Aziklar

Aziklar is an anti-microbial drug used systemically. It is part of the group of macrolides.

Indications of the aziklar

It is used for the elimination of infections, provoked by the action of sensitive to clarithromycin microbes:

• infections in the upper part of the respiratory system: in the nasopharynx (such as tonsillitis with pharyngitis), as well as in the paranasal sinuses;
• diseases in the lower part of the respiratory system (such as the atypical form of pneumonia of the primary type, bronchitis and croupous pneumonia in acute form);
• pathology of soft tissues and skin (among them folliculitis with impetigo, as well as furunculosis, erythema Baker and infected wound surfaces);
• infection of the odontogenic type in acute or chronic form;
• diseases of the mycobacterial type (local or common), triggered by the action of Mycobacterium intracellulare or Mycobacterium avium;
• local infections, caused by exposure to mycobacterium, fortified Mycobacterium chelonae, or mycobacterium Kansasi;
• destruction of the Helicobacter pylori bacteria in people with ulcer pathology in the region of the duodenum when suppressing the processes of hydrochloric acid release (the level of activity of the action of clarithromycin on Helicobacter pylori at a neutral pH is higher than in the case of an increased level of acidity).

Release form

Release in tablets, 10 pieces per blister. In a separate package - on the 1st blister plate.

Pharmacodynamics

Clarithromycin is a macrolide antibiotic of the semi-synthetic type. Its antibacterial properties are due to the suppression of the binding of proteins due to synthesis with the ribosomal 50S subunit in substance sensitive microbes.

Often has a bacteriostatic effect, but individual microbes can also be bactericidal. The drug has a powerful specific effect on a relatively large range of anaerobes and aerobes (both gram-positive and gram-negative). Minimal depressive index in clarithromycin is often 2 times lower than the same value for erythromycin.

Clarithromycin in vitro studies demonstrates high efficacy relative to legionella pneumophila and mycoplasma pneumonia. The in vitro and in vivo indices show the potent effect of clarithromycin on drug-specific strains of mycobacteria. In addition, these tests also show that strains of enterobacteria and pseudomonads (as well as gram-negative microorganisms that do not produce lactose) are resistant to clarithromycin.

Clarithromycin, in in vitro tests, as well as in drug practice, actively affects most strains of microbes described below:

• Gram-positive aerobes: Staphylococcus aureus, pneumococcus, streptococcus pyogenes and listeria monocytogenes;
• Gram-negative aerobes: Influenza rod, Haemophilus parainfluenzae, moraxella cataris, gonococcus and Legionella pneumophile;
• other bacteria: mycoplasma pneumonia and chlamydophile pneumonia (TWAR);
• mycobacteria: Hansen's stick, Mycobacterium Kansasi, Mycobacterium chelonae, Mycobacterium fortuitum, and Mycobacterium avium somplex, which includes Mycobacterium intracellulare and Mycobacterium avium.

β-lactamase microbes do not affect the properties of clarithromycin.

Most of methicillin, as well as oxacillin-resistant staphylococcal strains, is resistant to clarithromycin.

Clarithromycin in vitro studies showed an active effect on most of the strains of the bacteria described below, but the safety and drug efficacy of using this drug was not established:

• Gram-positive aerobes: streptococcus agalactia, streptococci types C, F, as well as G, and from the Viridans group;
• Gram-negative aerobes: pertussis and multicid paste;
• other bacteria: Chlamydia trachomatis;
• Gram-positive anaerobes: clostridium perfringence, Peptococcus niger and propionibacterium acne;
• Gram-negative anaerobes: Bacteriodes melaninogenicus;
• spirochaetes: borrelia of Burgdorfer and pale treponema;
• Campylobacterium: Campylobacter effini.

Clarithromycin has bactericidal properties, directed at individual strains of microbes: influenza rod, pneumococcus, streptococcus pyogenes, streptococcus agalactia, moraxella cataris, gonococcus, helicobacter pylori and campylobacter.

The main product of substance disintegration is the element 14-hydroxyclarithromycin, which exhibits microbiological activity. In the majority of microbes this activity is equal to that of the parent substance, or less than 1-2 times (except for the influenza rod, against which the efficiency of the decay product is twice as high). Tests in vitro and also in vivo have shown that the parent substance with its main degradation product has synergistic or additive properties with respect to the hemophilic rod (this depends on the bacterial strain).

Pharmacokinetics

Absorption of clarithromycin from the gastrointestinal tract (mainly through the small intestine) is complete and rapid. The substance remains active when interacting with gastric juice. Reception together with food slows down the absorption, but does not affect its degree of influence. The level of bioavailability is approximately 55%.

It is exposed to hepatic metabolism with the help of the hemoprotein P450 system with the enzyme CYP3A4. There are 3 basic methods (processes of hydroxylation and demethylation, as well as hydrolysis) with the formation of 8 decay products. About 20% of drugs are absorbed after metabolism, during which 14-hydroxyclarithromycin is formed, which is similar to clarithromycin bioactivity.

Clarithromycin, along with its main product of disintegration, is distributed within most biological fluids and tissues. In high concentrations, it accumulates inside the tonsils, nasal mucosa and lung tissue. The indices inside the tissues are higher than inside the bloodstream, because the substance has high intracellular values. The drug easily passes into macrophages with leukocytes, and besides inside the gastric mucosa. The level of clarithromycin inside the gastric tissues and mucosa is higher when combined with omeprazole than during monotherapy.

The peak serum level of clarithromycin is observed after 2-3 hours and is equal to 1-2 mcg / ml in case of using 250 mg 2 times a day. When taking 500 mg of LS twice a day, this figure is 3-4 μg / ml.

About 80% of the drug is synthesized with a plasma protein. Half-life with the use of 250 mg LS (2 times per day) is 2-4 hours, and when you take 500 mg of the drug 2 times a day, it reaches 5 hours. The half-life of active 14-hydroxymetabolite is within 5-6 hours after taking the drug at a rate of 250 mg twice a day.

Approximately 70-80% of the substance is excreted with feces, and about 20-30% - in unchanged form with urine. The latter proportion may increase if the dosage is increased.

If you do not reduce the dose of medication to people with kidney failure, they have a higher plasma index of clarithromycin.

Dosing and administration

Tablets are consumed entirely, washed down with water (they can not be chewed or grinded).

Adolescents from 12 years and adults are required to drink 250 mg of medication at intervals of 12 hours. If a severe form of infection is observed, it is possible to increase the dosage to 500 mg at intervals of 12 hours.

Often, the therapeutic course lasts for 6-14 days. To continue therapy is required at least for 2 days after the disappearance of the main signs of pathology. The duration of the course is determined by the doctor, individually, depending on the course of the illness.

Elimination of odontogenic infectious processes.

Usually a dosage of 250 mg is used with an interval of 12 hours. Take is required in the period of 5 days.

Treatment of infections of the mycobacterial type.

The initial daily dosage is a two-time intake of 500 mg of the drug. If during the 3-4 weeks of therapy there is no improvement in the course of the disease, it is required to increase the dosage of Aziklar to a double intake of 1000 mg LS.

When eliminating infections of disseminated type, provoked by MAK, in people with AIDS, it is required to take pills all the time while microbiological and drug effectiveness of the drug is observed. The drug can be used in combination with other antimycobacterial drugs.

Destruction of Helicobacter pylori bacteria in people with ulcer pathology in the area of the 12-colon (adults):

• triple treatment - the use of 500 mg of clarithromycin (twice daily) in combination with a two-time intake of amoxicillin (1000 mg) and omeprazole (20 mg, once) for 7-10 days;
• triple treatment - the use of clarithromycin (500 mg twice a day), lanoprazole (two-time intake of 30 mg per day) and amoxicillin (twice daily 1000 mg per day) for 10 days;
• double treatment - a triple reception of 500 mg of clarithromycin, and in addition omeprazole (a single dose of 20 or 40 mg of LS per day) during the 14 days;
• double treatment - a three-time use of 500 mg of clarithromycin, as well as a single intake of lanoprazole (60 mg) during 2 weeks. It may be necessary to further inhibit the release of hydrochloric acid in order to reduce ulcerative manifestations.

Clarithromycin can also be used in the following drug regimens:

• combination with tinidazole, as well as omeprazole / lansoprazole;
• simultaneous reception with metronidazole, as well as lanoprazole / omeprazole;
• combination with tetracycline, bismuth subsalicylate, and ranitidine;
• combination with amoxicillin, as well as lansoprazole;
• Combination with ranitidine and citrate bismuth.

When used in people with severe kidney failure (KK values - less than 30 ml / minute), it is required to halve the total daily dosage: take 250 mg once a day or 250 mg twice a day (with a severe form of infection). The duration of therapy in such patients can not be more than 2 weeks.

[1]

Use of the aziklar during pregnancy

There is no information on the safety of taking Aziklar during pregnancy or lactation. Use the drug is only allowed in situations where the likely benefits for women exceed the possible risk of complications in the fetus.

Since clarithromycin is able to penetrate into the mother's milk, it is required to refuse breastfeeding for the duration of treatment.

Contraindications

Among the contraindications:

• the presence of hypersensitivity to clarithromycin or other elements of the drug and other macrolides;
• combination with some drugs: cisapride, terfenadine and astemizole with pimozide (this combination can cause prolongation of the QT-interval, and in addition the appearance of cardiac arrhythmias, among them ventricular tachycardia, ventricular fibrillation and pirouette-type arrhythmia). In addition to carob alkaloids, among which ergotamine with dihydroergotamine (causes the development of ergotoxic effect) and statins that undergo substantial metabolism with the element CYP3A4 (substances lovastatin or simvastatin), since this combination increases the likelihood of myopathy (this also includes rhabdomyolysis);
• concomitant medication with midazolam;
• a history of arrhythmia of the ventricles of the heart (this includes arrhythmia of the pirouette type), as well as prolongation of the QT-interval;
• the presence of hypokalemia (prolongation of the QT-interval);
• liver failure in severe degree and concomitant with her kidney failure;
• combination of clarithromycin (as well as other potent inhibitors of element CYP3A4) with colchicine in people with liver or kidney failure;
• combined use of Aziklar and ranolazine or ticagrelor.

Children aged less than 12 years are required to use the drug in the form of a suspension, since the use of drugs in the form of tablets in this age group has not been studied.

Side effects of the aziklar

Most often with the use of Aziklar develop symptoms such as diarrhea, a disorder of taste buds, abdominal pain and vomiting with nausea. These violations often have a weak expression. Among other side effects:

• invasive and infectious processes: vaginal infection and candidiasis in the oral cavity. In addition, gastroenteritis, erysipelas, pseudomembranous form of colitis, cellulite and erythrasma may develop;
• lymph and hematopoiesis system: development of thrombocyto-, leuko- and neutropenia, as well as agranulocytosis, eosinophilia and thrombocythemia;
• immune reactions: anaphylactic and anaphylactoid manifestations, as well as hypersensitivity;
• metabolic processes: deterioration of appetite, development of anorexia, and in addition the appearance of hypoglycemia in people who take insulin or antidiabetic drugs;
• mental disorders: a sense of disorientation, anxiety, nervousness and confusion, the appearance of insomnia, depression, hallucinations, psychosis and nightmares. In addition, screaming, disorientation and development of mania are possible;
• CNS reactions: loss of consciousness, headaches, feelings of drowsiness and dizziness. Dysgeusia, agesia, dyskinesia and anosmia with parosmia can also develop. Paresthesias, seizures and tremors may occur;
• hearing responses: hearing problems, tinnitus, and reversible hearing loss;
• disorders in the heart: prolongation of QT-interval, increased heart rate, ventricular extrasystole, atrial fibrillation and cardiac arrest;
• disorders in the work of blood vessels: the development of vasodilation and the emergence of hemorrhage;
• reactions of respiratory organs, mediastinum and sternum: occasionally there is a bleeding from the nose, asthma or pulmonary embolism develops;
• manifestations of the gastrointestinal tract: the development of dyspepsia, GERD, stomatitis, esophagitis, procalgia and glossitis with gastritis, and in addition constipation, flatulence, dry mouth mucous, acute pancreatitis and eructation. There may be a change in the shade of the teeth and the tongue;
• disorders in the hepatobiliary system: changes in hepatic elements - an increase in the values of AST, GGT and ALT, as well as bilirubin. In addition, the development of hepatitis, cholestasis (also intrahepatic form), liver failure and parenchymal jaundice;
• subcutaneous tissues and skin: increased sweating, rashes, itching, as well as a rash of the maculopapular type and urticaria. Lyell's syndrome or Stevens-Johnson syndrome, bull type-type dermatitis, acne, an allergy on the skin of a medicamentous type, in which eosinophilia with common symptoms (DRESS), and hemorrhagic vasculitis, can develop;
• reactions of connective tissues and organs of ODA: spasms in muscles, myopathy with myalgia, rhabdomyolysis and rigidity of skeletal muscles;
• the reaction of the organs of urination and kidneys: the development of kidney failure or tubulointerstitial nephritis, and in addition an increase in urea or creatinine;
• systemic disorders: a state of fever, a feeling of fatigue and malaise, pain in the sternum, as well as chills and asthenia;
• the results of laboratory tests: an increase in LDH or AFP, a change in the proportions of albumin / globulin, prolongation of PTV, increased levels of INR, serum creatinine, and AMK. The shade of urine may change.

There is information about the development of edema Quincke and arthralgia.

Occasionally, there was reported the occurrence of uveitis - mainly in people taking rifabutin in combination with Aziklar. Reactions were often curable.

There is also information about the occurrence of colchicine toxicity (in some cases even fatal) due to the combination of clarithromycin and colchicine. In particular, this applies to the elderly, as well as when taken against a background of kidney failure.

Patients with immunodeficiency disorder.

In people with AIDS or other immunodeficiency disorders taking the medicine in large doses for a longer period than is required to eliminate mycobacterial type infections, it is not always possible to distinguish side effects caused by the use of drugs, with manifestations of the underlying pathology and accompanying disorders.

In Aziklar 500, there is a dye tartrazine (element E 102) capable of provoking allergy manifestations.

Overdose

As a result of an overdose of the drug, manifestations may develop on the part of the digestive tract, and in addition hypokalemia, headaches and hypoxemia. One patient who had a history of bipolar psychosis, with the use of 8 grams of clarithromycin, began to change the mental state, and also developed hypoxemia with hypokalemia and paranoia.

When developing an overdose, it is necessary to cancel the use of drugs.

The medicine does not have a specific antidote. For treatment, gastric lavage and the use of activated charcoal are used. In addition, the required symptomatic therapy is conducted to support the work of life-critical systems and organs. The likelihood that the procedures of peritoneal dialysis and hemodialysis can affect the serum indices of clarithromycin is quite low. Therefore, it is not recommended to conduct them.

Interactions with other drugs

Aziklar increases the indices in the body of drugs that are metabolized by the hemoprotein system P450. Among such drugs - alprazolam, rifabutin and terfenadine with cisapride, and besides this, bromocriptine with astemizole, pimozide with valproate, warfarin and ergot alkaloids with hexobarbital and midazolam. In addition, also triazolam and phenytoin, cyclosporine with digoxin, sildenafil with quinidine, disopramide, methylprednisolone and vinblastine with theophylline, tacrolimus and zidovudine. If necessary, such a combination requires careful monitoring of their level in the blood, and also in time to adjust the size of the dose.

When combined with the substance ergotamine or dihydroergotamine, the occurrence of ischemia of different tissues (among them tissue in the extremities and in the central nervous system) and vasospasm may occur.

Combined use with simvastatin, as well as lovastatin and atorvastatin may cause rhabdomyolysis.

Combination with colchicine results in an increase in the toxic properties of this drug.

[2], [3]

Storage conditions

The medicine must be kept in a place inaccessible to young children. Temperature conditions - no more than 30 ° С.

Shelf life

Aziklar can be used in the 3 years since the release of the drug.