Klabaks OD - instructions for use, doses, side effects, contraindications

Excipients: hypromellose, lactose monohydrate, microcrystalline cellulose, povidone, colloidal silicon dioxide, sodium stearyl fumarate, talc, magnesium stearate;

film coating: coloring Opadrai yellow 20N52875 (hypromellose, propylene glycol, vanillin, titanium dioxide, giprolase, talc, dye quinoline yellow 18% -24%);

black ink Opacode S-1-17823 (shellac 45% (20% esterified) in ethanol, iron dye oxide black, n-butanol, propylene glycol, isopropanol *, ammonium hydroxide 28%).

* evaporates in the production process

Description:

Oval, biconvex light-yellow tablets, covered with a film shell, with a black ink inprint "CLNXL"on one side.

Pharmacotherapeutic group:Antibiotic-macrolide

ATX: & nbsp

J.01.F.A.09 Clarithromycin

Pharmacodynamics:Macrolide bacteriostatic second-generation antibiotic from the group of macrolides of a wide spectrum of action. It breaks the synthesis of the protein of microorganisms (binds to the 50S subunit of the ribosome membrane of the microbial cell). Active in relation to: Streptococcus agalactiae (Streptococcus pyogenes, Streptococcus viridans, Streptococcus pneumoniae), Haemophilus influenzae (parainfluenzae), Haemophilus ducreyi, Neisseria gonorrhoeae, Neisseria meningitides, Listeria monocytogenes, Legionella pneumophila, Mycoplasma pneumoniae, Helicobacter (Campylobacter) pylori, Campylobacter jejuni, Chlamydia pneumoniae (trachomatis), Moraxella (Branhamella) catarrhalis, Bordetella pertussis, Propionibacterium acnes, Staphylococcus aureus, Ureaplasma urealyticum, Toxoplasma gondii, 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 the human body is the microbiologically active metabolite of 14-hydroxyclarithromycin. The microbiological activity of the metabolite is the same as that of the starting material, or 1-2 times weaker in respect of most microorganisms. The exception is H.influenzae, in respect of which the efficiency of the metabolite is twice as high. The starting material and its main metabolite exert either an additive or a synergistic effect on H.influenzae in conditions in vitro and in vivo depending on the culture of the bacteria.

Pharmacokinetics:

Clarithromycin is metabolized in the cytochrome P450 3A system (CYP3A) of the liver. Absolute bioavailability is about 50%. With repeated intake of a dose of cumulation is not found, and the nature of metabolism in the human body has not changed.

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

Reception of clarithromycin prolonged action inside at a dose of 500 mg per day allows maintaining equilibrium levels of maximum concentrations of clarithromycin and 14-hydroxyclarithromycin in the blood plasma. The equilibrium maximum concentrations (C_mOh) of clarithromycin and 14-hydroxyclarithromycin in plasma are 1.3 μg / ml and 0.48 μg / ml, respectively. The half-lives of the initial drug and its main metabolite are 5.3 hours and 7.7 hours, respectively. When taking clarithromycin prolonged action inside at a dose of 1000 mg per day (2 tablets of 500 mg), the equilibrium levels of C_max clarithromycin and 14-hydroxyclarithromycin averages 2.4 μg / ml and 0.67 μg / ml, respectively.

The half-lives of the initial drug and its main metabolite are 5.8 hours and 8.9 hours, respectively. The time to reach the maximum concentration (TC_max) when taking doses of 500 mg and 1000 mg per day is about 6 hours. In the equilibrium state, the level of 14-hydroxyclarithromycin does not increase in proportion to the doses of clarithromycin, and the half-lives of clarithromycin and its main metabolite increase with increasing doses.The non-linear character of the pharmacokinetics of clarithromycin is associated with a decrease in the formation of 14-hydroxylated and N-demethylated metabolites when higher doses are used, which indicates the non-linearity of clarithromycin metabolism when taking high doses.

With urine, about 40% of the dose of clarithromycin is released, through the intestine - about 30%%.

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

Dysfunction of the liver

In patients with moderate and severe impairment of the functional state of the liver, but with preserved renal function, there is no need to adjust the dose of clarithromycin. Equilibrium concentration in blood plasma and systemic clearance of clarithromycin does not differ in patients of this group and healthy patients. The equilibrium level of 14-hydroxyclarithromycin concentration in people with impaired liver function is lower than in healthy individuals.

Impaired renal function

If the renal function is impaired, the minimum and maximum content of clarithromycin in the blood plasma increases, the half-life, the area under the concentration-time curve of clarithromycin and the 14-OH metabolite. The elimination constant and excretion in the urine are reduced. The degree of changes in these parameters depends on the degree of impaired renal function.

Elderly patients

In elderly patients, the level of clarithromycin and its 14-OH metabolite in the blood was higher, and excretion was slower than in a group of young people. It is believed that the changes in pharmacokinetics in elderly patients are primarily related to changes in creatinine clearance and the functional state of the kidneys, and not with the age of the patients.

Indications:

Klabaks® OD is indicated for the treatment of infectious diseases caused by sensitive microorganisms. These diseases include:

- infections of the lower respiratory tract (bronchitis, pneumonia);

- infections of the upper respiratory tract (pharyngitis, sinusitis), otitis media;

- infections of the skin and soft tissues (folliculitis, erysipelas);

- common or localized mycobacterial infections caused by Mycobacterium avium and Mycobacterium intracellulare;

- localized infections, caused by Mycobacterium chelonae, Mycobacterium fortuitum and Mycobacterium kansasii;

- Klabaks® OD is shown for liquidation N.pylori and a decrease in the recurrence rate of duodenal ulcers associated with N.pylori.

Contraindications:

- Klabaks® OD is contraindicated in patients with increased sensitivity to antibiotics from the macrolide group;

- when treating clarithromycin, do not prescribe ergot derivatives;

- when treating clarithromycin it is forbidden to take cisapride, pimozide, astemizole and terfenadine (see also section Interaction with other medicinal products). In patients taking these drugs concomitantly with clarithromycin, there is an increase in their concentration in the blood. It is possible to prolong the QT interval and develop cardiac arrhythmias, including ventricular paroxysmal tachycardia, ventricular fibrillation and flutter or ventricular fibrillation.

- severe violations of the liver and / or kidney function (creatinine clearance (CK) less than 30 ml / min);

- porphyria;

- children under 12 years (for this dosage form).

Pregnancy and lactation:

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

Therefore, during pregnancy clarithromycin appoint only if there is no alternative therapy if the intended benefit exceeds the possible risk to the fetus.

Clarithromycin penetrates into the female milk, so if it is necessary to use it during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Adults and children over 12 years of age:

Usually Klabaks® OD tablets of prolonged action are prescribed 500 mg once a day during meals. In severe cases, the dose is increased to 500 mg twice a day.

Tablets Klabaks® OD prolonged action can not be broken, chewed, they must be swallowed whole.

Duration of treatment is 7-14 days.

For patients with KK 30-60 ml / min only in severe infections, a dose of 500 mg once a day (ie, a reduction in the daily dose by 50%) is possible.

Side effects:

The most frequent complaints are from the gastrointestinal tract (nausea, dyspepsia, abdominal pain, vomiting and diarrhea). There are reports of the development of pseudomembranous colitis from the middle severe course to life threatening. Other adverse reactions include headaches, taste disorders and transient increases in liver enzyme activity.

There are reports of rare cases of development of paresthesia, as well as hepatitis with an increase in the level of liver enzymes in the blood, the development of cholestasis and jaundice, which in some cases was severe, but, as a rule, reversible. In exceptional cases, hepatic insufficiency was observed with a fatal outcome.

It is known about rare cases of an increase in the concentration of creatinine in the serum, the development of interstitial nephritis, the development of renal failure.

When taking clarithromycin, allergic reactions were observed, the intensity of which varied from hives and skin rashes to anaphylaxis and Stevens-Johnson syndrome.

There are reports of hearing loss during the treatment with clarithromycin, which in most cases was restored after the drug was discontinued. There may also be changes in the perception of taste, which, as a rule, arise together with a taste disorder.

There are data on the development of glossitis, stomatitis, candidiasis of the oral mucosa and changes in the color of the tongue during the treatment with clarithromycin. It is also reported that in most cases reversible tooth discoloration in patients who received clarithromycin.

In rare cases, hypoglycemia was noted; in a number of these cases, hypoglycemia developed in patients taking hypoglycemic agents for oral intake or insulin during the treatment with clarithromycin.

Individual cases of thrombocytopenia and leukopenia have been reported.

When taking clarithromycin, transient side effects on the central nervous system were observed: dizziness, anxiety, fear, insomnia, nightmares, tinnitus, confusion, disorientation, hallucinations, psychoses and depersonalization.

In the treatment with clarithromycin, as with other macrolides, the lengthening of the interval QT, ventricular arrhythmia, including ventricular paroxysmal tachycardia and flutter or fibrillation of the ventricles.

Overdose:

Probably the development of symptoms from the gastrointestinal tract (nausea, vomiting, diarrhea), headache, confusion.

In case of an overdose, immediate gastric lavage and symptomatic treatment are necessary. Hemodialysis and peritoneal dialysis do not lead to a significant change in the level of clarithromycin in the blood serum.

Interaction:

With simultaneous intake increases the concentration in the blood of drugs metabolized in the liver with the help of 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.

It is reported that there are rare cases of acute necrosis of skeletal muscles that coincide in time with simultaneous administration of clarithromycin and inhibitors of hydroxymethylglutaryl-CoA reductase, lovastatin and simvastatin.

There are reports of an increase in the concentration of digoxin in the plasma of patients receiving concomitantly digoxin and clarithromycin tablets. Such patients need constantly monitor the digoxin content in the serum to avoid digitalis intoxication.

Clarithromycin can reduce the clearance of triazolam and, thus, increase its pharmacological effects with the development of drowsiness and confusion.

The simultaneous use of clarithromycin and ergotamine (ergot derivative) can lead to acute ergotamine intoxication, manifested by severe vasospasm and ischemia of limbs and other tissues.

Simultaneous administration of zidovudine orally to HIV-infected adults and clarithromycin tablets may lead to a decrease in equilibrium concentrations of zidovudine. Given the fact that clarithromycinprobably changes the absorption of the zidovudine administered simultaneously with it, this interaction is largely avoided when taking clarithromycin and zidovudine at different hours of the day (with an interval of at least 4 hours).

With the simultaneous administration of clarithromycin and ritonavir, the serum concentration of clarithromycin increases. Correction of the dose of clarithromycin in these cases in patients with normal renal function is not required. However, in patients with creatinine clearance from 30 to 60 ml / min, the dose of clarithromycin should be reduced by 50%, and with creatinine clearance less than 30 ml / min. Do not administer prolonged-action clarithromycin tablets. Such patients are appointed clarithromycin rapid release of 250 mg or 500 mg. With simultaneous treatment with ritonavir should not be prescribed clarithromycin in doses over 1 g / day.

Special instructions:

In the presence of chronic liver diseases it is necessary to carry out regular monitoring of serum enzymes.

Caution is prescribed against the background of drugs metabolized by the liver (it is recommended to measure their concentration in the blood).

In the case of co-administration with warfarin or other indirect anticoagulants, prothrombin time should be monitored.

It is necessary to pay attention to the possibility of cross-resistance between clarithromycin and other antibiotics from the macrolide group, as well as lincomycin and clindamycin.

With prolonged or repeated use of the drug, it is possible to develop superinfection (re-infection with the same pathogens against the background of the developed disease).

Children under 12 years of age are advised to use Klabaks® OD in a granule dosage form to prepare a suspension for ingestion of 250 mg / 5 ml, 125 mg / 5 ml.

Form release / dosage:

Tablets of prolonged action, film-coated, 500 mg.

Packaging:

For 5 tablets in a blister of aluminum foil PVC / PVDNH; 1 or 2 blisters together with instructions for use in a cardboard bundle

For 7 tablets in a blister of aluminum foil / PVC / PVDNH; 1 or 2 blisters together with instructions for use in a cardboard pack.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-000837/08

Date of registration:18.02.2008 / 04.04.2017

Expiration Date:Unlimited

The owner of the registration certificate:Ranbaxy Laboratories LimitedRanbaxy Laboratories Limited India

Manufacturer: & nbsp

RANBAXY LABORATORIES, Ltd. India

Representation: & nbspRABBAYS LABORATORY LIMITEDRABBAYS LABORATORY LIMITED

Information update date: & nbsp15.03.2011

Illustrated instructions

Instructions

Klabaks® OD (Klabax® OD)