Clabax OD, prolong. 500 mg 7 pcs.

Pharmacological action – antibacterial.

Pharmacodynamics

A second generation bacteriostatic macrolide antibiotic from the group of broad-spectrum macrolides. It disrupts protein synthesis of microorganisms (binds with 50S subunit of the ribosome membrane of the microbial cell).

It is active against: Streptococcus agalactiae (Streptococcus pyogenes, Streptococcus viridans, Streptococcus pneumoniae), Haemophilus influenzae (parainfluenzae), Haemophilus ducreyi, Neisseria gonorrhoeae, Neisseria meningitidis, Listeria monocytogenes, Legionella pneumophila, Mycoplasma pneumoniae, Helicobacter (Campylobacter) pylori, Campylobacter jejuni, Chlamidia pneumoniae (trachomatis), Moraxella (Branhamella) catarrhalis, Bordetella pertussis, Propionibacterium acnes, Staphylococcus aureus, Ureaplasma urealyticum, Toxoplasma gondii, Corynebacterium spp., Borrelia burgdorferi, Treponema pallidum, Pasteurella multocida, some anaerobes (Eubacterium spp., Peptococcus spp., Propionibacterium spp., Clostridium perfringens, Bacteroides melaninogenicus) and all mycobacteria except M. tuberculosis.

The main metabolite of clarithromycin in humans is the microbiologically active metabolite 14-hydroxyclarithromycin. The microbiological activity of the metabolite is the same as that of the parent substance, or 1-2 times weaker against most microorganisms. The exception is H.influenzae, against which the effectiveness of the metabolite is 2 times higher. The starting substance and its main metabolite have either additive or synergistic effect against H.influenzae under in vitro and in vivo conditions depending on the bacterial culture.

Pharmacokinetics

Clarithromycin is metabolized in the liver cytochrome P4503A (CYP3A) system. Absolute bioavailability is about 50%. No cumulation was found when taking the drug multiple times and the character of metabolism in human body does not change.

Clarithromycin binds to plasma proteins by 70% at concentrations from 0.45 to 4.5 µg/ml. At a concentration of 45 µg/ml, the binding decreases to 41%, probably as a result of saturation of the binding sites. This is observed only at concentrations many times greater than the therapeutic concentration.

The oral administration of prolonged-acting clarithromycin at a dose of 500 mg daily maintains equilibrium levels of maximum plasma concentrations of clarithromycin and 14-hydroxyclarithromycin. The equilibrium Cmax of clarithromycin and 14-hydroxyclarithromycin in plasma are 1.3 and 0.48 µg/ml, respectively. T1/2 of the starting drug and its main metabolite are 5.3 and 7.7 h, respectively. When taking clarithromycin prolonged action orally at a dose of 1000 mg per day (2 tablets of 500 mg) equilibrium levels of Cmax of clarithromycin and 14-hydroxyclarithromycin are on average 2.4 and 0.67 µg/ml, respectively. The T1/2 of the parent drug and its major metabolite are 5.8 and 8.9 h, respectively. The Tmax value when taking doses of 500 and 1000 mg per day is about 6 h. At equilibrium, 14-hydroxyclarithromycin levels do not increase in proportion to clarithromycin doses, and the T1/2 of clarithromycin and its main metabolite increase with increasing dose. The nonlinear nature of clarithromycin pharmacokinetics is associated with a decrease in the formation of 14-hydroxylated and N-demethylated metabolites at higher doses, indicating that clarithromycin metabolism is nonlinear at high doses.

The urine excretes about 40% of the clarithromycin dose and the intestine excretes about 30%.

Clarithromycin and 14-hydroxyclarithromycin are widely distributed in tissues and body fluids. After oral administration of clarithromycin, its content in cerebrospinal fluid remains low (with normal HEB permeability, 1-2% of serum levels). Its content in tissues is usually several times higher than in blood serum.

Disorders of liver function. No adjustment of clarithromycin dose is required in patients with moderate to severe hepatic dysfunction but preserved renal function. Equilibrium plasma concentration and systemic clearance of clarithromycin do not differ between patients in this group and healthy patients. Equilibrium concentrations of 14-hydroxyclarithromycin are lower in people with liver dysfunction than in healthy subjects.

Kidney dysfunction. Impaired renal function increases minimum and maximum plasma levels of clarithromycin, T1/2, AUC of clarithromycin and 14-hydroxyclarithromycin. The elimination constant and urinary excretion decreases. The degree of change in these parameters depends on the degree of renal impairment.

Patients in the elderly. Elderly patients had higher blood levels of clarithromycin and 14-hydroxyclarithromycin and slower excretion than the younger group. Changes in pharmacokinetics in elderly patients are thought to be primarily related to changes in creatinine clearance and renal functional status, rather than to patient age.

Indications

Active ingredient

Composition

clarithromycin 500 mg

accompanied substances:

Hypromelose; lactose monohydrate;

MCC;

povidone;

silicon dioxide colloid;

sodium stearyl fumarate;

talc;

magnesium stearate

film coating:

Opadry Yellow dye 20H52875 (hypromellose, propylene glycol, vanillin, titanium dioxide, hyprolose, talc, quinoline yellow dye 18-24%)
ink composition: Opacode-S-1-17734 black ink (shellac 45% (20% esterified) in SD-45 alcohol, black iron oxide dye, n-butanol, propylene glycol, methanol, isopropanol*, ammonium hydroxide 28%)
* evaporated during production

How to take, the dosage

Orally, with meals, without breaking, chewing, swallowed whole.

Adults and children over 12 years of age – usually 500 mg once a day. In severe cases the dose is increased to 500 mg 2 times a day.

The duration of treatment is 7-14 days.

For patients with Cl creatinine 30-60 ml/min only in severe infections, a dose of 500 mg once daily (i.e., a 50% reduction in the daily dose) may be prescribed.

Interaction

Concomitant administration increases blood concentrations of drugs metabolized in the liver by cytochrome P450 enzymes – indirect anticoagulants, carbamazepine, theophylline, astemizole, cisapride, terfenadine (2-3 times), triazolam, midazolam, cyclosporine, disopyramide, phenytoin, rifabutin, lovastatin, digoxin, ergot alkaloids and others.

Rare cases of acute skeletal muscle necrosis have been reported to coincide with concomitant administration of clarithromycin and the hydroxymethylglutaryl-CoA reductase inhibitors lovastatin and simvastatin.

There have been reports of increased plasma concentrations of digoxin in patients receiving concomitant digoxin and clarithromycin tablets. Serum digoxin levels in these patients should be monitored continuously to avoid digitalis intoxication.

Clarithromycin may decrease clearance of triazolam and thus increase its pharmacological effects with development of somnolence and confusion.

The concomitant use of clarithromycin and ergotamine (ergot derivatives) may lead to acute ergotamine intoxication manifested by severe peripheral vasospasm.

The simultaneous administration of oral zidovudine and clarithromycin tablets to HIV-infected adults may decrease equilibrium concentrations of zidovudine. Given that clarithromycin probably alters absorption of zidovudine administered simultaneously, this interaction is largely avoided when clarithromycin and zidovudine are taken at different hours of the day (at least 4 hours apart).

The concomitant administration of clarithromycin and ritonavir increases serum concentrations of clarithromycin. No clarithromycin dose adjustment is required in these cases in patients with normal renal function. However, in patients with creatinine Cl between 30 and 60 ml/min the dose of clarithromycin should be reduced by 50% and in patients with creatinine Cl less than 30 ml/min the sustained release clarithromycin tablets should not be prescribed. Such patients are prescribed rapid-release clarithromycin 250 or 500 mg. Clarithromycin in doses greater than 1 g/day should not be administered concomitantly with ritonavir.

Special Instructions

In the presence of chronic liver disease, regular monitoring of serum enzymes is necessary.

With caution, use with drugs that are metabolized by the liver (it is recommended to measure their blood concentrations).

If coadministration with warfarin or other indirect anticoagulants, PV should be monitored.

Possible cross-resistance between clarithromycin and other antibiotics from the macrolide group and lincomycin and clindamycin should be considered.

In prolonged or repeated use of the drug, superinfection (reinfection with the same pathogens against the background of a developed disease) is possible.

In children under 12 years of age it is recommended to use Clabax® in the form of granules for oral suspension of 125 or 250 mg/5 ml.

Contraindications

Side effects

The most common complaints are gastrointestinal complaints (nausea, dyspepsia, abdominal pain, vomiting, and diarrhea). There are reports of pseudomembranous colitis ranging from moderate to life-threatening. Other adverse reactions include headaches, taste disorders and transient increases in liver enzyme activity.

There have been reports of rare cases of paresthesias as well as hepatitis with elevated liver enzymes in the blood and the development of cholestasis and jaundice, which in some cases have been severe but usually reversible. In exceptional cases, liver failure with lethal outcome was observed.

Rare cases of increased serum creatinine concentration, development of interstitial nephritis, development of renal failure are known.

When taking clarithromycin allergic reactions have been observed, with intensity varying from urticaria and skin rash to anaphylaxis and Stevens-Johnson syndrome.

There have been reports of hearing loss during treatment with clarithromycin, which in most cases recovered after discontinuation of the drug. Impairment of taste is possible.

There are reports of glossitis, stomatitis, oral candidiasis, and discoloration of the tongue during treatment with clarithromycin. There have also been reports of reversible discoloration of teeth in most cases in patients treated with clarithromycin.

Hypoglycemia has been reported rarely; in some of these cases hypoglycemia has occurred in patients who were taking oral hypoglycemic agents or insulin during treatment with clarithromycin.

Overdose

Symptoms: Gastrointestinal symptoms (nausea, vomiting, diarrhea); headache, confusion.

Treatment: immediate gastric lavage and symptomatic treatment. Hemodialysis and peritoneal dialysis do not significantly alter serum clarithromycin levels.

Pregnancy use

The safety of clarithromycin during pregnancy and lactation has not been established. Therefore, clarithromycin is prescribed during pregnancy only if there is no alternative therapy, if the expected benefits exceed the possible risk to the fetus.

Similarities