"Clarithromycin": reviews. Clarithromycin tablets: application

Few facts about the product:

Instructions for use

Price in the online pharmacy website: from 445

Release form, composition and packaging

The drug has several forms: yellow coated tablets of 250 and 500 mg. 14 pieces in a box; small yellow granules in glass vials to obtain 60 ml or 100 ml of suspension.

pharmachologic effect

The drug is classified as an antibiotic of the macrolide group, it works on the principle of blocking protein synthesis. Clarithromycin SR has a wide range of antimicrobial effects. The drug shows high efficiency in the fight against the following microorganisms: gram-positive and gram-negative; intracellular; anaerobic. It should be noted that analogues of Clarithromycin SR also work effectively and with the same therapeutic action... For example, you can use Aziklar, Klacid and Claricar.

Indications

The drug is recommended for the treatment of infectious and inflammatory diseases of the following categories: respiratory tract - sinusitis and pharyngitis; skin - decay of the hair follicles; stomach and duodenum - gastritis and peptic ulcer. According to the instructions, the drug is used to combat infectious diseases that are highly sensitive to the active ingredient: otitis media; tonsillopharyngitis; sinusitis; bronchitis; pneumonia. The drug is used for prophylactic measures for microbacterial infections in patients with AIDS.

Contraindications

The drug is contraindicated for use in the following situations: violation of pigment metabolism; disruption of the kidneys; simultaneous administration of the drug with ergot alkaloids; high sensitivity to fructose; impaired absorption of glucose and galactose; insufficient content of sucrase and isomaltase; first trimester of pregnancy; period of breastfeeding; minor age; high sensitivity to drug ingredients; high susceptibility to antibiotics of this group. The possibility of using the drug in the second and third trimesters of pregnancy is determined on an individual basis. Children under 12 years old, as well as those whose body weight does not exceed 33 kg, are prohibited from taking medicine in tablets.

Method of administration and dosage

The medicinal product is intended for administration to adults and adult children at a dosage of 500 mg with meals. If necessary, an increase to 1000 mg is allowed, or the dosage can be divided twice every 12 hours. The duration of treatment is 1-2 weeks. The tablets are not divided, but consumed completely, washed down with plenty of water. For sinusitis and other severe infections, 500 mg is usually prescribed every 12 hours. The course lasts up to 14 days. For the treatment of gastritis and ulcers, a dose of 250-500 mg is determined twice a day for 7 days in combination with other drugs. In the treatment of infectious diseases and preventive measures 500 mg is prescribed every 12 hours and the course lasts 6 months. For children under 12 years of age, a suspension is prescribed, which is made at the rate of 15 mg per kg of the child's weight. Take this dose, dividing into 2 doses, each time drinking plenty of water. The granules contained in the suspension should not be chewed due to their bitter taste. The drug for administration under the age of 12 years must be administered orally using a dispenser that holds 5 ml of suspension, which is equal to 125 mg of the active substance. After use, the syringe must be thoroughly rinsed and dried. The average duration of the course is 1-2 weeks based on the indications. In order to prepare a suspension, it is necessary to shake the bottle, add 10 ml of water and stir until the granules dissolve. After that, add another 32 ml of water to the mark on the vial and mix thoroughly, shaking vigorously.

Pregnancy and lactation

The drug is contraindicated for use in the first trimester of pregnancy and during breastfeeding.

Side effects

The use of the drug can contribute to the manifestation of negative effects: 1. Very often - headaches, attacks of anxiety and fear, the urge to nausea and vomiting, diarrhea. 2. Less commonly - candidal stomatitis, inflammation of the tongue, darkening of the tongue and teeth, pain in the joints and muscles, rash and urticaria, decreased sensitivity and change in taste. 3. Very rarely - attacks of insomnia, inflammatory process choroid eyes, attacks of hallucinations and psychosis, increased heart rate, impaired renal function. Isolated cases indicate that hearing loss is possible, which, as a rule, goes away immediately after drug withdrawal.

Overdose

In case of overdose medicinal product the following symptoms may appear: attacks of nausea and vomiting; stomach ache; diarrhea; headache; confused consciousness. All these side effects easily eliminated with gastric lavage and the use of symptomatic therapy.

Drug interactions

The simultaneous use of this drug with the following drugs may cause undesirable consequences: 1. Midazolam, Lovastatin, Phenytoin and other drugs of this action - there may be an increase in the content of their active substance in the blood. 2. Corbamazepig and Diconsin - an increase in the concentration of their active component in plasma. 3. Warfarin - enhancing the effect of the action. 4. Quinidine and Disopyramide - manifestations of gastric tachycardia. 5. Ergotamine or Dihydroergotamine - enhancement of the effect with the manifestation of spasmodic vascular attacks. 6. Ritonavir - increasing the concentration of clarithromycin in the blood. 7. Cisapride and Pimozide - manifestations of arrhythmia and gastric tachycardia. 8. Zidovudine in the treatment of HIV-infected - a decrease in the content of the drug in the blood.

special instructions

It is necessary to take the drug in case of impaired kidney and liver function with maximum caution and strictly under the supervision of the attending physician. With the simultaneous administration of this drug with Warfarin and other anticoagulant drugs, prothrombin time should be monitored regularly. The drug does not have any adverse effect, which can be dangerous when driving a car or other complex mechanisms.

Storage conditions and periods

It is recommended to store the medicinal product in a place that children do not have access to, as well as where sunlight and dry heat... Storage temperature should not exceed + 25 ° С. You can buy Clarithromycin SR in Moscow and in any other region at a pharmacy, including delivery.

Klacid ® and Klacid ® CP (lat. Klacid ® and Klacid ® SR) - antibiotics of the macrolide class. The active ingredient is clarithromycin. In gastroenterology Klacid ® known as one of the antibiotic drugs used in the composition complex therapy during eradication Helicobacter pylori.

Dosage forms of Klacid

Klacid and Klacid SR are available in the following dosage forms:

• Klacid SR - tablets prolonged action yellow, oval, film-coated, containing 500 mg of clarithromycin (release clarithromycin gradually over the time the tablet passes through the gastrointestinal tract).
• Klacid - tablets immediate release yellow, oval, coated, containing 250 mg of clarithromycin.
• Klacid - tablets immediate release light yellow oval, coated, containing 500 mg of clarithromycin.
• Klacid is a powder for suspension for oral administration, white or almost white, granular, with a fruity aroma, 5 ml of the finished suspension contains 125 mg of clarithromycin ("125 mg / 5 ml").
• Klacid - powder for preparation of suspension for oral administration, granules of white or almost whitewith a fruity aroma, 5 ml of the finished suspension contains 250 mg of clarithromycin ("250 mg / 5 ml").
• Klacid - lyophilisate for preparation of solution for infusion; from white to almost white, with a faint aromatic odor; one bottle contains 500 mg of clarithromycin.

Indications for the use of Klacid SR of prolonged action

Klacid SR and Klacid in the form of a lyophilisate for the preparation of a solution for infusion is used to treat infectious and inflammatory diseases caused by microbes sensitive to the drug: lower and upper divisions respiratory tract and ENT organs (bronchitis, pneumonia, pharyngitis, sinusitis, etc.), skin and soft tissues, including folliculitis, inflammation of the subcutaneous tissue, erysipelas.

Indications for the use of Klacid suspension

Klacid in the form of a suspension is used to treat the infectious diseases listed above in the section "Indications for the use of Klacid SR with prolonged action", as well as mycobacterial infections, widespread or localized, caused by Mycobacterium avium and Mycobacterium intracellulare and localized infections caused by Mycobacterium chelonae, Mycobacterium fortuitum and Mycobacterium kansasii.

In addition, Klacid in the form of a suspension is used as part of eradication schemes Helicobacter pylori and in the prevention of recurrence of duodenal ulcers (only in combination with other drugs!).

Indications for use of Klacid immediate release

Klacid in tablets of immediate release is used for the treatment of infectious diseases listed above in the sections "Indications for the use of Klacid SR of prolonged action" and "Indications for the use of a suspension of klacid", as well as prevention of the spread of infection caused by the complex Mycobacterium avium, HIV-infected patients with the content of T-helper lymphocytes no more than 100 in 1 mm 3 and odontogenic infections.

Application procedure and doses Clacid tablets (immediate release)

Klacid tablets are taken orally, without being linked to food intake. Adults, unless the doctor prescribes otherwise, take one Clacid tablet containing 250 mg of clarithromycin, 2 times a day. In more severe cases, the dose is doubled. Duration of treatment is from 5 to 14 days.

Patients with Cl creatinine less than 30 ml / min are prescribed one tablet of 250 mg once a day, or for more severe infections - one tablet of 250 mg 2 times a day for no more than 14 days.

For the treatment of mycobacterial infections, Klacid is taken based on a dose of 500 mg of clarithromycin 2 times a day. The duration of treatment is determined by the doctor

For common infections caused by Mycobacterium avium, in AIDS patients: treatment with Klacid (in combination with other antimicrobial drugs) continues as long as there is positive effect.

Klacid during eradication Helicobacter pyloriand relapse prevention peptic ulcer are taken only as part of a complex of drugs, the dose and the procedure for taking depends on the applied "scheme" of eradication (see the article "Clarithromycin" or "Standards for the diagnosis and treatment of acid-dependent and Helicobacter pylori-associated diseases (fourth Moscow agreement)").

Professional medical publications regarding the use of Klacid for the eradication of Helicobacter pylori

• Maev I.V., Samsonov A.A., Andreev N.G., Kochetov S.A. Clarithromycin as the main element of eradication therapy for diseases associated with Helicobacter pylori infection // Gastroenterology. 2011. No. 1.

On the site in the literature catalog there is a section "Antibiotics used in the treatment of gastrointestinal diseases" containing articles on the use of antimicrobial agents in the treatment of organ diseases digestive tract.

Application procedure and doses Clacid in suspension

The suspension of Klacid is prepared by gradually adding water to the bottle with granules to the level of the mark, after which the bottle is shaken. You should get 60 ml of a suspension of clacid containing 125 mg of clarithromycin in 5 ml, or 100 ml of a suspension containing 250 mg of clarithromycin in 5 ml. The Klacid suspension is stored at room temperature for up to two weeks. The suspension is taken orally, with milk, with or without food. Before use, the bottle with Klacid suspension must be shaken well.

Dosage of Klacid suspension in the treatment of non-mycobacterial infections in children... The duration of treatment is 5-7 days, depending on the pathogen and the patient's condition. A single dose of a suspension of clacid is calculated based on 7.5 mg of clarithromycin per kg of patient weight. The calculated dose is taken twice a day. The maximum dose of clacid is 500 mg of clarithromycin 2 times a day. In order to determine a single dose of clacid suspension, one can proceed from the following:

• for children weighing up to 8 kg - proceed from the above 7.5 mg clarithromycin per kg of body weight
• for children weighing from 8 to 11 kg - take half a teaspoon (5 ml) of a suspension of clacid containing 125 mg of clarithromycin per 5 ml ("125 mg / 5 ml") twice a day
• for children weighing from 12 to 19 kg - take a teaspoon of Clacid suspension "125 mg / 5 ml" or half a teaspoon of Clacid suspension containing 250 mg of clarithromycin per 5 ml ("250 mg / 5 ml") twice a day
• for children weighing from 20 to 29 kg - take one and a half teaspoon of clacide suspension "125 mg / 5 ml" or 0.75 teaspoon of clacide suspension "250 mg / 5 ml" twice a day
• for children weighing from 30 to 40 kg - take 2 teaspoons of Klacid suspension "125 mg / 5 ml" or one teaspoon of Klacid suspension "250 mg / 5 ml" twice a day

Dose of Klacid suspension in children with mycobacterial infections calculated on the basis of taking 15-30 mg of clarithromycin per kg of child weight per day in two divided doses. Klacid is taken as long as the clinical effect persists.

Application procedure and doses Klacida SR (prolonged release)

Swallowing tablets of Klacid SR whole, without cutting, without chewing, without crushing, during meals, one tablet once a day. For severe infections, take two tablets once a day. The duration of treatment is from 5 to 14 days.

The use of Klacid during pregnancy, lactation and in children

The use of Klacid in the first trimester of pregnancy is contraindicated. In the II and III trimesters of pregnancy, taking Klacid is possible if the expected benefit to the mother outweighs the potential risk to the fetus.

When treating the mother with Klacid, breastfeeding should be stopped.

Due to the lack of data on efficacy and safety, it is not recommended to take Klacid by children under the age of three years, Klacid SR - up to 18 years.

Other medicines with active ingredient clarithromycin

Having (had) registration in Russia: Bacticap, Biotericin, Zimbaktar, Kispar, Klabaks, Klabaks OD, Clarbact, Clarithromycin-Verte, Clarithromycin-J, Clarithromycin Zentiva, Clarithromycin Protech, Clarithromycin Pfizer, Clarithromycin Clarithromycin Clarithromycin-OBL, Clarithromycin-OBL, Clarithromycin-SR , Claritrosin, Claricin, Claricite, Claromine, Clasine, Clerimed, Coater, Lecoclar, Mitsetinum, Romiklar, Seydon-Sanovel, SR-Claren,

Certainly infectious diseases bacterial origin it is difficult to consider it a rarity. And quite often doctors in such cases prescribe a semi-synthetic drug "Clarithromycin". Reviews of this medication are mostly positive, because the remedy really gives the desired result. However, patients are interested in additional information about the composition and rules of taking the drug, as well as the risks and contraindications associated with treatment.

Drug release form

To begin with, it should be noted that "Clarithromycin" is a drug belonging to the group of semi-synthetic antibiotics.

This medicine is available in the form of solid oval biconvex tablets. Their color can be either white or light yellow. Top of the tablets are film-coated. The drug has a not very pleasant bitter taste (when using it, it is better not to try to chew it).

Composition of the medicine

The main active ingredient of the drug is the antibiotic clarithromycin. One tablet may contain 250 or 500 mg of the active substance (this information is indicated on the package).

Propylene glycol, as well as sodium starch glycolate, corn starch, purified talc, microcrystalline cellulose, magnesium stearate, as well as polyethylene glycol 6000 and dyes are used as auxiliary substances in the production of the drug.

Main pharmacological properties

As already mentioned, this medicine widely used to treat bacterial diseases. So in what cases do doctors prescribe the drug "Clarithromycin", the use of which is widespread? The indications are as follows:

• Upper respiratory tract infections, including sinusitis, laryngitis, tonsillitis and pharyngitis.
• Lower respiratory tract diseases. In particular, the drug is effective for pneumonia (including the atypical form), acute bronchitis and chronic inflammation bronchi during an exacerbation.
• Bacterial infections of soft tissues and skin, including wound infection, folliculitis, impetigo, furunculosis.
• Indications for admission are inflammatory diseases stomach and duodenum. By the way, this drug in combination with other drugs is used when Helicobacter pylori is active.
• In otolaryngology, the medicine can be used to treat otitis media.
• Indications include some sexually transmitted infections, including chlamydia.

The drug "Clarithromycin": instructions for use

It should be noted right away that it is strictly forbidden to use this drug without permission. Only the attending physician can make an accurate diagnosis, determine the individual characteristics of the body and prescribe the appropriate dosage.

So how do you take Clarithromycin? The instruction contains only general recommendations. Adults, as well as children over twelve years of age, are recommended to take 250-500 mg of the active substance twice a day. In the presence of severe infectious diseases, the daily dose can be increased to 500-1000 mg. In any case, the maximum amount of active substance that an adult can take per day is 2 g. Exceeding the recommended amount can lead to an overdose.

As for the duration of the course of treatment, here the doctor also decides. However, it is not recommended to take this antibiotic for more than two weeks.

Are there any contraindications?

Of course, like almost any other antibacterial drug, "Clarithromycin" has some contraindications:

• To begin with, it should be noted that the drug is not prescribed for patients with severely impaired liver function.
• Porphyria is also a contraindication.
• The drug is not used to treat people with a history of hepatitis.
• We should also talk about pregnancy. This medication is not used during the first trimester. In the future, the decision to use this drug is made by the attending physician.
• If you have kidney disease or renal failure treatment is carried out exclusively in a hospital setting. The dosage for such diseases is halved, and the patient must be constantly under the supervision of doctors.
• Before starting to use the medicine, the patient must inform the doctor about the drugs he is taking. Clarithromycin is by no means prescribed concurrently with drugs such as Pimozide, Cisapride and Astemizole.
• Naturally, an increased allergic sensitivity of a person to any of the constituent components of "Clarithromycin" is considered a contraindication.

Possible side effects

IN modern medicine quite often the drug "Clarithromycin" is used. Reviews indicate that side effects from taking it are relatively rare. Nevertheless, complications are still possible, so you should familiarize yourself with their list:

• From the side digestive system sometimes there is nausea, abdominal discomfort, as well as vomiting and diarrhea (in the most severe cases, even with blood). Much less common are stomatitis, glossitis, as well as jaundice and pseudomembranous enterocolitis.
• Disruptions in work are possible nervous system... In particular, some patients complain of headaches, weakness and dizziness. Less commonly, there is increased anxiety, nightmares, disorientation, psychosis, hallucinations.
• The circulatory system can also be exposed to the drug, but this is relatively rare. Side effects include leukopenia, thrombocytopenia, and ventricular tachycardia, arrhythmia, flickering.
• Some patients develop during therapy allergic reactions, which are accompanied by the appearance of skin rash and itching, less often - malignant exudative erythema.
• Among other adverse reactions, possible hypoglycemia, as well as the development of resistance of pathogenic microorganisms to this drug.

In any case, if you have any deterioration in well-being, you should consult a doctor. Perhaps the specialist will decide to cancel the Clarithromycin drug. Of course, there are analogues of the drug, so you can choose any of them if necessary.

Overdose and medical care for patients

Many patients are interested in the question of whether an overdose of the drug "Clarithromycin" is possible. Reviews confirm that this happens relatively rarely. However, this possibility should not be ignored.

Overdose is accompanied by disturbances in the normal functioning of the digestive tract - patients complain of nausea, vomiting, severe pain in the abdomen and diarrhea. Often, against the background of the use of too large doses of the drug, a severe headache develops, confusion is observed.

A patient with similar symptoms should be urgently taken to the hospital. First of all, gastric lavage is performed. Further treatment is symptomatic, since dialysis is ineffective in this case.

Can the drug be used to treat children?

Of course, in modern pediatrics, both the drug itself and some analogues of the drug "Clarithromycin" are used. Suspension "Klacid", for example, is suitable for treating young children preschool age and even newborns. The dosage of this drug is determined individually, but in most cases it is calculated based on the baby's body weight - 7.5 mg of active substance per kilogram of body twice a day. The duration of therapy is 5-10 days (depending on the severity of the child's condition).

Children over 12 years old can be prescribed Clarithromycin tablets. You need to take 250 mg of the active substance (this is one tablet) twice a day. It is advisable to drink the drug with plenty of water.

But it should be understood that the medicine "Clarithromycin" for children can be prescribed only by the attending physician after a thorough diagnosis. In no case should you give your child pills without permission, as this can lead to not too pleasant consequences.

How much does the medicine cost?

There is another important question that patients who are going to start treatment with Clarithromycin are interested in - the price of the drug. It should be noted right away that the cost of a medicine depends on many factors, including the manufacturer, the form of release, as well as the financial policy of the pharmacy, etc.

So how much does Clarithromycin cost? The price of the drug with a dosage of 250 mg on average ranges from 200 to 300 rubles. But the tablets, which contain 500 mg of the active substance, are more expensive - about 400-500 rubles.

Are there any effective analogues?

Some patients are wondering if Clarithromycin can be substituted. There are certainly analogues. For example, the most popular drug in this group is Klacid, which is available in the form of tablets and suspensions.

In addition, such drugs as "Klabel", "Aziklar", "Klabaks", "Fromilin", Klerimed "and" Lekoklar "are considered effective. All of these drugs contain the same active substance and have similar pharmacological properties.

The drug "Clarithromycin": reviews

Of course, the reviews of people who have been treated with Clarithromycin are also important for patients. This drug is often prescribed for certain infectious diseases... Most patients note the effectiveness of the drug. Indeed, the symptoms disappear after 1-3 days after the start of treatment.

Nevertheless, there is a possibility of dysbiosis development - treatment with almost any antibiotic is associated with this problem. Therefore, at the reception, be sure to ask your doctor about how to protect the intestinal microflora.

On the other hand, of course, there are patients who have not been helped by this drug or have caused severe side effects. In any case, it should be understood that treatment depends partly on the individual characteristics of the organism.

IN medical practice often there is a need to prescribe oral drugs with high antibacterial activity and a wide spectrum of action. These drugs include the macrolide Clarithromycin 500 mg, the instructions for use for which indicate large group pathogenic microorganisms sensitive to this antibiotic.

Pharmacological properties

Clarithromycin belongs to the group of macrolide antibiotics, the first representative of this family is erythromycin, obtained by American scientists back in 1952. Compared to erythromycin, modern macrolide has several advantages: a wider spectrum of action, fewer side effects, and a low minimum inhibitory concentration.

The antibacterial effect of Clarithromycin develops as a result of the effect of the substance on the ribosomal structures of pathogenic microorganisms and inhibition of their vital functions. The drug is active against aerobic and anaerobic bacteria (both gram-positive and gram-negative). Staphylococci, Haemophilus influenzae, mycoplasma, chlamydia, mycobacteria, listeria, peptococci, clostridia, spirochetes, and Helicobacter pylori are highly sensitive to this antibiotic.

After internal administration, the active substance is rapidly absorbed in the gastrointestinal tract, food consumption does not affect the degree of absorption of the drug. Since food does not alter the bioavailability of Clarithromycin, the drug can be taken at any time of the day, regardless of diet.

The antibiotic belongs to prescription drugs, in pharmacies it is present in two dosages: 250 and 500 mg. The price of Clarithromycin 500 mg is higher than the cost of macrolide at a dose of 250 mg by only 30-50 rubles. If you look at how much Clarithromycin 500 mg costs in pharmacies in St. Petersburg, you can see that the price of domestic tablets in the amount of 14 pieces per package starts at 245 rubles.

Most drugs with clarithromycin as the active ingredient have the same name, some manufacturers add a proprietary prefix, such as Clarithromycin-Teva.

You can also purchase clarithromycin under the following trade names: Fromilid, Klacid, Klabaks, Lecoclar.

Indications and contraindications

The instructions for use of Clarithromycin 500 mg tablets say that the drug is used for infections caused by microorganisms sensitive to the active substance. Therefore, before treatment, it is necessary to inoculate the microflora and make an analysis for its sensitivity to antibiotics. In practice, this does not always happen, due to the wide spectrum of action of macrolide, the infections listed in the instructions are successfully cured.

Antibiotic indications:

• diseases of the upper respiratory tract: pharyngitis, tonsillitis.
• sinusitis.
• bronchitis, pneumonia.
• soft tissue infections.
• odontogenic infections.
• stomach ulcer (if necessary, the destruction of Helicobacter pylori).
• infections caused by certain types of mycobacteria.

Contraindications to the use of the drug are hypersensitivity to macrolides, severe liver and kidney disease.

The combined use of an antibiotic with medicines from the group of statins, some antipsychotic drugs. Clarithromycin changes the pharmacokinetics of antiarrhythmic and hypoglycemic drugs, omeprazole, sildenafil, itraconazole, therefore, when taken simultaneously with these drugs, careful medical monitoring of patients is necessary.

Macrolide is not prescribed to pregnant women, due to the penetration of the drug into breast milk for the duration of the treatment, the child's mother is transferred to artificial feeding. The antibiotic in tablet form is not used to treat children under 12 years of age; young children are given an oral suspension of Clarithromycin.

Mode of application

Clarithromycin is taken orally regardless of food, observing the same intervals between tablet doses. The dosage and duration of treatment depend on the severity of the infection and the type of pathogen.

• For mild infections - 250 mg 2 times a day for 6-14 days.
• For severe infections - 500 mg 2 times a day for at least two weeks.
• For odontogenic infections - 250 mg 2 times a day for 5 days.
• For eradication, Halicobacter pylori - 500 mg 2 times a day simultaneously with amoxicillin and omeprazole for 7-10 days.

If the doctor has prescribed Clarithromycin CP 500, the instructions for use of this drug indicate that these are extended-release tablets. Active substance Clarithromycin SR is released in the body gradually throughout the day, so the drug can be taken once a day, one tablet at a dosage of 500 mg (in severe cases, the doctor prescribes 2 tablets).

Side effects

The most common adverse reactions with clarithromycin treatment are nausea, abdominal pain, diarrhea... With long-term treatment, candidiasis of the mucous membranes of the oral cavity and intestines, allergic skin rashes, leukopenia, loss of appetite, insomnia, dizziness, impaired liver and kidney function appear.

Severe side effects during treatment with Clarithromycin are rare, usually patients tolerate treatment well without presenting any complaints.

Instructions

Tradename

Klacid 

International non-proprietary name

Clarithromycin

Dosage form

Coated tablets,500 mg

Composition

One pill, sheathedcontains:

active substance - clarithromycin 500 mg

excipients: croscarmellose sodium, microcrystalline cellulose, silicon dioxide,povidone, stearic acid, magnesium stearate,talc.

shell composition: hypromellose, sorbitan monooleate, propylene glycol, titanium dioxide (E171), vanillin, yellow dye (quinoline yellow) (E 104)aluminum varnish, hydroxypropyl cellulose, sorbic acid.

Description

Oval tablets, film-coated, pale yellow.

Pharmacotherapeutic group

Antibacterial drugs for systemic use. Macrolides, lincosamides and streptogramins. Macrolides. Clarithromycin.

ATX code J01 FA09

Pharmacological properties

PharmacokineticsAbsorption

Pharmacokinetics of the drug Klacid® has been extensively studied in experimental animals and adults. These studies have shown that clarithromycin is completely and rapidly absorbed. The absolute bioavailability is about 50%. With repeated administration of the drug, unexpected cumulation is not detected or is determined in small quantities. In this case, the nature of metabolism in the human body does not change. Eating food immediately before administration of the drug increases the bioavailability of clarithromycin by an average of 25%. In general, this increase is insignificant and of little clinical significance at the recommended dosing regimens. Therefore, clarithromycin can be administered with or before meals.

Distribution, biotransformation and elimination

In vitro

Research in vitro showed that clarithromycin binds to human plasma proteins at an average level of about 70%, at clinically significant concentrations from 0.45 μg / ml to 4.5 μg / ml. The decrease in binding to 41% at 45.0 μg / ml suggested that the binding sites could be saturated, but this only occurred at concentrations much higher than the therapeutic concentration of the drug.

The results of animal studies showed that the levels of clarithromycin in all tissues, except the central nervous system, were several times higher than the levels of the drug circulating in the blood. The highest concentrations were usually found in the liver and lungs, where the tissue / plasma ratio reached 10-20.

Healthy subjects

With a dosage regimen of 250 mg 2 times a day, the equilibrium maximum concentration (Cmax ) was reached after 2-3 days and averaged approximately 1 μg / ml for clarithromycin and 0.6 μg / ml for 14-OH-clarithromycin, respectively. The half-lives of the parent drug and metabolite are 3-4 hours and 5-6 hours, respectively. With a dosage regimen of 500 mg 2 times a day Cmax the equilibrium state of clarithromycin and 14-OH-clarithromycin was achieved after taking the 5th dose of the drug. After taking the 5th and 7th dosesC max Clarithromycin in the equilibrium state in the average state was 2.7 and 2.9 μg / ml, and 14-OH-clarithromycin - 0.88 and 0.83 μg / ml, respectively. The half-life of the parent drug at a dose of 500 mg was 4.5-4.8 hours, and that of 14-OH-clarithromycin was 6.9-8.7 hours. At steady-state, the concentration of 14-OH-clarithromycin does not increase in proportion to the dose of clarithromycin, and the half-lives of clarithromycin and its hydroxylated metabolite tended to be lengthened with higher doses. This nonlinear pharmacokinetics of clarithromycin, together with the cumulative reduction in the formation of 14-hydroxylation and N-demethylation products at higher doses, indicate that nonlinear metabolism of clarithromycin becomes more pronounced at higher doses.

In adults who received a single dose of clarithromycin 250 mg or 1200 mg orally, excretionwith urine was 37.9% of the low dose of the drug and 46.0% of its high dose. Intestinal excretion was 40.2% and 29.1% of the respective clarithromycin doses (including subject with only one fecal sample containing 14.1% of the drug).

The patients

Clarithromycin and its 14-OH metabolite are readily distributed in tissues and body fluids. Limited data from a small patient study suggest that clarithromycin concentrations in cerebrospinal fluid after oral administration, it is insignificant (in particular, only 1-2% of the concentration in serum in the cerebrospinal fluid with normal permeability of the blood-brain barrier). Tissue concentrations are usually several times higher than serum concentrations.

Liver dysfunction

In a study comparing a group of healthy volunteers with a group of patients with impaired liver function who took 250 mg of immediate-release clarithromycin twice daily for two days and single dose 250 mg on the third day, equilibrium plasma concentrations and systemic clearance of clarithromycin did not differ significantly in both groups. In contrast, the equilibrium concentrations of 14-OH -metabolite were significantly lower in the group of patients with impaired liver function. This decreased metabolic clearance of the parent compound by 14-hydroxylation was partially compensated by the increased renal clearance of the parent drug, resulting in comparable equilibrium concentrations of the parent drug in patients with impaired liver function and healthy volunteers. These results indicate that no dose adjustment is required in individuals with moderate or severe liver damage but normal renal function.

Impaired renal function

A study was conducted to evaluate and compare the pharmacokinetic profile of multiple 500 mg oral doses of immediate-release clarithromycin in patients with normal and reduced renal function. Plasma concentrations, half-life,Cmax and Cmin for clarithromycin and its 14-OH -metabolite were higher, andAUC - more in patients with impaired renal function. The elimination constant and urinary excretion were lower. The degree of change in these parameters depends on the degree of renal dysfunction: the more severe the kidney damage, the more significant the difference (see section "Dosage and Administration").

Elderly patients

A study was also conducted to assess and compare the safety and pharmacokinetic profile of oral multiple dose clarithromycin 500 mg in healthy elderly male and female patients and healthy young male adults. In the group of elderly people, the plasma concentrations of the parent drug and 14-OH -metabolite were higher, and the excretion was slower than in the young group. However, no differences were found between the ratio of renal clearance and creatinine clearance. From these results, it is concluded that any change in pharmacokinetics is associated with renal function, not age per se.

Infections caused by Mycobacterium avium

The equilibrium concentrations of clarithromycin and 14-OH -clarithromycin in adult patients with HIV infection who received clarithromycin at a dose of 500 mg every 12 hours were similar to those in healthy individuals. However, at higher doses that may be required to treat infections caused byMycobacterium avium, clarithromycin concentrations were significantly higher than those observed at usual doses... In adult HIV-infected patients who took the drug at a dose of 1000 and 2000 mg / day in two divided doses, the valuesCmax clarithromycin at equilibrium ranged from 2 to 4 μg / ml and from 5 to 10 μg / ml, respectively. The elimination half-life at these higher doses was lengthened compared to that in healthy people who received normal doses of clarithromycin. Higher plasma concentrations and a longer elimination half-life with the administration of clarithromycin at these doses are associated with non-linear pharmacokinetics of the drug.

Application simultaneously with omeprazole

A pharmacokinetic study of clarithromycin 500 mg 3 times a day and omeprazole 40 mg 1 time a day was carried out. With the introduction of clarithromycin alone at a dose of 500 mg every 8 hours, average valuesCmax were approximately 3.8 μg / ml, and the average valuesCmin were approximately 1.8 μg / ml. Average valuesAUC0-8 clarithromycin was 22.9 μg / h / ml.Tmax and the half-life with the introduction of clarithromycin at a dose of 500 mg 3 times a day was 2.1 hours and 5.3 hours, respectively.

In the same study, when prescribing clarithromycin at a dose of 500 mg 3 times a day with omeprazole 40 mg 1 time a day, an increase in the half-life was observed andAUC0-24 omeprazole. All patients who received combination therapy, mean valuesAUC0-24 omeprazole were 89% higher and the harmonic meanT1 / 2 omeprazole - 34% higher than with omeprazole monotherapy. When prescribing clarithromycin with omeprazoleCmax, Cmin, and AUC0-8 clarithromycin increased by 10%, 27%, and 15%, respectively, compared with the values \u200b\u200bachieved with the use of clarithromycin with placebo.

At steady-state, the concentrations of clarithromycin in the gastric mucosa 6 hours after dosing in the clarithromycin / omeprazole group were approximately 25 times higher than those in the clarithromycin group alone. Mean concentrations of clarithromycin in the stomach tissues 6 hours after taking clarithromycin with omeprazole were approximately 2 times higher than those when using clarithromycin with placebo.

Pharmacodynamics

Clarithromycin is a semisynthetic macrolide antibiotic obtained by replacingCH3 O -groups of hydroxyl (OH ) group in the 6th position of the erythromycin lactone ring. More precisely, clarithromycin is 6-O-methylerythromycin A. This antibiotic is a white or almost white powder with a bitter taste, practically odorless, virtually insoluble in water and slightly soluble in ethanol, methanol and acetonitrile. Its molecular weight is 747.96

Microbiology

Antibacterial effect of the drug Klacid® determined by itsbinding with 5OS -ribosomal subunit of sensitive bacteria and inhibitionprotein biosynthesis.The drug is highly effectivein vitro against standard bacterial strains and strains isolated in clinical practice. It is highly effective against wide range aerobic and anaerobic gram-positive and gram-negative microorganisms. The minimum inhibitory concentration (MIC) of clarithromycin on average perlog 2 dilution is lower than the MIC of erythromycin. Clarithromycinin vitro highly effective againstLegionella pneumophila andMycoplasma pneumoniae . Clarithromycin acts bactericidal againstHelicobacter pylori, clarithromycin activity at neutral pH is higher than at acidic pH.In vitro and in vivo the data indicate the high efficacy of clarithromycin against clinically significant strains of mycobacteria. Research in vitro showed , what strains Enterobacteriaceae and Pseudomonas, like gram-negative bacteria that do not ferment lactose, they are insensitive to clarithromycin.

The activity of clarithromycin against most strains of the microorganisms listed below is shown asin vitroand in clinical practice for diseases listed in the section "Indications for use".

Staphylococcus aureus,

Streptococcus pneumoniae,

Streptococcus pyogenes,

Listeria monocytogenes.

Aerobic gram-negative microorganisms :

Haemophilus influenzae,

Haemophilus parainfluenzae,

Moraxella catarrhalis,

Neisseria gonorrhoeae,

Legionella pneumophila.

Other microorganisms :

Mycoplasma pneumoniae,

Chlamydia pneumoniae (TWAR).

Mycobacteria :

Mycobacterium leprae,

Mycobacterium kansasii,

Mycobacterium chelonae,

Mycobacterium fortuitum,

Mycobacterium avium complex (MAC),which includes Mycobacterium avium, Mycobacterium intracellulare.

Beta-lactamase production does not affect the effectiveness of clarithromycin.

Most methicillin- and oxacillin-resistant staphylococcal strains are not sensitive to clarithromycin.

Helicobacter:

H. Pylori.

In cultures prepared prior to therapy,H. pylori and before starting treatment, the minimum inhibitory concentration was determined in 104 patients. Of these, 4 patients had clarithromycin-resistant strains.H. pylori, 2 patients had strains with intermediate sensitivity, and 98 patients had isolatesH. pylori were sensitive to clarithromycin.

There are the following data obtainedin vitro, but their clinical significance is not known . Clarithromycin shows activityin vitro for most strains of the following microorganisms; however, the safety and efficacy of clarithromycin in the treatment of clinical infections caused by these microorganisms has not been confirmed by controlled clinical trials.

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 :

Bacteriodes melaninogenicus .

Spirochetes:

Borrelia burgdorferi ,

Treponema pallidum .

Campylobacter :

Campylobacter jejuni .

The main metabolite of clarithromycin in the human body is the microbiologically active metabolite 14-OH -clarithromycin. For most microorganisms, this metabolite is as active or 1-2 times less active than the parent compound, with the exception ofH. influenzae, in relation to which he is twice as active. The original compound and 14-OH -metabolite cause an additive or synergistic effect onH. influenzae in conditions in vitro and in vivo, depending on the strain of bacteria. Experimental data obtained in animal models of infection have shown that clarithromycin is 2-10 times more active than erythromycin.

Indications for use

Clarithromycin is indicated for the treatment of infections caused by susceptible organisms:

Lower respiratory tract infections (bronchitis, pneumonia, etc.)

Upper respiratory tract infections (pharyngitis, sinusitis, etc.)

Skin and soft tissue infections (folliculitis, cellulitis, erysipelas, etc.)

Disseminated or localized mycobacterial infections caused byMycobacterium avium or Mycobacterium intracellulare, localized infections caused byMycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium kansasii;

For the prevention of disseminirovann s infections caused by the complexMycobacterium avium (MAC) in HIV-infected patients with CD count4 - lymphocytes ≤ 100 / mm3 ;

For eradication H. pylori , helping to reduce the recurrence of duodenal ulcer

- treatment of odontogenic infections

Sensitivity tests

Quantitative methods requiring measurement of the zone diameter provide the most accurate estimates of antimicrobial susceptibility of bacteria. One recommended procedure for susceptibility testing uses discs impregnated with 15 μg clarithromycin (Kirby-Bauer diffusion test); the diameter of the zone of inhibition for this disc correlates with the values \u200b\u200bof the minimum inhibitory concentration for clarithromycin. The minimum overwhelming concentration is determined by dilution in broth or agar.

For these procedures, a susceptibility report from the laboratory indicates that the infectious organism is most likely to respond to therapy. A report with the word “resistant” indicates that the infectious organism is unlikely to respond to therapy. A report with the words “intermediate sensitivity” suggests that the therapeutic effect of this drug may be questionable or the organism will be sensitive if higher doses are used (intermediate sensitivity is also referred to as moderate sensitivity).

See specific country or region specific information for absolute cut-off ranges for sensitivity, persistence and intermediate sensitivity.

Method of administration and dosage

Adults

The usual recommended dose of clarithromycin for adults and children over 12 years of age is 250 mg per tablet twice a day. For more severe infections, the dose can be increased to 500 mg twice a day. The usual duration of treatment is 5 to 14 days, except for the treatment of community-acquired pneumonia and sinusitis, which require 6 to 14 days of therapy.

Mycobacterial infections

Treatment of disseminated MAC infections in AIDS patients should be continued until clinical and microbiological effects are demonstrated. Clarithromycin should be used in combination with other antimycobacterial drugs.

Treatment of other non-tuberculous mycobacterial infections should be continued at the discretion of the attending physician.

Odontogenic infections

For the treatment of odontogenic infections, the usual doseclarithromycin is 250 mg 2 times a day for 5 days.

In patients with peptic ulcer caused byH. pylori -infection, clarithromycin can be administered at a dose of 500 mg 2 times a day in combination with other necessary antimicrobials and proton pump inhibitors for 7-14 days in accordance with national or international recommendations for eradicationH. pylori .

Renal failure

In patients with severe renal impairment (creatinine clearance less than 30 ml / min), the dose of clarithromycin should be reduced by half and should be 250 mg once a day or 250 mg twice a day for more severe infections. These patients should not be treated for more than 14 days.

Children

Application of the drug Klacid® in children under 12 years of age has not been studied.

Side effects

The most frequent and common adverse reactions during treatment with Klacid® adults and children have abdominal pain, diarrhea, nausea, vomiting and taste distortion. These adverse reactions usually mild and consistent with the known safety profile of macrolide antibiotics. During clinical research there were no significant differences in the incidence of these gastrointestinal adverse reactions between groups of patients who had or did not have mycobacterial infections.

Below are the adverse reactions that have occurred during clinical trials and post-marketing application of various dosage forms and dosages of the drug Klacid® ... Adverse reactionsat least, probably related to clarithromycin, distributed by organ system and by frequency of occurrence: very common (≥1 / 10), often (≥ 1/100 to<1/10), нечасто (≥ 1/1000 до <1/100), с неизвестной частотой (побочные реакции, выявленные при постмаркетинговом наблюдении, частоту определить невозможно из имеющихся данных). В пределах каждой группы по частоте побочные реакции представлены в порядке убывания тяжести проявлений, если тяжесть удалось оценить.

Often

phlebitis at the injection site1

Often

≥ 1/100 to<1/10

Insomnia

Headache

Dysgeusia, taste impairment

Vasodilation 1

Nausea, abdominal pain, vomiting, dyspepsia, diarrhea

Abnormal liver function tests

Rash, hyperhidrosis

Pain at the injection site1 , inflammation at the injection site1

Infrequently

≥ 1/1000 to<1/100

Cellulite 1 , candidiasis, gastroenteritis2

Infection 3 , vaginal infection

- leukopenia, neutropenia4, thrombocythemia 3, eosinophilia 4

Anaphylactoid reactions1 , hypersensitivity

Anorexia, decreased appetite

Anxiety, anxiety and agitation3

Loss of consciousness1, dyskinesia 1 , dizziness, drowsiness, tremors

Vertigo, hearing impairment, ringing in the ears

Heart failure1 , atrial fibrillation1 , lengthening of the QT interval on the ECG, extrasystoles1 , palpitations

Asthma 1 , nose bleed2 , pulmonary embolism1

Esophagitis 1 , gastroesophageal reflux disease2 , gastritis, proctalgia2 , stomatitis, glossitis, bloating4 , constipation, dry mouth, belching, flatulence

Cholestasis 4, hepatitis 4 , increasing the level of ALT, AST, GGT4

Bullous dermatitis1 , itching, urticaria, maculopapular rash3

Muscle spasms3 , musculoskeletal rigidity1, myalgia 2

Increased blood creatinine1 , increased blood urea1

Malaise 4, fever 3 , asthenia, chest pain4, chills 4, fatigue 4

Change in the albumin-globulin ratio1 increasing the level of alkaline phosphatase in the blood4 , increased blood lactate dehydrogenase levels4

Frequency unknown *

(frequency cannot be determined from available data)

Pseudomembranous colitis, erysipelas

Agranulocytosis, thrombocytopenia

Anaphylactic reactions, angioedema

Psychoses, confusion, depersonalization, depression, disorientation, hallucinations, nightmares, mania

Convulsions, ageusia, parosmia, anosmia, paresthesia

Loss of hearing

Pirouette ventricular tachycardia (torsade s de pointes ), ventricular tachycardia, ventricular fibrillation.

Hemorrhage

Acute pancreatitis, discoloration of the tongue, discoloration of the teeth

Hepatic failure, hepatocellular jaundice

Stevens-Johnson syndrome, toxic epidermal necrolysis, drug-induced skin reaction accompanied by eosinophilia and systemic manifestations (DRESS), acne

Rhabdomyolysis 2 **, myopathy

Renal failure, interstitial nephritis

Increased international normalized ratio, increased prothrombin time, urine discoloration.

* Frequency not known as these reactions were reported voluntarily from an unspecified patient population. It is not always possible to accurately establish their frequency or a causal relationship with the drug intake. Total experience with clarithromycin is over 1 billion patient-days.

** In some reports of rhabdomyolysis, clarithromycin has been prescribed concurrently with other drugs known to be associated with rhabdomyolysis (such as statins, fibrates, colchicine, or allopurinol).

1. Adverse reactions have been reported only for the powder formulation for solution for infusion.

2. Adverse reactions were reported only for the extended release tablet form.

3. Adverse reactions have been reported only for the granule formulation for oral suspension.

4. Adverse reactions were reported only for the immediate-release tablet formulation.

The frequency, type and severity of adverse reactions in children are expected to be the same as in adults.

Patients with impaired immune systems In AIDS patients and other patients with impaired immune systems, who have used high doses of clarithromycin for a long time to treat mycobacterial infections,it is not always possible to distinguish between adverse reactions associated with the use of the drug and symptoms of the underlying or concomitant diseases. In adult patients who received Klacid® at a daily dose of 1000 mg, the most common side effects were nausea, vomiting, taste perversion, abdominal pain, diarrhea, rash, bloating, headache, constipation, hearing impairment, increased serum AST and ALT. Uncommon: dyspnea, insomnia, and dry mouth. These patients with compromised immune systems were evaluated for laboratory parameters, analyzing their significant deviations from the normative indicators (i.e., extreme upper or lower limits) for certain tests. According to this criterion, 2-3% of patients who received 1000 mg of clarithromycin per day experienced a significant increase in AST and ALT levels and a significant decrease in the number of leukocytes and platelets in the blood. A smaller percentage of patients also had an increase in blood urea levels.

Contraindications

Hypersensitivity to macrolide antibiotics or to any auxiliary components of the drug.

The concomitant use of clarithromycin and any of the following drugs is contraindicated: astemizole, cisapride, pimozide, terfenadine, as this can lead to prolongation of the QT interval and the development of arrhythmias, including ventricular tachycardia, ventricular fibrillation and ventricular tachycardia of the "pirouette" type ( torsades de pointes) (see section "Drug Interactions").

The simultaneous use of clarithromycin and ergot alkaloids (eg, ergotamine, dihydroergotamine) is contraindicated because it can lead to poisoning with ergot alkaloids (see section "Drug interactions").

Concomitant oral administration of clarithromycin and midazolam is contraindicated (see Drug Interactions).

Clarithromycin should not be used in patients with a history of lengthening of the QT interval (congenital or established acquired prolongation of the QT interval) or ventricular arrhythmias, including ventricular tachycardia of the "pirouette" type ( torsades de pointes) (see "Drug interactions" and "Special instructions").

Clarithromycin should not be administered to patients with hypokalemia (risk of prolongation of the QT interval).

Clarithromycin should not be used in patients with severe hepatic impairment with concomitant renal impairment.

Clarithromycin should not be used concomitantly with HMG-CoA reductase inhibitors (statins), which are extensively metabolized by CYP3A4 (lovastatin or simvastatin), due to the increased risk of myopathy, including rhabdomyolysis (see section “ special instructions»).

Clarithromycin (and other potent CYP3A4 inhibitors) should not be used concomitantly with colchicine (see section "Drug Interactions" and "Special Instructions").

Concomitant administration with ticagrelor or ranolazine is contraindicated.

Children under 12 years old

Drug interactions

The use of the following drugs is strictly contraindicated due to the possible development of severe consequences of the interaction

Cisapride, pimozide, astemizole, and terfenadine .

Increased cisapride levels have been reported in patients receiving Clacid® and cisapride at the same time. This can lead to lengthening of the intervalQT and the appearance of arrhythmias, including ventricular tachycardia, ventricular fibrillation and pirouette-type ventricular tachycardia (torsades de pointes). Similar effects have been reported in patients taking

Klacid ® and pimozide at the same time (see section "Contraindications").

Macrolides interfere with the metabolism of terfenadine, causing an increase in blood levels of terfenadine, sometimes accompanied by arrhythmias such as an increase in the intervalQT , ventricular tachycardia, ventricular fibrillation, and pirouette ventricular tachycardia (torsades de pointes) (see section "Contraindications"). In a study involving 14 healthy volunteers, the simultaneous use of clarithromycin and terfenadine led to a 2-3-fold increase in the serum level of the acid metabolite terfenadine and an increase in the intervalQT that did not cause any clinically significant effect.

Similar effects were noted with the simultaneous use of astemizole and other macrolides.

Ergot alkaloids ... Post-marketing studies show that the simultaneous administration of clarithromycin and ergotamine or dihydroergotamine leads to the toxic effect of ergot, manifested in the form of vasospasm, ischemia of the extremities and other tissues, including the central nervous system.Simultaneous administration of the drug Klacid® and ergot alkaloids are contraindicated (see section "Contraindications").

Oral midazolam

With the simultaneous use of midazolam and clarithromycin tablets (500 mg twice a day),AUC midazolam increased 7-fold after oral administration of midazolam. Concomitant administration of oral midazolam and clarithromycin is contraindicated (see section "Contraindications").

... Simultaneous administration of the drugKlacid® with lovastatin or simvastatin is contraindicated (see section "Contraindications"), since they are largely metabolizedCYP3 A 4, and simultaneous treatment with clarithromycin causes an increase in their plasma concentration, which increases the risk of myopathy and rhabdomyolysis. There are reports of cases of rhabdomyolysis in patients who were simultaneously taking clarithromycin with these statins. If the use of the drugKlacid® cannot be avoided, then taking lovastatin or simvastatin must be suspended for the duration of the drug useKlacid® .

Klacid® with statins. If the simultaneous use of the drugKlacid® and statins are unavoidable, the lowest reported statin dose is recommended. Consideration should be given to prescribing a statin that is not metabolizedCYP3 A eg fluvastatin. It is necessary to monitor the condition of patients in order to identify signs and symptoms of myopathy.

The effect of other drugs on Klacid ® . Drugs that induceCYP3 A (eg, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort) may speed up the metabolism of clarithromycin. This can lead to subtherapeutic levels of clarithromycin and a decrease in its effectiveness. In addition, it may be necessary to monitor the levels of other drugs that induceCYP3 A , which may increase due to the inhibitory effect of clarithromycin onCYP3 A (see also the medical instructions for the respective inhibitorCYP3 A four). Concomitant use of rifabutin and Klacid® led to an increase in rifabutin levels and a decrease in serum clarithromycin concentration with an increased risk of uveitis.

The following drugs affect or are suspected to affect serum clarithromycin concentration. Dose adjustment may be required Klacid ® or considering alternative treatment options

Efavirenz, Nevirapine, Rifampicin, Rifabutin, and Rifapentine

Strong inducers of the cytochrome metabolic systemP 450, such as efavirenz, nevirapine, rifampicin, rifabutin, and rifapentine, can accelerate the metabolism of clarithromycin, thus lowering its plasma concentration while increasing the concentration of its active metabolite (14-OH -clarithromycin). Since the microbiological activity of clarithromycin and 14-OH -clarithromycin in relation to various bacteria is different, then the simultaneous administration of the drugKlacid® and inducers of cytochrome P450 enzymes may interfere with the desired therapeutic effect.

Etravirine : When taking etravirine, exposure to Klacid® decreases, and the concentration of its active metabolite, 14-OH -clarithromycin increases. Since 14-OH -clarithromycin is less active againstMycobacterium avium complex (MAC ), the overall effectiveness of the drug against a given pathogen may change. For this reason, for treatmentMAC alternative treatment options should be considered.

Fluconazole

The simultaneous administration of 200 mg of fluconazole per day and 500 mg of clarithromycin twice a day in 21 healthy volunteers led to an increase in the average equilibrium minimum concentration of clarithromycin (Cmin ) and the area under the curve (AUC ) by 33% and 18%, respectively.

The equilibrium concentrations of the active metabolite 14-OH-clarithromycin did not significantly change with the simultaneous use of fluconazole. Correction of the drug doseKlacid® not required.

Ritonavir

A pharmacokinetic study showed that the simultaneous administration of 200 mg ritonavir every eight hours and the drug Klacid® 500 mg every 12 hours, leads to a marked decrease in clarithromycin metabolism. WhereinCmax clarithromycin increased by 31%,Cmin increased by 182%,AUC increased by 77% with concomitant administration of ritonavir. Almost complete inhibition of the formation of 14-OH -clarithromycin. Due to the wide therapeutic range, dose reductionKlacid® not required in patients with normal renal function. In patients with renal insufficiency, dose adjustment is required: for patients with creatinine clearance (CC) 30-60 ml / min dose of the drugKlacid® must be reduced by 50%. For patients with CC< 30 мл/мин дозу Клацид ® needs to be reduced by 75%. Doses of the drugKlacid® exceeding 1 g / day should not be used with ritonavir. Similar dose adjustments should be made in patients with impaired renal function when ritonavir is used as a pharmacokinetic enhancer in conjunction with other HIV protease inhibitors, including atazanavir and saquinavir (see section “Bilaterally directed drug interactions ").

Influence drug Klacid ® for other drugs

Antiarrhythmic drugs .

In post-marketing practice, cases of ventricular tachycardia of the "pirouette" type (torsades de pointes) while taking clarithromycin and quinidine or disopyramide.

While taking the drugKlacid® with these drugs, it is recommended to carry out ECG monitoring for the timely detection of lengthening of the intervalQT ... During drug therapyKlacid® serum concentrations of these drugs should be monitored. There are also reports of cases of hypoglycemia while taking clarithromycin and disopyramide. While taking the drugKlacid® and disopyramide blood glucose should be monitored.

Oral hypoglycemic agents and insulin .

When used simultaneously with certain hypoglycemic agents such as nateglinide and repaglinide anddrug Klacid® enzyme inhibition may occurCYP3 A clarithromycin, which can cause hypoglycemia. Close monitoring of glucose levels is recommended.

CYP3 A-related interactions .

Simultaneous applicationdrug Klacid® known as an enzyme inhibitorCYP3 A , and the drug primarily metabolizedCYP3 A , can lead to an increase in the concentration of the latter in blood plasma, which, in turn, can enhance or prolong its therapeutic effect and side reactions.

Care should be taken when applyingdrug Klacid® in patients receiving drugs - substratesCYP3 A especially if the latter have a narrow therapeutic range (eg, carbamazepine) and / or are extensively metabolized by this enzyme.

Dose changes and, if possible, close monitoring of serum concentrations of drugs metabolized may be necessary.CYP3 A in patients who simultaneously useKlacid® .

The following drugs or drug groups are known or suspected to be metabolized by the sameCYP3 A isoenzyme: alprazolam, astemizole, carbamazepine, cilostazol, cisapride, cyclosporine, disopyramide, horn alkaloids, lovastatin, methylprednisolone, midazolam, omeprazole, oral anticoagulants (eg, warfarin),atypical antipsychotics (eg, quetiapine), pimozide, quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, terfenadine, triazolam, and vinblastine, but this list is not complete. A similar mechanism of interaction was noted when using phenytoin, theophylline and valproate, which are metabolized by another isoenzyme of the cytochrome P system.450 .

Omeprazole ... There are results of a study on healthy adult volunteers who simultaneously took Klacid® (500 mg every 8 hours) and omeprazole (40 mg daily). When taken simultaneously with the drug Klacid® an increase in the equilibrium plasma concentration of omeprazole was noted (Cmax, AUC0-24 and t1 / 2 increased by 30%, 89% and 34%, respectively). Average value of the indicatorpH in 24 hours in the stomach was 5.2 when taking omeprazole alone and 5.7 when taking omeprazole simultaneously with the drug Klacid® .

Sildenafil, tadalafil and vardenafil .

Each of these phosphodiesterase inhibitors is metabolized, at least in part, with the participationCYP3 A and CYP3 A can be inhibited by concomitant use of clarithromycin. Simultaneous reception of Klacid® and sildenafil, tadalafil, or vardenafil may increase exposure to a phosphodiesterase inhibitor. When using these drugs simultaneously with the drug Klacid® dose reduction of sildenafil, tadalafil, or vardenafil should be considered.

Theophylline, carbamazepine .

The results of clinical studies show that there is a small but statistically significant (p ≤0.05) an increase in the circulating concentration of theophylline or carbamazepine while taking any of these drugs with the drug Klacid® .

Tolterodine mainly metabolized 2D6- isoform of cytochrome P450 (CYP2 D 6). However, in patients withoutCYP2 D 6 metabolism occurs throughCYP3 A ... In this population, oppressionCYP3 A leads to a significant increase in plasma concentrations of tolterodine. For these patients, tolterodine dose reduction may be necessary when used with inhibitorsCYP3 A such as Klacid® .

Triazolobenzodiazepines (eg, alprazolam, midazolam, triazolam).

With the simultaneous appointment of midazolam and clarithromycin tablets (500 mg twice a day), the AUC of midazolam increased 2.7-fold with intravenous midazolam. With intravenous use of midazolam with the drug Klacid® careful monitoring of the patient's condition should be carried out for timely dose adjustment.

With the oromucosal route of administration of midazolam, pre-systemic elimination of the drug may be excluded, which is most likely to lead to an interaction similar to that observed with intravenous administration of midazolam, and not with oral administration.

The same precautions should be followed when using other benzodiazepines that are metabolized by CYP3A, including triazolam and alprazolam. For benzodiazepines, the elimination of which does not depend on CYP3A (temazepam, nitrazepam, lorazepam), the development of a clinically significant interaction with the drug Klacid® is unlikely.

There are post-marketing reports on drug interactions and the development of side effects from the central nervous system (such as drowsiness and confusion) with the simultaneous use of clarithromycin and triazolam. The patient's condition should be monitored, taking into account the possibility of an increase in pharmacological effects from the central nervous system.

Interaction with other medicinal products

Colchicine

Colchicine is a substrate for bothCYP3 A and for the P-glycoprotein carrier protein (Pgp). It is known that Klacid® and other macrolides are inhibitorsCYP3 A and P-glycoprotein. In case of simultaneous use of the drugKlacid® and colchicine, inhibition of P-glycoprotein by clarithromycin and / orCYP3 A may result in increased exposure to colchicine. Simultaneous administration of the drugKlacid® and colchicine is contraindicated (see sections "Contraindications" and "Special instructions").

Digoxin

Digoxin considered to be a carrier protein substrateP-glycoprotein (Pgp ). Clarithromycin is known to inhibitPgp ... With simultaneous useclarithromycin and digoxin, oppressionPgp clarithromycin may increase digoxin exposure.During post-marketing surveillance, an increase in serum digoxin concentrations was reported in patients receiving Klacid® simultaneously with digoxin. Some patients developed signs of digitalis intoxication, including potentially fatal arrhythmias. Serum digoxin concentrations should be carefully monitored in patients receiving digoxin andKlacid® at the same time.

Zidovudine .

Simultaneous oral administration of the drug Klacid® in tablets and zidovudine in adult HIV-infected patients may cause a decrease in the equilibrium concentration of zidovudine. Due to the fact that Klacid® prevents the absorption of concomitantly administered orally zidovudine, this can be largely avoided by observing the 4-hour interval between doses of the drug Klacid® and zidovudine. This interaction does not occur in HIV-infected children receiving Klacid suspension® concomitantly with zidovudine or dideoxyinosine. This interaction is unlikely if clarithromycin is administered by intravenous infusion.

Phenytoin and Valproate .

There have been spontaneous or published reports of inhibitor interactionsCYP3 A , including clarithromycin, with drugs that are not considered to be metabolizedCYP3 A (eg phenytoin and valproate). With the simultaneous appointment of such drugs with the drugKlacid® it is recommended to determine their level in serum. Increases in serum concentrations of these drugs have been reported.

Bilaterally directed drug interactions

Atazanavir

Atazanavir and clarithromycin are substrates and inhibitorsCYP3 A ... There is evidence of a bilaterally directed interaction between these drugs. Simultaneous use of the drug Klacid® (500 mg twice daily) with atazanavir (400 mg once daily) resulted in a doubling of clarithromycin exposure, a decrease in exposure 14-OH -clarithromycin by 70% and an increaseAUC atazanavir by 28%. Due to the wide therapeutic range, dose reductionKlacid® not required in patients with normal renal function. For patients with moderate renal failure (creatinine clearance from 30 to 60 ml / min), the dose of the drugKlacid® should be reduced by 50%. For patients with creatinine clearance less than 30 ml / min, the dose of Klacid® should be reduced by 75% by using the appropriate dosage form.Doses of Klacid ® higher than 1000 mg per day should not be used concomitantly with protease inhibitors.

Calcium channel blockers .

Due to the risk of developingarterial hypotension should be used with cautionKlacid® simultaneously with calcium channel blockers, metabolizedCYP3 A 4 (e.g. verapamil, amlodipine, diltiazem). When interacting, plasma concentrations of both clarithromycin and calcium channel blockers may increase. In patients receiving clarithromycin and verapamil simultaneously, hypotension, bradyarrhythmia, and lactic acidosis were observed.

Itraconazole

Itraconazole and clarithromycin are substrates and inhibitorsCYP3 A leading to bi-directional drug interactions. Clarithromycin may increase plasma levels of itraconazole, whereas itraconazole may increase plasma levels of clarithromycin. When using itraconazole andKlacid® at the same timepatients should be under close medical supervision to identify the manifestations and symptoms of an enhanced or prolonged pharmacological effect.

Saquinavir

Saquinarir and clarithromycin are substrates and inhibitors of CYP3A, and there is evidence of a two-way interaction between these drugs. A study on 12 healthy volunteers showed that the simultaneous administration of the drug Klacid® (500 mg twice daily) and saquinavir (soft gelatin capsules, 1200 mg three times daily) causes an increase in equilibrium AUC and Cmax saquinavir by 177% and 187% compared to taking saquinavir alone. AUC and Cmax clarithromycin increased by about 40% compared with those observed with the drug Clacid® separately. There is no need to adjust the dose if both drugs are used simultaneously for a limited period of time and in the studied doses / dosage forms. The results of drug interaction studies using soft gelatin capsules may not correspond to the effects observed with saquinavir in the form of hard gelatin capsules. Results from drug interaction studies using saquinavir alone may not be consistent with those seen with saquinavir / ritonavir therapy. When saquinavir is used with ritonavir, consideration should be given to the possible effects of ritonavir on clarithromycin (see Drug Interactions).

special instructions

Use of any antimicrobial therapy, in particular clarithromycin, to treatH . pylori -infections can cause selection of resistant microorganisms.

Klacid® should not be administered to pregnant women without a careful assessment of the benefit / risk ratio, especially in the first three months of pregnancy.

Prolonged use, as with other antibiotics, can cause overgrowth of bacteria and fungi that are insensitive to the drug. If superinfection occurs, appropriate therapy should be initiated.

The drug should be used with caution in patients with severe renal impairment.

When taking clarithromycinimpaired liver function has been reported, including elevated liver enzyme levels,hepatocellular and / or cholestatic hepatitis, with or without jaundice. This liver dysfunction can be severe and usually reversible. There have also been cases of fatal liver failure associated with serious comorbidities and / or concomitant use of medications. If symptoms of hepatitis such as anorexia, jaundice, dark urine, itching or tenderness of the abdomen occur, clarithromycin should be stopped immediately.

Pseudomembranous colitis, ranging in severity from mild to life-threatening, has been reported with virtually all antibacterial drugs, including macrolides. When using almost all antibacterial drugs, including Klacid® , the development of diarrhea caused byClostridium difficile (CDAD ) and varying in severity from mild diarrhea to fatal colitis.

Taking antibacterial drugs alters the normal gut flora, resulting in increased growthC. difficile. It is necessary to consider the possibility ofCDAD in all patients who suffer from diarrhea after taking antibiotics. It is necessary to take a careful history, since there have been cases ofCDAD two months after taking antibacterial drugs.

Klacid ® excreted mainly by the liver. Therefore, caution should be exercised when using the drug in patients with impaired liver function, as well as in patients with moderate or severe renal impairment.

Colchicine .

In n ost-marketing reports have reported the toxicity of colchicine while taking clarithromycin and colchicine, especially in elderly patients, some of which have occurred in patients with renal insufficiency. In some of these patients, deaths have been recorded (see section "Drug Interactions"). Simultaneous administration of clarithromycin and colchicine is contraindicated (see section "Contraindications").

Should be used with cautionclarithromycinconcomitantly with triazolobenzodiazepines such as triazolam and midazolam for intravenous or oromucosal administration (see section "Drug interactions").

Prolongation of the QT interval

Prolongation of myocardial repolarization and QT interval, indicating the risk of developing cardiac arrhythmia and bidirectional tachycardia (torsades de pointes ) have been observed with macrolides, including clarithromycin (see section “ Side effects"). Due to the fact that the following situations can lead to an increased risk of ventricular arrhythmias (including bi-directional tachycardia (torsades de pointes )), clarithromycin should be used with caution in the following patient groups:

. Patients with coronary artery disease, severe heart failure, conduction disorders, or clinically significant bradycardia.

. Patients with electrolyte imbalance such as hypomagnesemia. Clarithromycin should not be given to patients with hypokalemia (see section "Contraindications").

. Patients taking other medications in parallel, the action of which is accompanied by a prolongation of the QT interval (see the section "Drug Interactions").

. The simultaneous administration of clarithromycin with astemizole, cisapride, pimozide and terfenadine is contraindicated (see section "Contraindications").

. Clarithromycin should not be used in patients with congenital or established acquired lengthening of the QT interval or a history of ventricular arrhythmias (see section "Contraindications").

Pneumonia .

Due to the developing resistanceStreptococcus pneumoniae to macrolides, it is important to conduct a sensitivity test when prescribingclarithromycin for the treatment of community-acquired pneumonia. In the case of hospital-acquired pneumoniaclarithromycin must be used in combination with other appropriate antibiotics.

Infections of the skin and soft tissues of mild to moderate severity.

The most common causative agents of such infections areStaphylococcus aureus and Streptococcus pyogeneswhich can also be macrolide resistant. Therefore, a sensitivity test should be performed. In cases where the use of beta-lactam antibiotics is not possible (eg due to allergies), other antibiotics such as clindamycin may be the first choice. Currently, macrolides are used only to treat certain types of skin and soft tissue infections, such as infections caused byCorynebacterium minutissimum, acne vulgaris and erysipelas, and in situations where treatment with penicillin is impossible.

In the event that severe acute hypersensitivity reactions are observed, such as anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis and drug skin reactions, accompanied by eosinophilia and systemic manifestations (DRESS ), use of the drugKlacid® should be stopped immediately and appropriate treatment should be started urgently.

Klacid® should be administered with caution in conjunction with inducers of the cytochrome C enzymeYP3 A 4 (see section "Drug interactions").

Consideration should also be given to possible cross-resistance between clarithromycin and other macrolide drugs, such as lincomycin and clindamycin.

HMG-CoA reductase inhibitors (statins) .

Simultaneous use of the drugKlacid® with lovastatin or simvastatin is contraindicated (see section "Contraindications"). Care should be taken when prescribing the drugKlacid® with other statins. There is information about the occurrence of rhabdomyolysis in patients who were simultaneously taking Klacid® and statins. It is necessary to monitor the condition of patients in order to identify signs and symptoms of myopathy. If the concomitant use of clarithromycin and statins is unavoidable, it is recommended to prescribe the minimum registered dose of statin. Consideration should be given to prescribing a statin that is not metabolic dependentCYP3 A , for example, fluvastatin (see section "Drug interactions").

Oral hypoglycemic agents / insulin .

Klacid® and oral hypoglycemic agents (such as sulfonylurea derivatives) and / or insulin, significant hypoglycemia may occur. Close glucose monitoring is recommended.

Oral anticoagulants .

With the simultaneous use of the drugKlacid® with warfarin, there is a risk of serious bleeding and a significant increase in the INR (international normalized ratio) and prothrombin time. With simultaneous useKlacida® and oral anticoagulants should frequently monitor the INR and prothrombin time.

Pregnancy and lactation

Pregnancy

The safety of clarithromycin during pregnancy has not been established. For this reason, the use of the drugKlacid® during pregnancy is not recommended without careful analysis of the balance of benefits and risks.

Lactation period

There is no data on the safety of the drug Klacid ® during breastfeeding. Clarithromycin is excreted in breast milk.

Features of the effect of the drug on the ability to drive a vehicle and potentially dangerous mechanisms

There are no data on the effect of clarithromycin on the ability to drive vehicles and mechanisms. Before driving vehicles and mechanisms, one should take into account the possible occurrence of dizziness, vertigo, confusion and disorientation that may occur when using the drugKlacid® .

Overdose

Symptoms:

Existing reports indicate that gastrointestinal side effects are to be expected when large amounts of clarithromycin are taken orally. There is a history of one patient with a history of bipolar disorder who took 8 grams of clarithromycin, after which he developed a mental change, paranoid behavior, hypokalemia and hypoxemia.

Treatment:

Adverse reactions accompanying an overdose should be treated by immediate elimination of the unabsorbed drug and supportive therapy. As with other macrolides, it is unlikely that hemodialysis or peritoneal dialysis significantly affects serum clarithromycin levels..

Incompatibility

Information is absent.

Release form and packaging

7 tablets are placed in a blister strip packaging.

2 contour packages, together with instructions for medical use in the state and Russian languages, are placed in a cardboard box.

Storage conditions

Store in a dark place at a temperature not exceeding 30 ºС.

Keep out of the reach of children!

Storage period

Do not take the drug after the expiration date printed on the package.

Terms of dispensing from pharmacies

On prescription

Manufacturer

Abbwy S.r.l., Italy

S.R. 148 Pontina K

Marketing Authorization Holder

Abbott Laboratories GmbH, Hannover, Germany

Packer

Abbwy S.r.l., Italy

S.R. 148 Pontina K M 52, SNS - Campoverde di Aprilia (locality Aprilia) - 04011 Aprilia (LT)

The address of the organization that accepts claims from consumers on the quality of products (goods) on the territory of the Republic of Kazakhstan and is responsible for post-registration monitoring of the safety of the medicinal product:

LLP "Abbott Kazakhstan"

050059 Almaty, Republic of Kazakhstan.

dostyk ave. 117/6, Business Center "Khan Tengri-2",

tel .: +7 7272447544, +7 7272447644,

e-mail: [email protected]

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