Clarithromycin retard-OBL - instructions for use, dose, side effects, contraindications

Excipients: hydroxypropylmethylcellulose (hypromellose), aerosil (silicon dioxide colloid), kollidone SR [polyvinyl acetate 80%, povidone 19%, sodium lauryl sulfate 0.8%, silicon dioxide 0, 2%], magnesium stearate;

shell composition: giprolose (hydroxypropyl cellulose), macrogol 6000, titanium dioxide, hyetellose (hydroxyethylcellulose), vanillin.

Description:

The tablets covered with a cover of white color, biconcave, oblong form with the rounded ends, with risk. Two layers are visible on the cross-section.

Pharmacotherapeutic group:antibiotic-macrolide

ATX: & nbsp

J.01.F.A.09 Clarithromycin

Pharmacodynamics:

Bacteriostatic antibiotic of the second generation from the group of macrolides of a wide spectrum of action. Disrupts the synthesis of the protein of microorganisms (binds to 50S subunit of the ribosome membrane of a microbial cell). It acts on extracorporeal and intracellular pathogens.

Active in relation to:

Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus viridans, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus ducreyi, Neisseria gonorrhoeae, Neisseria meningitides, Listeria monocytogenes, Legionella pneumophila, Mycoplasma pneumoniae, Helicobacter (Campylobacter) pylori, Campylobacter jejuni, Chlamydia pneumoniae, Moraxella catarrhalis, Bordetella pertussis, Mycobacterium avium, Mycobacterium leprae, Staphylococcus aureus, Mycobacterium kansasii, Mycobacterium marinum, Ureaplasma urealyticum, Toxoplasma gondii, Corynebacterium spp., Borrelia burgdorferi, Pasteurella multocida, some anaerobes (Eubacter spp., Peptococcus spp., Propionibacterium spp., Clostridium perfringens, Bacteroides melaninogenicus).

Pharmacokinetics:

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. Absolute bioavailability is about 50%. 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 preparation and its main metabolite are 5.3 hours and 7.7 hours, respectively. When taking prolonged-action of clarithromycin in a dose of 1000 mg per day (2 tablets of 500 mg), the equilibrium levels of C_mOh clarithromycin and 14-hydroxycl-rithromycin averages - 2.4 μg / ml and 0.67 μg / ml, respectively. The half-lives of the initial preparation and its main metabolite are 5.8 hours and 8.9 hours, respectively. The time to reach the maximum concentration (T_mOh) when taking doses of 500 mg and 1,000 mg per day is about 6 hours.

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.

Clarithromycin is metabolized in the cytochrome P450 3A (CUR3A) system of the liver.

With repeated administration of the drug 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.

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 nature of the pharmacokinetics of clarithromycin is associated with a decrease in the formation of 14-hydroxylated and N-detylated metabolites when higher doses are used, which indicates the non-linearity of clarithromycin metabolism when taking high doses. About 40% of the dose of clarithromycin is secreted by the kidney, about 30% through the intestine.

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

When 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 14-hydroxyclarithromycin. The elimination constant and excretion by the kidneys decrease. 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-hydroxyclarithromycin in the blood was higher, and excretion is slower than in the 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:

Infectious inflammatory diseases caused by microorganisms sensitive to the preparation, including atypical pathogens:

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

- infection of the upper respiratory tract (pharyngitis, sinusitis);

- infections of the skin and soft tissues (such as folliculitis, erysipelas).

Contraindications:

- Hypersensitivity to drugs of the macrolide group;

- severe renal failure - creatinine clearance less than 30 ml / min;

- simultaneous reception of clarithromycin with the following drugs: astemizole, cisapride, pimozide and terfenadine;

- porphyria;

- pregnancy;

- lactation period;

- children and adolescents under 18 years (for this dosage form).

Carefully:

Renal and / or hepatic insufficiency.

Against the background of taking medicines metabolized by the liver (it is recommended to measure their concentration in the blood).

Dosing and Administration:

Inside with food.Tablets should not be chewed or broken, they must be swallowed whole.

Adults-500 mg once a day. In severe infections, the dose is increased to 1,000 mg (2 tablets) once a day. Duration of treatment is 6-14 days.

Side effects:

Co cardiovascular system

Rarely, ventricular arrhythmia, including ventricular tachycardia (with an increase in the interval QT).

Co the sides of the digestive system

Nausea, abdominal pain, vomiting, diarrhea, gastralgia, pancreatitis, glossitis, stomatitis, oral cavity candidiasis, discoloration of the tongue and teeth; rarely - pseudomembranous enterocolitis.

The discoloration of the teeth is reversible and is usually restored by professional cleaning at the dentist. Rarely there were violations of liver function, including an increase in the activity of "hepatic" transaminases, liver and / or cholestatic hepatitis with jaundice or without it. These violations of the liver can be severe, but usually they are reversible. Very few cases of hepatic insufficiency and death were observed, mainly on the background of severe co-morbidities and / or concomitant drug therapy.

Co the central nervous system

Transient headaches, dizziness, anxiety, insomnia, nightmares, ringing in the ears, depersonalization, hallucinations, convulsions, fear, rarely - psychosis, confusion.

Co sensory side

Separate cases of hearing loss. However, when the reception of clarithromycin ceased, hearing was restored. There have also been cases of changes in the sense of smell, usually accompanied by distortion of taste sensations.

Allergic reactions

Urticaria, skin flushing, itching, anaphylactic reactions, Stevens-Johnson syndrome.

Changes in laboratory indicators

Leukopenia, thrombocytopenia, an increase in serum creatinine; rarely - hypoglycemia (with simultaneous use of hypoglycemic drugs).

Other

Development of resistance of microorganisms.

Overdose:

Symptoms: disturbance of the function of the gastrointestinal tract, headache, confusion.

Treatment: gastric lavage, symptomatic therapy. Hemodialysis and peritoneal dialysis does not significantly affect the level of clarithromycin in the serum.

Interaction:

Contraindicated the simultaneous use of clarithromycin with cisapride, pimozide, terfenadine, astemizole, as this leads to an increase in the concentration of these drugs in the blood plasma in 2-3 times, which can cause lengthening of the interval QT, disturbance of the rhythm of the heart, including ventricular tachycardia, ventricular fibrillation.

At simultaneous reception clarithromycin increases the concentration in the blood of drugs metabolized in the liver with the help of cytochrome P450 enzymes: indirect anticoagulants, carbamazepine, theophylline, triazolam, midazolam, cyclosporine, vinblastine, disopyramide, phenytoin, rifabutin, simvastatin, lovastatin, digoxin, alprazolam, valproic acid, cilostazolum, methylprednisolone, omeprazole, quinidine, ergot alkaloids, sildenafil, tacrolimus.

At simultaneous reception of clarithromycin and zidovudine in HIV-infected patients, a decrease in the value of the equilibrium concentration of zidovudine is noted, the reception of these drugs should be divided in time.

With the simultaneous use of ritonavir (200 mg every 8 hours) and clarithromycin (500 mg every 12 hours), the metabolism of clarithromycin slows down (C_mOh clarithromycin increased by 31%, C_min - by 182%, AUC - by 77%). There was a significant delay in the formation of 14-hydroxyclarithromycin. When taking ritonavir, do not simultaneously prescribe clarithromycin in a dose of more than 1 g per day. In this case, in patients without renal dysfunction, there is no need to correct the dose of clarithromycin. This is of great importance in the case of using this combination in patients with impaired renal function: for patients with creatinine clearance from 30 to 60 ml / min, the dose of clarithromycin is reduced by 50% (up to 500 mg once a day).

It is possible to develop cross-resistance between clarithromycin, lincomycin and clindamycin.

Special instructions:

In the presence of chronic liver diseases it is necessary to regularly monitor the content of serum enzymes.

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

Form release / dosage:

Tablets of prolonged action, coated with a coating, 500 mg.

Packaging:

For 5.7 or 10 tablets in a contour mesh package.

For 1 or 2 contour packagings together with the instructions for use are placed in a pack.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-003652/09

Date of registration:15.05.2009

The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Manufacturer: & nbsp

OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Representation: & nbspOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCRussia

Information update date: & nbsp05.08.2011

Illustrated instructions

Instructions

Clarithromycin retard-OBL (Clarithromycin retatd-OBL)