Azitrox (Azithromycin)

Pharmacotherapeutic group: antibiotic azalide

ATX Code: [J01FA10]

Azithromycin is a broad-spectrum bacteriostatic antibiotic from the group of azrolide macrolides. It has a wide range of antimicrobial effects. The mechanism of action of azithromycin is associated with the suppression of protein synthesis of microbial cells. By binding to the 50S subunit of the ribosome, it inhibits the peptide translocase at the translation stage and inhibits protein synthesis, slowing the growth and reproduction of bacteria. In high concentrations it has a bactericidal effect.

It has activity against a number of gram-positive, gram-negative, anaerobic, intracellular and other microorganisms.

Sensitive microorganisms: aerobic gram-positive microorganisms - Staphylococcus aureus (methicillin-sensitive strains), Streptococcus pneumoniae (penicillin-sensitive strains), Streptococcus pyogenes, Streptococcus spp. (group C, F and G); aerobic gram-negative microorganisms - Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis, Pasteurella multocida, Neisseria gonorrhoeae; anaerobic microorganisms - Clostridium perfringens, Fusobacterium spp., Prevotella spp., Porphyriomonas spp .; other microorganisms - Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.

 Microorganisms with acquired resistance to azithromycin: aerobic gram-positive microorganisms - Streptococcus pneumoniae (penicillin-resistant strains and strains with moderate sensitivity to penicillin).

Microorganisms with natural resistance to azithromycin: aerobic gram-positive microorganisms - Enterococcus faecalis, Staphylococcus aureus (methicillin-resistant strains), Staphylococcus epidermidis (methicillin-resistant strains); anaerobic microorganisms - Bacteroides fragilis.

Cases of cross-resistance in Streptococcus pneumoniae, Streptococcus pyogenes (beta-hemolytic Streptococcus group A), Enterococcus faecalis and Staphylococcus aureus (including methicillin-resistant strains) to erythromycin, other macrolides, lincosamides and azithromycin are described.

The scale of sensitivity of microorganisms to azithromycin (Minimum inhibitory concentration (MIC), mg / l)

Pharmacokinetics 

After oral administration, bioavailability is 37%, the maximum concentration in blood plasma (Cmax) is created after 2-3 hours, the volume of distribution is 31.1 l / kg. Binding to blood proteins is inversely proportional to the concentration in the blood and is 7-50%. 

Penetrates through cell membranes (effective in infections caused by intracellular pathogens). It is transported by phagocytes, polymorphonuclear leukocytes and macrophages to the site of infection, where it is released in the presence of bacteria. 

It easily passes through the histohematological barriers and enters the tissues. The concentration in tissues and cells is 50 times higher than in blood plasma, and in the focus of infection - by 24-34% more than in healthy tissues.

It has a long half-life of 2-4 days. The half-life of tissues is much longer. The therapeutic concentration of azithromycin lasts up to 5-7 days after the last dose. Azithromycin is excreted mainly unchanged - 50% of the intestine, 6% of the kidneys. In the liver, demethylates, losing activity.

Infectious and inflammatory diseases caused by microorganisms sensitive to azithromycin, including:

• upper respiratory tract and ENT organs, including pharyngitis / tonsillitis, sinusitis, otitis media;
• lower respiratory tract, including acute bronchitis, exacerbation of chronic bronchitis and community-acquired pneumonia;
• urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis);
• infections of the skin and soft tissues (acne vulgaris (acne) of moderate severity, erysipelas, impetigo, secondarily infected dermatoses);
• Lyme disease - the initial stage (erythema migrans - erythema migrans).

Most of the reported adverse reactions are reversible after the end of the course of treatment or discontinuation of the drug.

Classification of the frequency of side effects (WHO): very often (with a frequency of more than 1/10), often (with a frequency of at least 1/100, but less than 1/10), infrequently (with a frequency of at least 1/1000, but less than 1 / 100), rarely (with a frequency of at least 1/10000, but less than 1/1000), very rarely (with a frequency of less than 1/10000), including individual messages.

From the circulatory and lymphatic systems: often - lymphocytopenia, eosinophilia; infrequently - leukopenia, neutropenia; very rarely - thrombocytopenia, hemolytic anemia.

From the central nervous system: often - dizziness, headache, paresthesia, impaired taste perception, anorexia; infrequently - anxiety, nervousness, hyposthesia, insomnia, drowsiness; rarely - agitation, delirium, hallucinations; very rarely - fainting, convulsions, psychomotor hyperactivity, aggression, anosmia, loss of taste, perversion of smell, aggravation of myasthenia gravis.

From the sensory organs: infrequently - hearing impairment, vertigo, visual impairment; unknown frequency - hearing impairment, including deafness and / or tinnitus.

From the respiratory system and ENT organs: infrequently - shortness of breath, nosebleeds.

 From the cardiovascular system: infrequently - a feeling of palpitations;

“Flushing” of blood to the face; very rarely - a decrease in blood pressure, arrhythmia, ventricular tachycardia, an increase in the QT interval, pirouette type arrhythmia.

Infectious diseases: infrequently - rhinitis, respiratory diseases, pharyngitis, pneumonia, candidiasis, including the oral mucosa and genitals, gastroenteritis.

From the digestive system: very often - nausea, diarrhea, abdominal pain, flatulence (bloating), often - vomiting; infrequently - dryness of the oral mucosa, ulcers of the oral mucosa, increased secretion of the salivary glands, belching, gastritis, dnsphagia, constipation; very rarely - discoloration of the tongue, pseudomembranous colitis, pancreatitis.

On the part of the liver and biliary tract: infrequently - hepatitis, hyperbilirubinemia, increased activity of “liver” transaminases; very rarely - cholestatic jaundice, liver failure (in rare cases with a fatal outcome, mainly due to impaired liver function), fulminant hepatitis, liver necrosis.

Allergic reactions: often - itching, rash; infrequently - Stevens-Johnson syndrome, photosensitivity, urticaria; very rarely - anaphylactic reactions (including angioedema) in rare cases with a fatal outcome, toxic epidermal necrolysis, erythema multiforme.

On the part of the skin and subcutaneous tissues: dermatitis, dry skin, sweating.

From the musculoskeletal system: often - arthralgia; infrequently - osteoarthritis, myalgia, back pain, neck pain.

From the urinary system: infrequently - increased residual urea nitrogen and plasma creatinine concentrations, dysuria, pain in the kidneys; very rarely - interstitial nephritis, acute renal failure.

From the genitals and mammary gland: infrequently - metrorrhagia, impaired testicular function.

Other: often - weakness; infrequently - chest pain, peripheral edema, asthenia (malaise, feeling tired), fever, swelling of the face.

Laboratory data: often-an increase in the number of basophils, monocytes, neutrophils, a decrease in the concentration of bicarbonates in blood plasma; infrequently - an increase in alkaline phosphatase activity, an increase in chlorine content, an increase in glucose concentration, an increase in the concentration of bicarbonates in blood plasma, an increase in the number of platelets, an increase in hematocrit, a change in the content of sodium and potassium in blood plasma.

Antacids (aluminum and magnesium-containing) do not affect the bioavailability of azithromycin, but reduce its Cmax by 30%, so the drug should be taken at least one hour before or two hours after taking these drugs.

Azithromycin does not affect the concentration of carbamazepine, cimetidine, didanosine, efavirenz, fluconazole, indinavir, midazolam, theophylline, triazolam, trimethoprim / sulfamethoxazole, cetirizine, sildenafil, atorvastatin, rifabutinone and methyl rifabutinone.

With the simultaneous use of azithromycin and cyclosporine, dose adjustment of cyclosporin is necessary. With the simultaneous administration of digoxin and azithromycin, it is necessary to control the concentration of digoxin in the blood, since many macrolides increase the absorption of digoxin in the intestine, thereby increasing its Cmax.

With the simultaneous use of ergotamine and dihydroergotamine derivatives, an increase in the toxic effect (vasospasm, dysesthesia) of the latter is possible.

If necessary, simultaneous administration with indirect anticoagulants (warfarin and other coumarin type anticoagulants), it is recommended to control prothrombin time.

It was found that the simultaneous administration of terfenadine or cisapride and macrolide antibiotics causes arrhythmia and lengthening of the QT interval. Based on this, the above complications cannot be excluded with the combined use of azithromycin and terfenadine.

With the joint administration of azithromycin and zidovudine, azithromycin has a slight effect on the pharmacokinetics, including excretion by the kidneys, zidovudine or its glucuronide metabolite; azithromycin weakly interacts with cytochrome P450 isoenzymes; it has not been revealed that azithromycin is involved in pharmacological interactions similar to erythromycin and other macrolides; azithromycin is not an inducer and inhibitor of cytochrome P450 isoenzymes.

With the simultaneous administration of azithromycin and rifabutin in rare cases, the development of neutropenia is possible, the mechanism of development of which, as well as the presence of a causal relationship with the drug has not been established.

The simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times a day) causes an increase in the equilibrium concentration of azithromycin in the blood plasma, no clinically significant side effects were observed and dose adjustment of azithromycin when used simultaneously with nelfinavir is not required.

Set individually, taking into account the nosological form, the severity of the disease and the sensitivity of the pathogen.

Adults inside - 0.25-1 g 1 time / day; children - 5-10 mg / kg 1 time / day. Duration of administration is 2-5 days.

When prescribing to patients with diabetes mellitus, as well as with a low-calorie diet, it must be borne in mind that the suspension contains sucrose (3.7 g / 5 ml or 0.3 XE / 5 ml).

If you miss one dose of the drug, the missed dose should be taken as soon as possible, and the next dose should be taken at intervals of 24 hours. It is necessary to observe the regimen recommended in the instructions and the duration of the drug.

Azithromycin is contraindicated in patients with severely impaired liver function.

Patients with impaired liver function of mild to moderate severity should be prescribed with caution because of the possibility of developing fulminant hepatitis and severe liver failure. If there are symptoms of impaired liver function (rapidly growing asthenia, jaundice, dark urine, a tendency to bleeding, hepatic encephalopathy), azithromycin therapy should be discontinued and a study of the functional state of the liver should be carried out.

In case of impaired renal function: in patients with a glomerular filtration rate of 10-80 ml / min, dose adjustment is not required, therapy with Azitrox ^® should be carried out with caution under the control of the state of renal function.

There is no data on the possible interaction between azithromycin and derivatives of ergotamine and dihydroergotamine, but due to the development of ergotism while taking macrolides with derivatives of ergotamine and dihydroergotamine, this combination is contraindicated.

With prolonged use of azithromycin, pseudomembranous colitis caused by Clostridium difficile may develop, both in the form of mild diarrhea and severe colitis. The use of drugs inhibiting intestinal motility is contraindicated. With the development of diarrhea while taking azithromycin, and also 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded.

With a syndrome of delayed repolarization of the ventricles - a syndrome of lengthening the QT interval - with macrolides, including azithromycin, the risk of developing arrhythmia increases. 

Caution when prescribing azithromycin should be observed in patients with a prolonged QT interval receiving therapy with antiarrhythmic agents of classes IA, III, cisapride, in the presence of hypokalemia or hypomagnesemia, clinically significant bradycardia, arrhythmia, or severe heart failure.

The use of azithromycin can provoke the development of myasthenic syndrome or cause an exacerbation of myasthenia gravis.

As with other antibacterial drugs, patients with azithromycin should be regularly examined for the presence of immune microorganisms and signs of superinfection, including fungal infections.

Influence on the ability to drive vehicles and mechanisms.

Powder for oral suspension