Pharmacological action
Pharmacotherapeutic group: antibiotic-azalide
ATX Code: [J01FA10]
Pharmacological properties
Azithromycin is a broad-spectrum bacteriostatic antibiotic from the group of macrolides-azalides. It has a wide spectrum of antimicrobial action. The mechanism of action of azithromycin is associated with the suppression of microbial cell protein synthesis. Binding to the 50S subunit of the ribosome, it inhibits peptidtranslase at the translation stage and suppresses protein synthesis, slowing down 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.
Susceptible organisms: aerobic gram – positive microorganisms Staphylococcus aureus (methicillinsusceptible strains), Streptococcus pneumoniae (penicillinsusceptible strains), Streptococcus pyogenes, Streptococcus spp. (groups 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 micro – organisms Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.
Microorganisms with acquired resistance to azithromycin: aerobic gram – positive microorganisms Streptococcus pneumoniae (penicillinresistant strains and strains with average 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.
Scale of sensitivity of microorganisms to azithromycin (Minimum inhibitory concentration (MIC), mg / l)
Micro-organisms |
MIC, mg/l |
|
Sensitive |
Resistant |
|
Staphylococcus spp. |
not more than 1 |
more than 2 |
Streptococcus A, B, C, G |
not more than 0.25 |
more than 0.5 |
Streptococcus pneumoniae |
not more than 0.25 |
more than 0.5 |
Haemophilus influenzae |
not more than 0.12 |
more than 4 |
Moraxella catarrhalis |
not more than 0.5 |
more than 0.5 |
Neisseria gonorrhoeae |
not more than 0.25 |
more than 0.5 |
Pharmacokinetics.
After oral use, the bioavailability is 37%, the maximum concentration in blood plasma (Cmax) is created in 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 cell membranes (effective for 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 histohematic 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-24-34% higher than in healthy tissues.
It has a long half-life of 2-4 days. The tissue half-life is significantly longer. The therapeutic concentration of azithromycin is maintained up to 5-7 days after the last dose. Azithromycin is mainly excreted unchanged-50% by the intestines,6% by the kidneys. In the liver, it is demethylated, losing its activity.
In patients with severe renal insufficiency (creatinine clearance < 10 ml/min), the half-life of azithromycin is increased by 33%.
Indications
Infectious and inflammatory diseases caused by microorganisms sensitive to azithromycin, including:
- the upper respiratory tract and ENT-organs, including pharyngitis/tonsillitis, sinusitis, otitis media;
- lower respiratory tract infections, including acute bronchitis, exacerbation of chronic bronchitis and community-acquired pneumonia;
- urinary tract infection caused by Chlamydia trachomatis (urethritis, cervicitis);
- infections of skin and soft tissue (acne vulgaris (acne) of moderate severity, erysipelas, impetigo, secondarily infected dermatoses);
- Lyme disease – the initial stage (erythema migrans rash – erythema migrans).
Use during pregnancy and lactation
Animal studies have not shown any harmful effects on the fetus, and data on the efficacy and safety of azithromycin in pregnant women are limited. Azithromycin is used during pregnancy only if the intended benefit to the mother outweighs the possible risk to the fetus. If it is necessary to prescribe the drug during lactation, stop breastfeeding.
Contraindications
- Hypersensitivity to azithromycin, other macrolides (including erythromycin, ketolides) or other components of the drug;
- severe hepatic impairment (no data on efficacy and safety);
- sucrose/isomaltase deficiency,
- fructose intolerance, glucose-galactose malabsorption;
- children under 6 months of age;
- breastfeeding;
- simultaneous use of ergotamine and dihydroergotamine.
Use caution in patients with mild to moderate hepatic impairment; end-stage renal failure with a glomerular filtration rate of less than 10 ml / min; in patients with proarrhythmogenic factors (especially in elderly patients): patients with congenital or acquired prolongation of the QT interval; co-use with antiarrhythmic agents of classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin); with violations of the water-electrolyte balance, especially in the presence of in case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, arrhythmia or severe heart failure; concomitant use of terfenadine, warfarin, digoxin, cyclosporine, pregnancy, myasthenia gravis, diabetes mellitus.
Side effects
Most of the reported adverse reactions are reversible after the end of treatment or discontinuation of the drug.
WHO classification of frequency of side effects: very common (with a frequency of more than 1/10), common (with a frequency of at least 1/100, but less than 1/10), infrequent (with a frequency of at least 1/1000, but less than 1/100), rare (with a frequency of at least 1/10000, but less than 1/1000), very rare (with a frequency of less than 1/10000), including individual reports.
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 perception of taste sensations, anorexia; infrequently-anxiety, nervousness, hyposthesia, insomnia, drowsiness; rarely-agitation, delirium, hallucinations; very rarely-fainting, convulsions, psychomotor hyperactivity, aggression, anosmia, loss of taste sensations, perversion of smell, exacerbation of myasthenia gravis.
Sensory disorders: infrequently – hearing disorder, 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-palpitation sensation;
“flushes” of blood to the face; very rarely-decreased blood pressure, arrhythmia, ventricular tachycardia, increased QT interval, arrhythmia of the “pirouette” type.
Infectious diseases: infrequently-rhinitis, respiratory diseases, pharyngitis, pneumonia, candidiasis, including oral and genital mucosa, 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 salivary gland secretion, belching, gastritis, dysphagia, constipation; very rarely – discoloration of the tongue, pseudomembranous colitis, pancreatitis.
From the liver and biliary tract: infrequently-hepatitis, hyperbilirubinemia, increased activity of “hepatic” transaminases; very rarely-cholestatic jaundice, liver failure (in rare cases with a fatal outcome, mainly against the background of impaired liver function), fulminant hepatitis, liver necrosis.
Allergic reactions: often-pruritus, rash; infrequently-Stevens-Johnson syndrome, photosensitization, urticaria; very rarely – anaphylactic reactions (including angioedema) in rare cases with fatal outcome, toxic epidermal necrolysis, erythema multiforme.
Skin and subcutaneous tissue disorders: 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 concentration, dysuria, pain in the kidney area; very rarely-interstitial nephritis, acute renal failure.
From the genitals and breast: infrequently-metrorrhagia, testicular dysfunction.
Others: often-weakness; infrequently-chest pain, peripheral edema, asthenia (malaise, feeling tired), fever, facial edema.
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 the activity of alkaline phosphatase, an increase in the content of chlorine, an increase in the concentration of glucose, 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.
Any side effect should be reported to the attending physician.
Interaction
Antacids (aluminum and magnesium-containing) They 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, rifabutin and methylprednisolone in the blood when used simultaneously.
When azithromycin and cyclosporine are co-administered, a dose adjustment of cyclosporine is necessary. With simultaneous use of digoxin and azithromycin, it is necessary to monitor the concentration of digoxin in the blood, since many macrolides increase the absorption of digoxin in the intestine, thereby increasing its Cmax.
When used simultaneously with derivatives of ergotamine and dihydroergotamine, it is possible to increase the toxic effect (vasospasm, dysesthesia) of the latter.
If necessary, simultaneous use with indirect anticoagulants (warfarin, etc. coumarin-type anticoagulants) it is recommended to monitor prothrombin time.
Concomitant use of terfenadine or cisapride and macrolide antibiotics has been found to cause arrhythmia and prolongation of the QT interval. Based on this, the above-mentioned complications cannot be excluded with the combined use of azithromycin and terfenadine.
During simultaneous use of azithromycin and zidovudine, azithromycin had little effect on the pharmacokinetics, including the renal excretion of zidovudine or its glucuronide metabolite; azithromycin interacts weakly with the isoenzymes of cytochrome P-450, it is not revealed that azithromycin is involved in the pharmacological interactions, similar to erythromycin and other macrolides, azithromycin is not an inducer and inhibitor of the isozymes of cytochrome P-450.
With simultaneous use of azithromycin and rifabutin, in rare cases, neutropenia may develop, the mechanism of development of which, as well as the presence of a causal relationship with taking the drug, have not been established.
Concomitant use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times a day) causes an increase in the steady-state concentration of azithromycin in blood plasma, no clinically significant side effects were observed, and dose adjustment of azithromycin with its simultaneous use with nelfinavir is not required.
There have been isolated reports of rhabdomyolysis in patients taking concomitant azithromycin and statins.
How to take, course of use and dosage
Set individually, taking into account the nosological form, severity of the disease and sensitivity of the pathogen.
Adults inside-0.25-1 g 1 time/day; children-5-10 mg / kg 1 time/day. The duration of admission is 2-5 days.
Special instructions
When prescribing to patients with diabetes mellitus, as well as with a low-calorie diet, it should be taken into account that the suspension contains sucrose (3.7 g/5 ml or 0.3 XE/5 ml).
If one dose of the drug is missed – the missed dose should be taken as early as possible, and subsequent doses should be taken at intervals of 24 hours. It is necessary to follow the scheme recommended in the instructions and the duration of taking the drug.
Azithromycin is contraindicated in patients with severe hepatic impairment.
In patients with mild to moderate hepatic impairment, azithromycin should be administered with caution due to the possibility of developing fulminant hepatitis and severe hepatic insufficiency. In the presence of symptoms of impaired liver function (rapidly increasing asthenia, jaundice, darkening of the color of urine, tendency to bleeding, hepatic encephalopathy), azithromycin therapy should be discontinued and a study of the functional state of the liver should be conducted.
With impaired renal function: in patients with a glomerular filtration rate of 10-80 ml/min, no dose adjustment is required, and Azitrox therapy should be performed with caution under the control of renal function.
There are no data on a possible interaction between azithromycin and derivatives of ergotamine and dihydroergotamine, but due to the development of ergotism when taking macrolides simultaneously 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. Taking medications that inhibit intestinal motility is contraindicated. If diarrhea develops while taking azithromycin, as well as 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded.
With delayed ventricular repolarization syndrome – the QT prolongation syndrome – taking macrolides, including azithromycin, increases the risk of arrhythmia.
Caution should be exercised when prescribing azithromycin in patients with 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 agents, patients with azithromycin should be regularly examined for the presence of non-susceptible microorganisms and signs of superinfections, including fungal infections.
Influence on the ability to drive vehicles and mechanisms.
In case of adverse reactions from the central nervous system, patients are advised to refrain from driving vehicles or engaging in other potentially dangerous activities that require increased concentration of attention, speed of psychomotor and motor reactions.
Form of production
Powder for the preparation of a suspension for oral use
Storage conditions
Store in a dry place, protected from light, at room temperature. Keep out of reach of children.
Shelf
life is 2 years. Prepared suspension – no more than 5 days.
Active ingredient
Azithromycin
Conditions of release from pharmacies
By prescription
Dosage form
suspension for oral use
Purpose
Children over 6 months of age, Children as prescribed by a doctor, Adults as prescribed by a doctor
Indications
Urinary Tract infections, Bronchitis, Otitis Media, Pharyngitis, Tonsillitis, Skin Infections, Infectious Diseases, Sore Throat, Pneumonia, Sinusitis, Sinusitis, Pneumonia, Respiratory Tract Infections, Vaginal Infections, Urethritis
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Side effects of Azitrox, 100mg/5ml suspension, 20ml
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