Clarithromycin, 500 mg 14 pcs

Pharmacological action – broad spectrum antibacterial.

Pharmacological action:

Clarithromycin is a broad spectrum semi-synthetic macrolide antibiotic. Antibacterial activity of clarithromycin is carried out by inhibition of protein synthesis due to binding to 50s-subunit of bacterial ribosomes. Clarithromycin has pronounced activity against a wide range of aerobic and anaerobic gram-positive and gram-negative organisms. Minimum inhibitory concentration of clarithromycin (MIC) is half that of erythromycin for most microorganisms.

The 14-hydroxy metabolite of clarithromycin also has antimicrobial activity. Minimum inhibitory concentrations of this metabolite are equal to or greater than the MAC of clarithromycin; against H. influenzae 14-hydroxy metabolite is twice as active as clarithromycin.

Clarithromycin has in vitro activity against the following organisms – Gram-positive aerobic bacteria: Staphylococcus aureus (sensitive to methicillin), 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.

Bactericidal activity of clarithromycin is against some bacterial strains: Haemophilus influenzae; Streptococcus pneumoniae; Streptococcus pyogenes; Streptococcus agalactiae; Moraxella (Branhamella) catarrhalis; Neisseria gonorrhoeae; Helicobacter pylori and Campylobacter spp.

Pharmacokinetics:

Clarithromycin is quickly 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 has no effect on the bioavailability of clarithromycin; however, it slightly slows down the onset of clarithromycin absorption and the formation of the 14-hydroxy metabolite. The pharmacokinetics of clarithromycin are nonlinear, with equilibrium concentration reached 2 days after initiation of the drug.

Clarithromycin is excreted with the urine and also with the feces, mainly through the bile. When taking 250 mg of clarithromycin 2 times per day. 15-20% of the administered dose is excreted unchanged in the urine. When administered 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%.

The plasma concentration of clarithromycin is higher when 500 mg of clarithromycin is taken 3 times/day than when this dose is taken 2 times/day.
Clarithromycin content in tissues, including glandular and pulmonary tissue, is several times higher than in circulating blood. At therapeutic concentrations, clarithromycin is 80% bound to plasma proteins.

Clarithromycin penetrates gastric mucus. Clarithromycin levels in gastric mucus and tissues are increased when combined therapy with omeprazole. Clarithromycin penetrates 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);

Active ingredient

Composition

1 film-coated tablet:

the active ingredient:

clarithromycin 500 mg

excipients: povidone, 20 mg; MCC, 324 mg; croscarmellose sodium, 40 mg; colloidal silicon dioxide, 6 mg; magnesium stearate, 10 mg,

film jacket: Opadry II white (hypromellose – 34.95%, lactose monohydrate – 27.18%, titanium dioxide – 25.24%, macrogol 4000 – 9.7%, sodium citrate dihydrate – 2.93%) – 20 mg.

How to take, the dosage

Orally, regardless of meals.

The usual recommended dose of clarithromycin in adults and children over 12 years of age is 250 mg 2 times daily (in this case the form of Clarithromycin-Teva film-coated tablets, 250 mg, may be used).

Interaction

Concomitant administration of clarithromycin with cisapride, pimozide and terfenadine results in increased plasma concentrations of these drugs, which may cause prolongation of the QT interval and cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation arrhythmia and torsade de pointes; similar effects are observed with simultaneous administration of astemizole and other macrolides.

Clarithromycin does not interact with oral contraceptives.

. As with other macrolide antibiotics, concomitant use of clarithromycin and other drugs metabolized with cytochrome P450 (warfarin, ergot alkaloids, triazolam, midazolam, disopyramide, lovastatin, rifabutin, phenytoin, cyclosporine and tacrolimus) may be associated with increased serum concentrations of the above drugs.

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

Concomitant use of clarithromycin and theophylline increases the serum concentration of theophylline and its toxicity.

The concomitant administration of clarithromycin and warfarin or digoxin may be accompanied by an increase in their effects.

The concomitant administration of clarithromycin and carbamazepine may increase the effects of carbamazepine due to decreased excretion rate of carbamazepine.

Concomitant administration of clarithromycin and zidovudine (oral) in HIV-infected adults may decrease the equilibrium concentration of zidovudine; this can be largely avoided by increasing the interval between doses of clarithromycin and zidovudine to 1-2 hours. No such interaction has been noted in children.

The pharmacokinetic parameters: AUC, Cmax, Cmin are increased for the latter when ritonavir and clarithromycin are taken simultaneously. Dose adjustments are usually not necessary in patients with normal renal function 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 plasma concentrations, but usually no dosage adjustment is required.

Concomitant use of clarithromycin and hypoglycemic agents, including insulin may cause hypoglycemia in rare cases.

Special Instructions

Administration of clarithromycin tablets in children younger than 12 years is not recommended.

The prothrombin time should be monitored regularly when clarithromycin and warfarin are prescribed concomitantly.

When clarithromycin and digoxin are concomitantly prescribed, serum digoxin levels should be monitored.

Contraindications

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

– concomitant use of clarithromycin with the following drugs: astemizole, cisapride, pimozide, terfenadine, ergot alkaloids (e.g., ergotamine, dihydroergotamine), oral midazolam (see “

– concomitant administration of clarithromycin with HMG-CoA reductase inhibitors (statins) that are largely metabolized by the CYP3A4 isoenzyme (lovastatin, simvastatin), due to an increased risk of myopathy, including rhabdomyolysis;

– concomitant use of colchicine in patients with hepatic and/or renal dysfunction;

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

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

p> – severe renal impairment (creatinine clearance less than 30 mL/min), concomitant use of clarithromycin with ticagrelor or ranolazine;

– severe hepatic impairment concomitant with renal impairment;

– cholestatic jaundice/hepatitis with clarithromycin (history);

– porphyria;

– hypokalemia (risk of QT interval prolongation);

– lactation (breastfeeding) period;

– Children under 12 years of age (efficacy and safety not established);

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

With caution

– moderate renal failure;

– moderate to severe hepatic failure;

– CHD, severe heart failure, significant bradycardia (less than 50 bpm);

– concomitant administration of clarithromycin with other ototoxic agents, particularly aminoglycosides;

– concomitant administration of clarithromycin with statins that are independent of CYP3A isoenzyme metabolism (e.g., fluvastatin);

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

– concomitant administration with drugs that are metabolized by the CYP3A4 isoenzyme, such as carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants (eg: warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine;

– Concurrent use with drugs that induce CYP3A4 isoenzyme (e.g: rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort);

– concomitant administration with “slow” calcium channel blockers that are metabolized by CYP3A4 isoenzyme (e.g: verapamil, amlodipine, diltiazem);

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

– hypomagnesemia;

– pregnancy.

Side effects

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

Blood system disorders: in exceptional cases – leukopenia and thrombocytopenia; increase in serum creatinine level.

Central and peripheral nervous system: paresthesia, headache, disorders of smell, change in taste sensation; dizziness, agitation, insomnia, nightmares, fear, tinnitus, confusion, disorientation, hallucinations, psychosis, depersonalization; reversible hearing loss; seizures.

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

Motor system disorders: arthralgia, myalgia.

Treatment of the urinary system: single cases of increased blood plasma creatinine, interstitial nephritis, renal failure.

Allergic reactions: urticaria, angioneurotic edema, anaphylactic shock, in rare cases – Stevens-Johnson syndrome, toxic edermal necrolysis.

Others: rare – hypoglycemia in patients taking oral hypoglycemic drugs or insulin.

Overdose

Symptoms: gastrointestinal symptoms; one patient had a case of mental disturbance, paranoid behavior, hypoglycemia, hypoxemia while taking 8 g of clarithromycin.

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

Similarities