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

Excipients: cellulose microcrystalline 33.0 mg, potato starch 15.0 mg, povidone (polyvinylpyrrolidone) 12.0 mg, sodium carboxymethyl starch 7.0 mg, magnesium stearate 3.0 mg;

auxiliary substances (shell): hypromellose 5.4 mg, macrogol 4000 1.6 mg, titanium dioxide 3.0 mg.

Description:

Tablets biconcave form without risks, covered with a film shell of white or almost white color. The presence of a slight surface roughness is allowed.

Pharmacotherapeutic group:Antibiotic-macrolide

ATX: & nbsp

J.01.F.A.09 Clarithromycin

Pharmacodynamics:

Clarithromycin is a semisynthetic antibiotic of the macrolide group and has an antibacterial effect, interacting with 50S ribosomal subunit of sensitive bacteria and suppressing protein synthesis.

Shown, that clarithromycin has antibacterial action against the following pathogens:

- aerobic Gram-positive microorganisms: Staphylococcus aureus, Streptococcus pneumonia, Streptococcus pyogenes, Listeria monocytogenes;

- aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Branhamella (Moraxella) catarrhalis, Neisseria gonorrhoeae, Legionella pneumophila;

- dOther microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae;

- mycobacteria: Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium avium complex (MAC): Mycobacterium avium, Mycobacterium intracellulare.

The production of beta-lactamase does not affect the activity of clarithromycin. Most strains of staphylococcus aureus resistant to methicillin and oxacillin are resistant to clarithromycin.

Clarithromycin exerts its action in vitro and for most strains of the following microorganisms:

- aerobic Gram-positive microorganisms: Streptococcus agalactiae, Streptococci (groups C, F, G), Viridans group streptococci;

- aerobic gram-negative microorganisms: Bordetella pertussis, Pasteurella multocida;

- anaerobic Gram-positive microorganisms: Clostridium perfringens, Peptococcus niger,

Propionibacterium acnes;

- anaerobic gram-negative microorganisms: Bacteroides melaninogenicus;

- Spirochetes: Borrelia burgdorferi, Treponema pallidum; Campylobacter jejuni, Helicobacter pylori.

Pharmacokinetics:

Quickly absorbed from the gastrointestinal tract after oral administration. 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. The intake of food immediately before taking the drug increased the bioavailability of the drug by an average of 25%. Clarithromycin can be applied before meals or during meals. The connection with plasma proteins is more than 90%. After a single dose, 2 peaks of maximum concentration are recorded. The second peak is due to the ability of the drug to concentrate in the gallbladder, followed by a gradual or rapid intake into the intestine and absorption. Time to reach the maximum concentration with oral intake of 250 mg - 1-3 hours.

After oral administration, 20% of the dose is rapidly hydroxylated in the liver by cytochrome enzymes CYP3A4, CYP3A5, CYP3A7 with the formation of the main metabolite - 14-hydroxyclarithromycin, which has a pronounced antimicrobial activity against Haemophilus influenzae. With a regular intake of 250 mg / day, the concentration of unchanged drug and its main metabolite is 1 and 0.6 μg / ml, respectively; the elimination half-life is 3-4 and 5-6 hours, respectively. When the dose is increased to 500 mg / day, the concentration of unchanged drug and its metabolite in plasma is 2.7-2.9 and 0.83-0.88 μg / ml, respectively; the half-life is 4.8-5 and 6.9-8.7 hours, respectively. In therapeutic concentrations, it accumulates in the lungs, skin and soft tissues (concentrations 10 times higher than serum levels).

It is excreted by the kidneys and through the gastrointestinal tract (GIT) (20-30% - in unchanged form, the rest - in the form of metabolites). With a single admission of 250 and 1200 mg kidneys are allocated 37.9 and 46%, through the gastrointestinal tract - 40.2 and 29.1%, respectively.

Indications:

- Infectious-inflammatory diseases caused by microorganisms sensitive to the preparation;

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

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

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

- odontogenic infections;

- mycobacterial infections caused by Mycobacterium avium, Mycobacterium intracellulare;

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

- prevention of the spread of infection caused by the complex Mycobacterium avium (MAC), HIV-infected patients with lymphocyte content Cd 4 (T-helper lymphocytes) not more than 100 in 1 mm³;

- for eradication Helicobacter pylori and a decrease in the frequency of relapses of peptic ulcer duodenum.

Contraindications:

- Hypersensitivity to clarithromycin or other components of the drug;

- the first trimester of pregnancy;

- lactation period;

- porphyria;

- simultaneous reception of clarithromycin with the following drugs: astemizole, cisapride, pimozide, terfenadine, ergotamine, dihydroergotamine (see "Interaction with other drugs");

- children under 12 years of age or at a body weight of less than 40 kg (for this dosage form).

Carefully:

With caution appoint to patients with impaired liver and kidney function.

Pregnancy and lactation:

Clarithromycin is contraindicated in the first trimester of pregnancy. In the second and third trimester of pregnancy, the drug is prescribed only if there is clear evidence if the intended benefit to the mother exceeds the potential risk to the fetus.

If necessary, the appointment in the lactation period should resolve the issue of stopping breastfeeding.

Dosing and Administration:

Inside, regardless of food intake.

Adults and children over 12 years of age (with a body weight of more than 40 kg): the standard dose is 250 mg 2 times a day, with an interval of 12 hours. With sinusitis, severe infections, including those caused by Haemophilus influenzae the dose can be increased to 500 mg twice a day, with an interval of 12 hours.

The average duration of treatment is 7-14 days.

For patients with hepatic insufficiency the recommended dose is 250 mg every 24 hours.

For patients with renal insufficiency (creatinine clearance less than 30 ml / min), the recommended dose is 250 mg every 24 hours or, for more severe infections, 250 mg twice a day, with an interval of 12 hours.

With mycobacterial infections prescribe 500 mg of the drug 2 times a day, with an interval of 12 hours.

With common infections caused by MAC, in AIDS patients:

The recommended dose of clarithromycin for adults and children over 12 years of age (with a body weight of more than 40 kg) is 500 mg twice a day, with an interval of 12 hours.

Treatment should continue as long as there are clinical and microbiological evidence of its usefulness. Clarithromycin should be administered in combination with other antimicrobials.

For the prevention of infections caused by MAC:

The recommended dose of clarithromycin for adults and children over 12 years of age (with a body weight of more than 40 kg) is 500 mg twice a day, with an interval of 12 hours.

With odontogenic infections The dose of clarithromycin is 250 mg twice a day for 5 days.

For eradication of H. pylori

Combination treatment with three drugs

Clarithromycin, 500 mg twice a day, in combination with lansoprazole, 30 mg twice a day, and amoxicillin, 1000 mg twice a day, for 10 days.

Clarithromycin, 500 mg twice a day, in combination with amoxicillin, 1000 mg twice a day, and omeprazole, 20 mg / day, for 7-10 days.

Combination treatment with two drugs

Clarithromycin, 500 mg 3 times a day, in combination with omeprazole at a dose of 40 mg / day, for 14 days, with the appointment within the next 14 days of omeprazole at a dose of 20-40 mg / day.

Clarithromycin, 500 mg 3 times daily, in combination with lansoprazole at a dose of 60 mg / day, for 14 days. To fully heal the ulcer, an additional decrease in the acidity of the gastric juice may be required.

Side effects:

From the side digestive system: decreased appetite, nausea, vomiting, diarrhea, abdominal pain, stomatitis, glossitis, pancreatitis, discoloration of the tongue and teeth; extremely rarely - pseudomembranous enterocolitis. The discoloration of the teeth is reversible and is usually restored by a special treatment in the dental clinic. As with the administration of other antibiotics from the macrolide group, liver function abnormalities are possible, including an increase in hepatic enzyme activity, hepatic cell and / or cholestatic hepatitis with or without jaundice.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.

From the side nervous system: dizziness, headache, paresthesia, smell disorders, changes in taste, excitement, insomnia, nightmares, feelings of fear, ringing in the ears; rarely - disorientation, hallucinations, psychosis, depersonalization, confusion.

From the side of cardio-vascular system: as with the reception of other macrolides, the lengthening of the interval QT, ventricular tachycardia; polymorphic ventricular tachyarrhythmia (torsade de pointe).

From the side hemopoiesis and hemostasis system: rarely - leukopenia and thrombocytopenia (unusual bleeding, hemorrhage).

From the side musculoskeletal system: arthralgia, myalgia.

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

Allergic reactions: hyperemia of the skin, urticaria, skin rash, angioedema, bronchospasm, eosinophilia; rarely anaphylactic shock, Stevens-Johnson syndrome.

Other: an increase in body temperature, possibly the development of superinfection, candidiasis, development of resistance of microorganisms.

Overdose:

Symptoms: symptoms from the gastrointestinal tract; in one patient with a history of bipolar disorder, after receiving 8 g of clarithromycin, disorders of mental state, paranoid behavior, hypoglycemia, hypoxemia were described.

Treatment: gastric lavage, symptomatic therapy.

There is no specific antidote.

Interaction:

Clarithromycin is not prescribed concurrently with cisapride, pimozide, terfenadine. Simultaneous reception of clarithromycin with drugs metabolized with the participation of cytochrome P450 can lead to an increase in the concentration of such drugs in the blood plasma as: triazolam, astemizole, carbamazepine, cilostazol, cisapride, ciclosporin, disopyramide, ergot alkaloids, lovastatin, methylprednisolone, midazolam, omeprazole, oral anticoagulants (for example, warfarin), pimozide, quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, terfenadine, triazolam, vinblastine, phenytoin, theophylline and valproic acid.

With the simultaneous use of clarithromycin with cisapride, an increase in the concentration of cisapride was observed. This can cause an increase in the interval QT, arrhythmia, ventricular tachycardia, fibrillation and fluttering-fibrillation of the ventricles. Similar effects were observed in patients taking clarithromycin simultaneously with pimozide.

Preparations of the group of macrolides affect the metabolism of terfenadine. The level of terfenadine in the blood increases, which can be accompanied by the development of arrhythmia, an increase in the interval QT, ventricular tachycardia, fibrillation and fluttering-fibrillation of the ventricles. The content of acid metabolites of terfenadine increases by 2-3 times, the interval QT increases, however, this does not cause any clinical manifestations. The same picture was observed with simultaneous administration of astemizole with drugs of the macrolide group.

There are reports of the development of flutter-fibrillation of the ventricles with the simultaneous use of clarithromycin and quinidine, and disopyramide.With the simultaneous administration of these drugs, monitoring of their concentration in the blood is required. With the simultaneous use of clarithromycin with digoxin, an increase in serum digoxin was observed. In such patients, it is necessary to monitor the serum digoxin content.

With the simultaneous use of theophylline and carbamazepine with clarithromycin, a moderate but significant (p <0.05) increase in the content of theophylline and carbamazepine in the blood plasma was noted.

With simultaneous administration of clarithromycin with inhibitors of hydroxymethylglutaryl-CoA (HMG-CoA) reductase (for example lovastatin and simvastatin), rare cases of rhabdomyolysis have been described.

Colchicine is a substrate for CYP3A and P-glycoprotein. Clarithromycin and other macrolides are inhibitors CYP3A and P-glycoprotein. With the co-administration of colchicine and clarithromycin, the inhibition of 3-glycoprotein and / or CYP3A can lead to an increase in the action of colchicine. Patients should be closely monitored to identify symptoms of colchicine's toxic effects.

With simultaneous oral administration of clarithromycin and zidovudine in HIV-infected patients, the equilibrium concentration of zidovudine decreased. Because the clarithromycin affects the absorption of zidovudine, taking these two drugs should be separated in time.

Ritonavir significantly slows the metabolism of clarithromycin when taken concomitantly. In this case, the C max value of clarithromycin is increased by 31%, the minimum concentration (Cmin) - by 182%, the area under the curve "concentration-time" - by 77%. There is a significant slowdown in the formation of 14-hydroxyclarithromycin. In this case, in patients without impaired renal function, there is no need to adjust the dose of clarithromycin. When taking ritonavir should not simultaneously prescribe a dosage of clarithromycin more than 1 g per day.

It is possible to develop cross-resistance between clarithromycin and other drugs of the macrolide group, such as lincomycin and clindamycin.

With the simultaneous use of clarithromycin and hypoglycemic agents, including insulin, in rare cases, the development of hypoglycemia is possible.

Special instructions:

In the presence of chronic liver diseases it is necessary to conduct regular monitoring of "hepatic" enzymes in blood serum.

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

Form release / dosage:

Tablets, film-coated, 250 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

By 10, 20, 30, 40, 50 or 100 tablets into a polymer container for medicines.

One container or 1, 2, 3, 4, 5, 6, 8 or 10 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 25 eС. Keep out of the reach of children.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002475/09

Date of registration:27.03.2009

Expiration Date:Unlimited

The owner of the registration certificate:OZONE, LLC OZONE, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp24.01.2018

Illustrated instructions

Instructions

Clarithromycin (Clarithromycin)