Clarithromycin prolonged pills 500 mg, 14 pcs.

Composition

of 1 tab. :

– clarithromycin 500 mg

Auxiliary substances:

Ingredients: povidone,

microcrystalline cellulose,

croscarmellose sodium,

colloidal silicon dioxide,

magnesium stearate.

Shell composition:

opadray II 31F58914 white (hypromelose, lactose monohydrate, titanium dioxide (E 171), macrogol 4000, sodium citrate).

Pharmacological action

Pharmaceutical Group:

macrolide antibiotic.

Pharmaceutical action:

 Clarithromycin is a semi-synthetic broad-spectrum macrolide antibiotic. The antibacterial effect of clarithromycin is achieved by suppressing protein synthesis due to binding to the 50s subunit of bacterial ribosomes. Clarithromycin has a pronounced activity against a wide range of aerobic and anaerobic gram-positive and gram-negative organisms. The minimum inhibitory concentration of clarithromycin (MPC) is half that of erythromycin for most microorganisms.

The 14-hydroxy metabolite of clarithromycin also has antimicrobial activity. The minimum inhibitory concentrations of this metabolite are equal to or exceed the BMD of clarithromycin; against H. influenzae,14-hydroxymetabolite is twice as active as clarithromycin.

Clarithromncin is active in vitro against the following organisms: gram – positive aerobic bacteria: Staphylococcus aureus (methicillin-sensitive), Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus viridans and Listeria monocytogenes; gram-negative aerobic bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoea, Legionella pneumophila, Bordetella pertussis, Helicobacter pylori, Campylobacter jejuni; mainly intracellular microorganisms: Mycoplasma pneumonia, Ureaplasma urealyticum, Chlamydia trachomatis, Chlamydia pneumonia, Mycobacterium avium, Mycobacterium leprae, M. kansaii, M. chelonae, M. marinum, M. fortitum; anaerobic microorganisms: Bacteroides fragilis, Clostridium perfringens, Propionibacterium acnes, Peptococcus species; Peptostreptococcus species. In addition, the drug is active against Toxoplasma species.

Clarithromycin has bactericidal activity against certain bacterial strains: Haemophilus influenzae; Streptococcus pneumoniae; Streptococcus pyogenes; Streptococcus agalactiae; Moraxella (Branhamella) catarrhalis; Neisseria gonorrhoeae; Helicobacter pylori and Campylobacter spp.

: 

Clarithromycin is rapidly and well absorbed from the gastrointestinal tract after oral administration. The microbiologically active metabolite 14-hydroxyclarithromycin is formed after the first passage through the liver. Food intake does not affect the bioavailability of clarithromycin, however, it slightly slows down the onset of clarithromycin absorption and the formation of 14-hydroxymetabolite. The pharmacokinetics of clarithromycin are non-linear; the equilibrium concentration is reached 2 days after the start of taking the drug.

Clarithromycin is excreted in the urine, as well as in the feces, mainly through bile. When taking 250 mg of clarithromycin 2 times/day,15-20% of the administered dose is excreted unchanged in the urine. When taking 500 mg 2 times/day. urinary excretion is about 36%.14-hydroxyclarithromycin is the main metabolite found in the urine, accounting for about 10-15%.

When taking 500 mg of clarithromycin 3 times/day, the concentration of clarithromycin in plasma is higher than when taking this dose 2 times/day. The content of clarithromycin in tissues, including glandular and lung tissue, is several times higher than in circulating blood. At therapeutic concentrations, clarithromycin binds to plasma proteins by 80%.

Clarithromycin penetrates the gastric mucus. The level of clarithromycin in the mucus and tissues of the stomach increases with combination therapy with omeprazole. Clarithromycin passes into breast milk.

Indications

Infections caused by clarithromycin-sensitive microorganisms:- lower respiratory tract infections (including acute and chronic bronchitis, pneumonia);- upper respiratory tract infections (including sinusitis and pharyngitis);- skin and soft tissue infections;— duodenal ulcer for eradication of Helicobacter pylori (as part of complex therapy with proton pump inhibitors).

Contraindications

– hypersensitivity to clarithromycin and other components of the drug, as well as increased sensitivity to other macrolide antibiotics;

– concomitant use of clarithromycin with the following drugs: astemizole, cisapride, pimozide, terfenadine, ergot alkaloids (eg, ergotamine, dihydroergotamine), midazolam for oral administration (see “Interaction with other medicines”);

– concomitant use of clarithromycin with inhibitors of HMG-COA reductase (statins), which are largely metabolized by CYP3A4 (lovastatin, simvastatin), in connection with the increased risk of myopathy, including rhabdomyolysis;

– concomitant use of colchicine in patients with impaired liver function and/or kidney;

– concomitant use of inhibitors of P-glycoprotein or potent inhibitors of CYP3A4;

– patients with QT prolongation or history of ventricular arrhythmia, including polymorphic ventricular tachycardia (“torsade de pointes”);

– severe renal insufficiency (creatinine clearance less than 30 ml/min), concomitant use of clarithromycin with ticagrelor or ranolazine;

– severe liver failure, occurring simultaneously with renal insufficiency;

– cholestatic jaundice/hepatitis encountered in the application of clarithromycin (in the anamnesis);

– porphyria;

– hypokalaemia (risk of QT interval prolongation);

– lactation period (breastfeeding);

– children’s age up to 12 years (effectiveness and safety not established);

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

Caution

– renal failure of moderate severity;

– liver failure moderate and severe degrees of severity;

– ischemic heart disease, severe heart failure, bradycardia (less than 50 beats/min);

– simultaneous administration of clarithromycin with other ototoxic drugs, especially with aminoglycosides;

– concomitant use of clarithromycin with statins, independent of the isoenzyme CYP3A metabolism (e. g. fluvastatin);

– concomitant use with benzodiazepines, such as alprazolam, triazolam, midazolam for intravenous use;

– simultaneous administration of drugs that are metabolized by CYP3A4, for example, carbamazepine, Cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants (e. g. warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine;

– simultaneous administration of drugs that induce CYP3A4 (e. g. rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort);

– simultaneous reception of blockers “slow” calcium channels, which are metabolized by CYP3A4 (e. g. verapamil, amlodipine, diltiazem);

– concomitant use of antiarrhythmic drugs of class IA (quinidine, procainamide) and class III (dofetilide, amiodarone, sotalol);

– hypomagnesemia;

– pregnancy.

Side effects

Clarithromycin is usually well tolerated by patients

Gastrointestinal disorders: nausea, vomiting, dyspepsia, diarrhea, abdominal pain, stomatitis, glossitis, pancreatitis, oral candidiasis, discoloration of the tongue and teeth; rarely-pseudomembranous enterocolitis. Discoloration of the teeth is reversible and usually restored by special treatment in a dental clinic. As with other macrolide antibiotics, liver function disorders may occur, including increased activity of liver enzymes, hepatic cell and / or cholestatic hepatitis with or without jaundice. These liver function disorders can be severe, but they are usually reversible. Very rare cases of liver failure and death were observed, mainly against the background of severe concomitant diseases and/or concomitant drug therapy.

From the blood system: in exceptional cases-leukopenia and thrombocytopenia; increased serum creatinine.

From the central and peripheral nervous system: paresthesia, headache, olfactory disorders, changes in taste sensations; dizziness, agitation, insomnia, nightmares, fear, ringing in the ears, confusion, disorientation, hallucinations, psychosis, depersonalization; reversible hearing loss; convulsions.

From the cardiovascular system: as with other macrolides, prolongation of the QT interval, ventricular tachycardia, polymorphic ventricular tachyarrhythmia (torsades de pointes).

Musculoskeletal system disorders: arthralgia, myalgia.

From the urinary system: isolated cases of increased plasma creatinine, interstitial nephritis, renal failure.

Allergic reactions: urticaria, angioedema, anaphylactic shock, in rare cases – Stevens-Johnson syndrome, toxic elidermalkiy necrolysis.

Other: rarely-hypoglycemia in patients taking oral hypoglycemic drugs or insulin.

Interaction

When clarithromycin is co-administered with cisapride, pimozide, and terfenadine, elevated plasma concentrations of these drugs are observed, which can cause QT prolongation and cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, arrhythmia, and torsade de pointes; similar effects are observed with concomitant use of astemizole and other macrolides.

Clarithromycin does not interact with oral contraceptives.

As with other macrolide antibiotics, concomitant administration of clarithromycin and other drugs metabolized with the participation of cytochrome P 450 (warfarin, ergot alkaloids, triazolam, midazolam, disopyramide, lovastatin, rifabutin, phenytoin, cyclosporine and tacrolimus) may be accompanied by an increase in the concentration of these drugs in the blood serum.

Concomitant use of clarithromycin and HMG-KoA reductase inhibitors (lovastatin, simvastatin) may cause rhabdomyolysis.

Concomitant administration of clarithromycin and theophylline increases the concentration of theophylline in the blood serum and its toxicity.

Concomitant administration of clarithromycin and warfarin or digoxin may be accompanied by an increase in the severity of their effects.

Concomitant administration of clarithromycin and carbamazepine may increase the effect of carbamazepine due to a decrease in the rate of carbamazepine excretion.

Concomitant administration of clarithromycin and zidovudine (orally) in HIV-infected adult patients may reduce the steady-state concentration of zidovudine; this can be largely avoided by increasing the interval between clarithromycin and zidovudine doses to 1-2 hours. No such interaction was observed for children.

With simultaneous administration of ritonavir and clarithromycin, the values of pharmacokinetic parameters for the latter increase: AUC, Cmax, Cmin. For patients with normal renal function, dose adjustment is usually not required due to the wide therapeutic dose range of clarithromycin.

Concomitant use of clarithromycin and omeprazole, clarithromycin and lansoprazole, as well as clarithromycin and ranitidine may increase the concentration of drugs in the blood plasma, but usually no dose adjustment is required.

With the simultaneous use of clarithromycin and hypoglycemic agents, including insulin, hypoglycemia may develop in rare cases.

How to take, course of administration and dosage

Tablets should be taken orally with meals. Tablets should not be broken or chewed, they must be swallowed whole.

Adults and children over 12 years of age – 1 tablet (500 mg) 1 time a day with meals. In severe cases, the dose is increased to 2 tablets (1000 mg) once a day with meals. The duration of treatment is usually 5-14 days. The exceptions are community-acquired pneumonia and sinusitis, which require treatment for 6 to 14 days.

Overdose

Symptoms: symptoms from the gastrointestinal tract; one of the patients taking 8 g of clarithromycin had a case of mental disorders, paranoid behavior, hypoglycemia, hypoxemia.

Treatment: gastric lavage, maintenance therapy. Hemodialysis or peritoneal dialysis is ineffective, as with other macrolides.

Special instructions

Taking clarithromycin tablets in children under 12 years of age is not recommended.

When clarithromycin and warfarin are co-administered, prothrombin time should be monitored regularly.

When clarithromycin and digoxin are administered concomitantly, the level of digoxin concentration in the blood serum should be monitored.

Form of production

Long-acting film-coated tablets

Storage conditions

At a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date indicated on the package.

Active ingredient

Clarithromycin

Conditions of release from pharmacies

By prescription

Dosage form

of long-acting tablets

Indications

Bronchitis, Sinusitis, Pharyngitis, Skin Infections, Pneumonia, Otitis Media, Gastrointestinal Infections, Chlamydia

Weight

Weight: 300 gr.