Aziclar

Aziklar is an antimicrobial drug used systemically. It belongs to the macrolide group.

Indications Aziclara

It is used to eliminate infections caused by the action of microbes sensitive to clarithromycin:

• infections in the upper respiratory tract: in the nasopharynx (such as tonsillitis with pharyngitis), as well as in the paranasal sinuses;
• diseases of the lower respiratory tract (such as atypical primary pneumonia, bronchitis and acute lobar pneumonia);
• pathologies of soft tissues and skin (including folliculitis with impetigo, as well as furunculosis, Baker's erythema and infected wound surfaces);
• odontogenic infections in acute or chronic form;
• mycobacterial diseases (local or widespread), caused by the action of Mycobacterium intracellulare or Mycobacterium avium;
• local infections caused by Mycobacterium fortuitum, Mycobacterium chelonae or Mycobacterium kansashi;
• destruction of Helicobacter pylori bacteria in people with ulcerative pathology in the duodenum by suppressing the processes of secretion of hydrochloric acid (the level of activity of clarithromycin on Helicobacter pylori at a neutral pH is higher than in the case of increased acidity).

Release form

Released in tablets, 10 pieces in a blister. In a separate package - 1 blister plate.

Pharmacodynamics

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

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

Clarithromycin demonstrates high efficacy against Legionella pneumophila and Mycoplasma pneumoniae in in vitro studies. In vitro and in vivo data show clarithromycin has a powerful effect on drug-relevant mycobacterial strains. 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 vitro tests and in medicinal practice, actively affects most strains of the microbes described below:

• gram-positive aerobes: Staphylococcus aureus, pneumococcus, Streptococcus pyogenes and Listeria monocytogenes;
• Gram-negative aerobes: influenza bacillus, Haemophilus parainfluenzae, Moraxella catarrhalis, gonococcus and Legionella pneumophila;
• other bacteria: Mycoplasma pneumoniae and Chlamydophila pneumoniae (TWAR);
• Mycobacteria: Hansen's bacillus, Mycobacterium kansashi, Mycobacterium chelonae, Mycobacterium fortuitum, and Mycobacterium avium complex, which includes Mycobacterium intracellulare and Mycobacterium avium.

Microbial Β-lactamases do not affect the properties of clarithromycin.

Most methicillin- and oxacillin-resistant staphylococcal strains are resistant to clarithromycin.

Clarithromycin has been shown to be active against most strains of the bacteria described below in vitro studies, but the safety and medicinal efficacy of this drug have not been established:

• gram-positive aerobes: Streptococcus agalactiae, streptococci types C, F, and G, and from the Viridans group;
• gram-negative aerobes: whooping cough bacillus and Pasteurella multocida;
• other bacteria: Chlamydia trachomatis;
• Gram-positive anaerobes: Clostridium perfringens, Peptococcus niger and Propionibacterium acnes;
• gram-negative anaerobes: Bacteriodes melaninogenicus;
• spirochetes: Borrelia burgdorferi and Treponema pallidum;
• Campylobacter: Campylobacter jeuni.

Clarithromycin has bactericidal properties against certain strains of microbes: influenza bacillus, pneumococcus, Streptococcus pyogenes, Streptococcus agalactiae, Moraxella catarrhalis, gonococcus, Helicobacter pylori and Campylobacter.

The main decay product of the substance is the element 14-hydroxyclarithromycin, which exhibits microbiological activity. For most microbes, this activity is equal to similar indicators of the parent substance, or is 1-2 times weaker (the only exception is the influenza bacillus, against which the efficiency of the decay product is twice as high). In vitro and in vivo tests have shown that the parent substance with its main decay product have synergistic or additive properties relative to the hemophilic bacillus (this depends on the bacterial strain).

Pharmacokinetics

Clarithromycin is absorbed from the gastrointestinal tract (mainly through the small intestine) completely and quickly. The substance remains active when interacting with gastric juice. Taking it with food slightly slows down absorption, but does not affect its degree. The bioavailability level is approximately 55%.

It undergoes hepatic metabolism using the P450 hemoprotein system with the CYP3A4 enzyme. This occurs by 3 main methods (hydroxylation and demethylation processes, as well as hydrolysis) with the formation of 8 decay products. About 20% of the drug after absorption undergoes metabolism, during which 14-hydroxyclarithromycin is formed, which has bioactivity similar to clarithromycin.

Clarithromycin, together with its main decay product, is distributed within most biological fluids and tissues. In high concentrations, it accumulates within the tonsils, nasal mucosa and pulmonary tissues. The indices within the tissues are higher than within the bloodstream, because the substance has high intracellular values. The drug easily passes into macrophages with leukocytes, and also into the gastric mucosa. The level of clarithromycin within the gastric tissues and mucosa is higher in the case of its combination with omeprazole than during monotherapy.

Peak serum levels of clarithromycin are observed after 2-3 hours and are equal to 1-2 mcg/ml when using 250 mg 2 times a day. When taking 500 mg of the drug 2 times a day, this indicator is 3-4 mcg/ml.

About 80% of the drug is synthesized with plasma protein. The half-life of 250 mg of the drug (2 times a day) is 2-4 hours, and when taking 500 mg of the drug 2 times a day, it reaches 5 hours. The half-life of the active 14-hydroxy metabolite is within 5-6 hours after taking the drug in a dose of 250 mg twice a day.

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

If the dose of the drug is not reduced in people with renal failure, their plasma levels of clarithromycin increase.

Dosing and administration

The tablets are taken whole with water (they should not be chewed or crushed).

Teenagers aged 12 and over and adults are required to take 250 mg of the medicine at 12-hour intervals. If a severe form of infection is observed, the dosage may be increased to 500 mg at 12-hour intervals.

Often the therapeutic course lasts for 6-14 days. The therapy must be continued for at least 2 more days after the disappearance of the main signs of the pathology. The duration of the course is prescribed by the doctor, individually, depending on the course of the disease.

Elimination of odontogenic infectious processes.

The usual dosage is 250 mg, taken every 12 hours. It must be taken over a period of 5 days.

Treatment of mycobacterial infections.

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

When eliminating disseminated infections caused by MAC in people with AIDS, it is necessary to take tablets for the entire period while the microbiological and medicinal 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 ulcerative pathology in the duodenum (in adults):

• triple therapy – taking 500 mg of clarithromycin (twice a day) in combination with twice daily amoxicillin (1000 mg) and omeprazole (20 mg, once) for a period of 7-10 days;
• triple therapy – use of clarithromycin (500 mg twice daily), lanoprazole (30 mg twice daily) and amoxicillin (1000 mg twice daily) for 10 days;
• dual treatment – three times a day administration of 500 mg of clarithromycin, and also omeprazole (single dose of 20 or 40 mg of the drug per day) for 14 days;
• Dual therapy – clarithromycin 500 mg three times a day, plus lanoprazole 60 mg once a day for 2 weeks. Subsequent suppression of hydrochloric acid secretion may be necessary to reduce ulcerative manifestations.

Clarithromycin may also be used in the following dosage regimens:

• combination with tinidazole, as well as omeprazole/lansoprazole;
• concomitant administration 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 bismuth citrate.

When used in people with severe renal failure (CR indicators are less than 30 ml/minute), the total daily dosage must be halved: take 250 mg once a day or 250 mg twice a day (in severe infections). The duration of therapy in such patients cannot exceed 2 weeks.

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Use Aziclara during pregnancy

There is no information on the safety of taking Aziklar during pregnancy or lactation. The drug is allowed to be used only in situations where the probable benefit to the woman outweighs the possible risk of complications for the fetus.

Since clarithromycin can penetrate into breast milk, breastfeeding should be discontinued during treatment.

Contraindications

Among the contraindications:

• the presence of hypersensitivity to clarithromycin or other components of the drug and other macrolides;
• combination with certain medications: cisapride, terfenadine and astemizole with pimozide (this combination can cause prolongation of the QT interval, as well as the occurrence of cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation and pirouette-type arrhythmia). In addition, with carob alkaloids, including ergotamine with dihydroergotamine (causes the development of ergotoxic effects) and statins, which are significantly metabolized by the CYP3A4 element (substances lovastatin or simvastatin), since this combination increases the likelihood of myopathy (this also includes rhabdomyolysis);
• combined administration of the drug with midazolam;
• a history of ventricular arrhythmia (including torsades de pointes) and prolongation of the QT interval;
• the presence of hypokalemia (prolongation of the QT interval);
• severe liver failure and concomitant renal failure;
• combination of clarithromycin (as well as other strong inhibitors of the CYP3A4 element) with the substance colchicine in people with liver or kidney failure;
• combined use of Aziclar and ranolazine or ticagrelor.

Children under 12 years of age are required to take the medicine in the form of a suspension, since the use of the medicine in tablet form in this age category has not been studied.

Side effects Aziclara

The most common symptoms that develop with Aziklar include diarrhea, taste bud disorders, abdominal pain, and vomiting with nausea. These disorders are often mild. Other side effects include:

• invasive and infectious processes: vaginal infection and oral candidiasis. In addition, gastroenteritis, erysipelas, pseudomembranous colitis, cellulitis and erythrasma may develop;
• lymph and hematopoietic 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: loss of appetite, development of anorexia, and also the appearance of hypoglycemia in people who take insulin or antidiabetic drugs;
• mental disorders: feelings of disorientation, anxiety, nervousness and confusion, insomnia, depression, hallucinations, psychosis and nightmares. In addition, screaming, disorientation and the development of mania are possible;
• CNS reactions: loss of consciousness, headaches, drowsiness and dizziness. Dysgeusia, ageusia, dyskinesia and anosmia with parosmia may also develop. Paresthesia, convulsions and tremors may occur;
• reactions of the auditory organs: hearing problems, tinnitus, as well as reversible hearing loss;
• disorders of the heart: prolongation of the QT interval, increased heart rate, ventricular extrasystole, atrial fibrillation and cardiac arrest;
• vascular dysfunction: development of vasodilation and occurrence of hemorrhage;
• reactions of the respiratory organs, mediastinum and sternum: occasionally nosebleeds occur, asthma or pulmonary embolism develops;
• Gastrointestinal manifestations: development of dyspepsia, GERD, stomatitis, esophagitis, proctalgia and glossitis with gastritis, as well as constipation, flatulence, dry oral mucosa, acute pancreatitis and belching. Changes in the shade of teeth and tongue may be observed;
• disorders in the hepatobiliary system: changes in liver element indices – increased AST, GGT and ALT values, as well as bilirubin. In addition, the development of hepatitis, cholestasis (also its intrahepatic form), liver failure and parenchymatous jaundice;
• Subcutaneous tissues and skin: increased sweating, rashes, itching, as well as maculopapular rash and urticaria. Lyell's syndrome or Stevens-Johnson syndrome, bullous dermatitis, acne, drug-induced skin allergy with eosinophilia with general symptoms (DRESS), and hemorrhagic vasculitis may develop;
• reactions of connective tissues and musculoskeletal organs: muscle spasms, myopathy with myalgia, rhabdomyolysis and rigidity of skeletal muscles;
• reactions of the urinary organs and kidneys: development of renal failure or tubulointerstitial nephritis, as well as an increase in urea or creatinine levels;
• systemic disorders: fever, feeling of fatigue and malaise, chest pain, as well as chills and asthenia;
• laboratory test results: increased LDH or ALP levels, changes in albumin/globulin ratios, prolongation of PT, increased INR, serum creatinine, and AMC. Urine color may change.

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

Uveitis has been reported rarely, mostly in people taking the drug rifabutin in combination with Aziklar. The reactions were often treatable.

There is also information about the occurrence of colchicine toxicity (in some cases even fatal) due to the combination of clarithromycin and colchicine. This is especially true for the elderly, as well as when taken against the background of renal failure.

Patients with immune disorders.

In people with AIDS or other immune disorders who have taken the drug in high doses for a longer period than is required to eliminate mycobacterial infections, it is not always possible to distinguish between the side effects caused by the use of the drug and the manifestations of the underlying pathology and associated disorders.

Aziklar 500 contains the dye tartrazine (element E 102), which can provoke allergic reactions.

Overdose

Overdose of the drug may result in gastrointestinal manifestations, as well as hypokalemia, headaches, and hypoxemia. One patient with a history of bipolar psychosis developed mental changes, hypoxemia with hypokalemia, and paranoia when taking 8 g of clarithromycin.

If an overdose occurs, it is necessary to stop using the drug.

The drug has no specific antidote. Gastric lavage and activated carbon are used for treatment. In addition, the required symptomatic therapy is carried out to support the work of vital systems and organs. The likelihood that peritoneal dialysis and hemodialysis procedures will be able to affect serum clarithromycin levels is quite low. Therefore, they are not recommended.

Interactions with other drugs

Aziklar increases the levels of drugs metabolized by the P450 hemoprotein system in the body. Such drugs include alprazolam, rifabutin, and terfenadine with cisapride, as well as bromocriptine with astemizole, pimozide with valproates, warfarin, and ergot alkaloids with hexobarbital and midazolam. In addition, triazolam and phenytoin, cyclosporine with digoxin, sildenafil with quinidine, disopramide, methylprednisolone, and vinblastine with theophylline, tacrolimus, and zidovudine. If such a combination is necessary, their blood levels should be closely monitored and the dose adjusted in a timely manner.

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

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

Combination with colchicine leads to increased toxic properties of this drug.

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Storage conditions

The medicine should be kept in a place inaccessible to small children. Temperature conditions – no more than 30°C.

Shelf life

Aziklar can be used for a period of 3 years from the date of release of the drug.