration of treatment is 5-14 days.

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

Renal dysfunction

In patients with severe renal impairment (CKR less than 30 ml/min) clarithromycin is contraindicated. In patients with moderate renal impairment (CKD 30 to 60 ml/min) the dose is halved. Maximum daily dose is 500 mg (1 tablet).

Interaction

The following drugs are contraindicated with clarithromycin due to the possibility of serious side effects./u>

Cisapride, pimozide

Combined use may: Increased cisapride/pimozide concentrations, increased QT interval, occurrence of cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, pirouette-type ventricular tachycardia.

Terfenadine and astemizole

When used together it is possible: Increased terfenadine/astemizole blood concentrations, occurrence of cardiac arrhythmias, increased QT interval, ventricular tachycardia, ventricular fibrillation and pirouette-type ventricular tachycardia.

Alkaloids of ergot

Postmarketing studies indicate that the following effects associated with acute poisoning with ergotamine or dihydroergotamine are possible when clarithromycin is coadministered vascular spasm, ischemia of extremities and other tissues, including the central nervous system. Concomitant use of clarithromycin and ergot alkaloids is contraindicated (see section “Contraindications”).

Effects of other drugs on clarithromycin

The following drugs have proven or suspected effects on clarithromycin concentrations. If they are used together with clarithromycin, doses may need to be adjusted or alternative treatment may be necessary.

Drugs that are inducers of the CYP3A isoenzyme (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort) may induce the metabolism of clarithromycin. This can lead to subtherapeutic concentrations of clarithromycin, resulting in decreased efficacy. In addition, plasma concentration of CYP3A isoenzyme inducer should be monitored, which may increase due to inhibition of CYP3A isoenzyme by clarithromycin. When rifabutin and clarithromycin are used together, there was an increase in plasma concentration of rifabutin and a decrease in plasma concentration of clarithromycin with an increased risk of uveitis.

Efavirenz, nevirapine, rifampicin, rifabutin, rifapentin

. Strong cytochrome P450 inducers such as efavirenz, nevirapine, rifampicin, rifabutin and rifapentine can accelerate the metabolism of clarithromycin and thus decrease the plasma concentration of clarithromycin and weaken the therapeutic effect, and at the same time increase the concentration of 14-OH clarithromycin, a metabolite that is also microbially active.

Because the microbiological activity of clarithromycin and 14-OH clarithromycin is different for different bacteria, the therapeutic effect may be reduced when clarithromycin and enzyme inducers are used together.

Etravirin

The concentration of clarithromycin is decreased when using etravirin, but the concentration of the active metabolite 14-OH-clarithromycin is increased. Because 14-OH clarithromycin has low activity against MAC infections, the overall activity against these pathogens may change, so alternative treatments should be considered for the treatment of MAC.

Oral hypoglycemic agents/insulin

The co-administration of clarithromycin and oral hypoglycemic agents and/or insulin may cause severe hypoglycemia. Co-administration of clarithromycin and some glucose-lowering drugs such as nateglinide, pioglitazone, repaglinide and rosiglitazone may result in inhibition of CYP3A isoenzyme by clarithromycin, which may lead to hypoglycemia. Close monitoring of glucose concentration is recommended.

Fluconazole

. Co-administration of fluconazole at a dose of 200 mg daily and clarithromycin at a dose of 500 mg twice daily in 21 healthy volunteers resulted in a 33% and 18% increase in the minimum mean equilibrium concentration (Cssmin) and AUC of clarithromycin, respectively. However, co-administration had no significant effect on the mean equilibrium concentration of the active metabolite 14-OH-clarithromycin. No dose adjustment of clarithromycin is required for concomitant administration of fluconazole.

Ritonavir

Pharmacokinetic study showed that co-administration of ritonavir at a dose of 200 mg every eight hours and clarithromycin at a dose of 500 mg every 12 hours resulted in a marked inhibition of clarithromycin metabolism. When ritonavir was coadministered, the Cmax of clarithromycin increased by 31%, the Cmin increased by 182%, and the AUC increased by 77%. Complete inhibition of 14-OH-clarithromycin formation was observed. Due to the wide therapeutic range of clarithromycin, no dose reduction is required in patients with normal renal function. In patients with renal impairment, it is advisable to consider the following dose adjustments: for CKD 30-60 ml/min, the clarithromycin dose should be reduced by 50% (no more than one Clarithromycin SR tablet per day). Patients with severe renal impairment (CK < 30 ml/min) should not take Clarithromycin SR due to the inability to adequately adjust (reduce) the dose (see section “Contraindications”), In such patient groups, normal-release clarithromycin tablets can be used. Ritonavir should not be coadministered with clarithromycin in doses greater than 1 g/day.

Effects of clarithromycin on other drugs

Antiarrhythmic drugs (quinidine and disopyramide)

Special Instructions

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

The prolonged use of antibiotics can lead to colonies with increased numbers of insensitive bacteria and fungi. Appropriate therapy should be prescribed if superinfection occurs.

Hepatic dysfunction (increased activity of “hepatic” enzymes in the blood plasma, hepatocellular and/or cholestatic hepatitis with or without jaundice) has been reported when using clarithromycin.

Hepatic dysfunction can be severe, but is usually reversible. There are cases of fatal hepatic failure, mostly related to the presence of serious comorbidities and/or concomitant use of other medications. 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, regular monitoring of plasma enzyme activity is necessary.

Antibacterial drugs can change the normal intestinal microflora, which can lead to the growth of C. difficile. Pseudomembranous colitis caused by Clostridium difficile should be suspected in all patients who experience the appearance of diarrhea after using antibacterials.

After a course of antibiotic therapy, careful medical follow-up of the patient is necessary. Cases of pseudomembranous colitis have been described 2 months after antibiotic treatment.

Clarithromycin should be used with caution in patients with CHD, severe heart failure, hypomagnesemia, severe bradycardia (less than 50 bpm), and concomitant use with class IA antiarrhythmic drugs (quinidine, procainamide) and class III (dofetilide, amiodarone, sotalol). In these conditions and if clarithromycin is concomitantly administered with these drugs, the electrocardiogram should be monitored regularly for QT interval prolongation.

Cross-resistance to clarithromycin and other macrolide antibiotics and to lincomycin and clindamycin may develop.

In view of the increasing resistance of Streptococcus pneumoniae to macrolides, it is important to conduct sensitivity testing when using clarithromycin in 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 can be resistant to macrolides. Therefore, it is important to give a sensitivity test.

Macrolides can be used for infections caused by Corynebacterium minutissimum (erythrasma), acne vulgaris 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), Schoenlein-Henoch purpura, clarithromycin should be stopped immediately and appropriate therapy should be started.

A worsening of symptoms of myasthenia gravis has been reported in patients taking clarithromycin.

In case of co-administration with warfarin or other indirect anticoagulants, the INR and prothrombin time should be monitored (see section “Interaction with other medicinal products”).

Contraindications

Ensensitivity to clarithromycin, other drug components and other macrolides;

Concomitant administration of clarithromycin with astemizole, cisapride, pimozide, terfenadine (see “Interaction with other drugs.

– concomitant use of clarithromycin with cysticazole, cisapride, simozide, terfenadine (see section “Interaction with other medicinal products”);

– severe renal insufficiency – creatinine clearance (CK) less than 30 ml/min;

– concomitant administration of clarithromycin with ergot alkaloids, e.g.

ergotamine, dihydroergotamine (see “Interaction with other drugs”).

The concomitant administration of clarithromycin with oral midazolam (see “Interaction with other medicinal products”).

Patients with a history of QT interval prolongation, ventricular arrhythmia, or pirouette-type ventricular tachycardia;

Patients with hypokalemia (risk of QT interval prolongation). – patients with severe hepatic impairment concomitant with renal impairment;

– concomitant administration of clarithromycin with HMG-CoA reductase inhibitors./p>

(statins) that are significantly metabolized by CYP3A4 isoenzyme (lovastatin, simvastatin), due to an increased risk of myopathy, including rhabdomyolysis (see “Interaction with other agents”).

– concomitant administration of clarithromycin with colchicine in patients with impaired hepatic or renal function;

– patients with a history of cholestatic jaundice/hepatitis developed during the use of clarithromycin (see “Cautionary Notes”).

– patients with cholestatic jaundice/hepatitis with a history of clarithromycin (see section “Special Precautions”);

– breastfeeding period;

– children under 12 years of age (effectiveness and safety have not been established);

– porphyria;

– lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Moderate renal insufficiency;

– moderate to severe hepatic insufficiency;

– myasthenia gravis (possible worsening of symptoms);

– concomitant administration of clarithromycin with benzodiazepines, such as alprazolam, triazolam, midazolam for intravenous use (see “Interaction with other medicinal products”). concomitant administration of clarithromycin with benzodiazepines such as alprazolam, triazolam, and midazolam intravenous (see section “Interaction with other drugs”). – 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”)

– concomitant administration with drugs that induce CYP3A4 isoenzyme, e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort (see section “Interaction with other medicinal products”).

– concomitant administration 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, severe bradycardia (less than 50 bpm), as well as patients concomitantly taking antiarrhythmic drugs of class IA (quinidine, procainamide) and class III (dofetilide, amiodarone, sotalol);

– pregnancy.

Side effects

Adverse reactions are presented according to the effect on organs and organ systems.

The 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), unknown (adverse effects from post-marketing experience; frequency cannot be estimated based on available data).

Allergic reactions

Often – rash.

Infrequent – anaphylactoid reaction1, hypersensitivity, bullous dermatitis1, itching, urticaria, maculopapular rash.

Unknown – anaphylactic reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptomatology (DRESS syndrome).

Nervous system disorders

Often – headache, insomnia.

Infrequent – loss of consciousness1, dyskinesia1, dizziness, drowsiness, tremor, restlessness, hyperexcitability, screaming.

Unknown – seizures, psychotic disorders, confusion, depersonalization, depression, disorientation, hallucinations, dream disorders (“nightmares” dreams), paresthesia, mania.

Skin side

Often – intense sweating.

Infrequent – acne, Schoenlein-Henoch purpura, hemorrhages.

In the urinary system

Unknown – renal failure, interstitial nephritis.

Metabolism and nutrition Infrequent – anorexia, decreased appetite.

Unknown – hypoglycemia.

Musculoskeletal system

Infrequent – muscle spasm, musculoskeletal stiffness1, myalgia.

Unknown – rhabdomyolysis*, myopathy, exacerbation of symptoms of myasthenia gravis.

In the digestive system

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

Infrequent – esophagitis1, gastroesophageal reflux disease, gastritis, proctalgia, stomatitis, glossitis, bloating, constipation, dry mouth, belching, flatulence, cholestasis, hepatitis, including cholestatic and hepatocellular.

Unknown – acute pancreatitis, discoloration of tongue and teeth, liver failure, cholestatic jaundice.

In the respiratory system

Infrequent – asthma1, nasal bleeding, pulmonary embolism1.

Sensory organs

Often – dysgeusia, perversion of taste.

Infrequent – vertigo, hearing impairment, tinnitus.

Unknown – deafness, agueusia (loss of taste), parosmia, anosmia.

Cardiovascular system Often – vasodilation.

Infrequent – atrial flutter, prolongation of QT interval on electrocardiogram, atrial fibrillation1, extrasystole1, cardiac arrest1.

Unknown: Ventricular tachycardia, including pirouette type.

Laboratory findings

Often: abnormal liver function test.

Infrequent – increased creatinine1 concentration, increased urea1 concentration, albumin-globulin1 ratio change, leukopenia, neutropenia, eosinophilia, thrombocythemia, increased activity: alanine aminotransferase (ALT),aspartate aminotransferase (ACT), gammaglutamyltransferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH).

Unknown – agranulocytosis, thrombocytopenia, increased international normalized ratio (INR) value, prolongation of prothrombin time, change in urine color, increased blood bilirubin concentration.

General disorders

Infrequent – malaise, hyperthermia, asthenia, chest pain, chills, fatigue.

Infectious and parasitic diseases

Infrequent – cellulitis1, candidiasis, gastroenteritis, secondary infections (including vaginal).

Unknown – pseudomembranous colitis, rye, erythrasma.

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 registered an increase in residual urea nitrogen concentration.

* In some reports of rhabdomyolysis, clarithromycin has been taken together with other drugs known to be associated with rhabdomyolysis (statins, fibrates, colchicine or allopurinol).

1 These adverse reactions have been reported in clinical studies as well as in post-marketing use of clarithromycin in the form of lyophilizate for preparation of solution for infusion.

Overdose

Symptoms

The high dose 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 performed. Hemodialysis and peritoneal dialysis have no significant effect on plasma concentrations of clarithromycin, which is typical for other drugs of macrolide group.

Similarities