Clarithromycin pills 250mg №10

Clarithromycin

Clinico-pharmacological group

Macrolide antibiotic group

Mechanism of action

Clarithromycin is a semisynthetic macrolide broad-spectrum antibiotic. The antibacterial effect of Clarithromycin is accomplished by suppressing protein synthesis due to the binding of bacterial ribosomes to the 50s subunit. 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 (BMD) 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 MPK of clarithromycin; in relation to H. influenzae, 14-hydroxymetabolite is twice as active as clarithromycin.

Clarithromncin shows in vitro activity 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; predominantly 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 the Toxoplasma species..

Bactericidal activity of clarithromycin has 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 rapidly and well absorbed from the gastrointestinal tract after oral administration. The microbiologically active metabolite 14-hydroxylarithromycin is formed after the first passage through the liver. Meal does not affect the bioavailability of clarithromycin, however, somewhat slows the beginning of the absorption of clarithromycin and the formation of 14-hydroxymetabolite. The pharmacokinetics of clarithromycin are non-linear; however, the equilibrium concentration is achieved 2 days after the start of the drug.

Clarithromycin is excreted in the urine, as well as in feces, mainly through bile. When receiving 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-hydroxylarithromycin is the major metabolite found in urine, accounting for about 10-15%.

When receiving 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 is 80% bound to plasma proteins.

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 for use of the drug

Infections caused by microorganisms sensitive to clarithromycin:

- lower respiratory tract infections (including acute and chronic bronchitis, pneumonia);

- upper respiratory tract infections (including sinusitis and pharyngitis);

- infections of the skin and soft tissues;

- duodenal ulcer for the eradication of Helicobacter pylori (in combination therapy with proton pump inhibitors).

Dosage and administration

Inside Adults: usual dose is 250 mg 2 times / day for 7 days, if necessary, the dose may be increased to 500 mg 2 times / day for a period of up to 14 days for severe infections.

Children over 12 years old: dosing regimen as for adults.

For the treatment of duodenal ulcers caused by N. pylori (for adults):

Triple therapy regimen (1-14 days): clarithromycin 500 mg 2 times / day; lansoprazole 30 mg 2 times / day; Amoxicillin 1000 mg 2 times / day.

Triple therapy regimen (7 days): clarithromycin 500 mg 2 times / day; lansoprazole 30 mg 2 times / day; Metronidazole 400 mg 2 times / day.

Triple therapy regimen (7 days): clarigromycin 500 mg 2 times / day; Omeprazole 40 mg / day; Amoxicillin 1000 mg 2 times / day or metronidazole 400 mg 2 times / day.

Triple therapy regimen (10 days): Clarithromycin 500 mg 2 times / day is prescribed with amoxicillin 100 mg 2 times / day and omeprazole 20 mg / day.

Dual therapy regimen (14 days): clarithromycin 500 mg 3 times / day, omeprazol orally 40 mg 1 time / day.

At renal impairment usually dose adjustment is not required, except for patients with severe kidney damage (CC <30 ml / min), but if necessary, the total daily dose should be reduced by half, i.e. 250 mg 1 time / day or 250 mg 2 times / day for more severe infections.

While taking ritonavir for patients with impaired renal function recommended dose adjustment according to the following scheme: for patients with CC 30-60 ml / min, the dose of clarithromycin should be reduced by 50%. For patients with QA less than 30 ml / min, the dose of clarithromycin should be reduced by 75%. When combined use of clarithromycin and ritonavir, do not use doses of clarithromycin over 1 g / day.

Side effect

Clarithromycin is usually well tolerated by patients.

From the digestive tract: nausea, vomiting, dyspepsia, diarrhea, abdominal pain, stomatitis, glossitis, pancreatitis, oral candidiasis, discoloration of the tongue and teeth; rarely - pseudomembranous enterocolitis. Tooth discoloration is reversible and is usually restored with a special treatment in a dental clinic. As with the admission of other antibiotics from the group of macrolides, liver dysfunction is possible, including increased liver enzymes, hepatocellular and / or cholestatic hepatitis with or without jaundice. These abnormal liver functions can be severe, but usually they are reversible. Very rarely, there have been cases of liver failure and death mainly due to severe concomitant diseases and / or concomitant drug therapy.

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

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

Cardiovascular: lengthening of the QT interval, ventricular tachycardia, polymorphic ventricular tachyarrhythmia (torsades de pointes) as well as when taking other macrolides.

Musculoskeletal system: arthralgia, myalgia.

Urogenital: isolated cases of increased plasma creatinine, interstitial nephritis, renal failure.

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

Other: rarely, hypoglycemia in patients taking oral hypoglycemic agents or insulin.

Contraindications to the use of the drug

- simultaneous appointment with derivatives of ergot;

- co-administration of the following drugs: cisapride, pimozide, terfenadine;

- children's age up to 12 years;

- pregnancy and lactation.

- hypersensitivity to macrolide antibiotics.

WITH caution: patients with impaired liver and kidney function.

Use of the drug during pregnancy and lactation

The safety of clarithromycin during pregnancy and lactation has not been studied.

The drug penetrates into breast milk. If necessary, use during lactation should stop breastfeeding.

Application for violations of the liver

WITH caution: patients with impaired liver function.

Application for violations of kidney function

At renal impairment usually dose adjustment is not required, except for patients with severe kidney damage (CC <30 ml / min), but if necessary, the total daily dose should be reduced by half, i.e. 250 mg 1 time / day or 250 mg 2 times / day for more severe infections.

special instructions

Taking clarithromycin tablets in children younger than 12 years old is not recommended.

With the simultaneous appointment of clarithromycin and Warfarin, prothrombin time should be regularly monitored.

With the simultaneous appointment of clarithromycin and Digoxin should be monitored for the level of concentration of digoxin in serum.

Overdose

Symptoms: symptoms of the gastrointestinal tract; In one of the patients taking 8 g of clarithromycin, there was a case of mental disorder, paranoid behavior, hypoglycemia, hypoxemia.

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

Drug interaction

With simultaneous administration of clarithromycin with cisapride, pimozide and terfenadine, elevated concentrations of these drugs are observed in the blood plasma, which can cause prolongation of the QT interval and heart rhythm disturbances, including ventricular tachycardia, ventricular fibrillation, arrhythmia and torsade de pointes; similar effects are observed while taking astemizole and other macrolides.

Clarithromycin does not interact with oral contraceptives.

As with other macrolide antibiotics, simultaneous administration of clarithromycin and other drugs that are metabolized with the participation of cytochrome P450 (warfarin, ergot alkaloids, triazolam, midazolam, disopyramide, lovastatin, rifabutin, cyclosporin, cyclosporin, cyclosporin, cyclophorin alkaloids, disopyramide, lovastatin, rifabutin, cyclosporin alkaloids, triazolam, disazyramid, lovastatin, rifabutin, cyclosporin, alkaloids blood.

With the simultaneous use of clarithromycin and HMG-KoA reductase inhibitors (lovastatin, simvastatin), the development of rhabdomyolysis is possible.

With the simultaneous appointment of clarithromycin and theophylline, serum concentration of theophylline and its toxicity increase.

The simultaneous appointment of clarithromycin and warfarin or digoxin may be accompanied by an increase in the severity of their effects.

With the simultaneous appointment of clarithromycin and Carbamazepine, the effect of carbamazepine may increase due to a decrease in the rate of excretion of carbamazepine.

With simultaneous administration of clarithromycin and zidovudine (orally) in HIV-infected adult patients, a decrease in the equilibrium concentration of zidovudine is possible; this can be largely avoided increasing the interval between doses of clarithromycin and zidovudine to 1-2 hours. For children, this interaction was not observed.

At the same time taking ritonavir and clarithromycin for the latter increases the values ​​of pharmacokinetic parameters: AUC, C_max, C_min. For patients with normal renal function, dose adjustment is usually not required due to the wide therapeutic dose range of clarithromycin.

With simultaneous use of clarithromycin and omeprazole, clarithromycin and lansoprazole, as well as clarithromycin and Ranitidine, an increase in the concentration of drugs in the blood plasma is possible, but usually dose adjustment is not required.

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

Pharmacy sales terms

The drug is available on prescription.

Terms and conditions of storage

Store at a temperature not exceeding 25 ° C, out of the reach of children.