Composition, form of production and packaging
Capsules are hard gelatinous, yellowish white with "AZIWOK" and "WOCKHARDT" marks in black; the contents of the capsules are white or almost white powder; the size of capsule в„–0.
azithromycin 250 mg
Excipients: lactose, corn starch, magnesium stearate, sodium lauryl sulfate.
6 pcs. - packings of cellular contour (1) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
Antibacterial means of a wide spectrum of action, azalide, acts bacteriostatically. Linking to the 50S subunit of the ribosomes, inhibits peptidranslokase at the stage of translation, suppresses protein synthesis, slows the growth and multiplication of bacteria, has a bactericidal effect at high concentrations.
Azithromycin acts on extra- and intracellular pathogens.
Sensitive: aerobic gram-positive microorganisms - Streptococcus pneumoniae (penicillin- sensitive ), Streptococcus pyogenes, Staphylococcus aureus (methicillin-sensitive); aerobic gram-negative microorganisms - Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, Haemophilus parainfluenzae, Pasteurella multocida, Neisseria gonorrhoeae; anaerobic microorganisms - Prevotella spp., Clostridium perfringens, Fusobacterium spp., Porphyromonas spp .; other - Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.
Moderately sensitive or insensitive: aerobic Gram-positive microorganisms - Streptococcus pneumoniae (moderately sensitive or resistant to penicillin).
Stable: aerobic Gram-positive microorganisms - Enterococcus faecalis, Staphylococcus spp., (Methicillin-resistant); anaerobes - the Bacteroides fragilis group.
Streptococcus pneumoniae, beta-hemolytic Streptococcus spp. Group A, Enterococcus faecalis and Staphylococcus aureus (including methicillin-resistant strains) resistant to erythromycin and other macrolides, lincosamides, are resistant to azithromycin.
Absorption is high, acid-fast, lipophilic. Bioavailability after a single dose of 0.5 g - 37% (the effect of "first pass" through the liver), C max after oral intake 0.5 g - 0.4 mg / l, time to reach C max - 2.5-2.9 h; in tissues and cells the concentration is 10-50 times higher than in the blood plasma, V d - 31.1 l / kg.
Easily passes through the histohematological barriers. It penetrates well into the respiratory tract, genito-urinary organs and tissues, incl. prostate, in the skin and soft tissues.
It penetrates through cell membranes and creates high concentrations in them, accumulates in lysosomes (which is especially important for the eradication of intracellularly located pathogens). It is also transported by phagocytes: polymorphonuclear leukocytes and macrophages.
The concentration in the foci of infection is significantly higher (by 24-34%) than in healthy tissues, and correlates with the severity of the inflammatory edema. It remains in effective concentrations for 5-7 days after the last dose.
The connection with plasma proteins is 7-50% (inversely proportional to the concentration in the blood).
In the liver, demethylated, inactive metabolites are formed. In the metabolism of the drug involved isozymes CYP3A4, CYP3A5, CYP3A7, the inhibitor of which it is.
Plasma clearance - 630 ml / min. T 1/2 between 8 and 24 hours after admission - 14-20 h, T 1/2 in the interval from 24 to 72 h - 41 h. 50% is excreted with bile in unchanged form, 6% - with kidneys.
Pharmacokinetics in special clinical cases
Eating significantly changes the pharmacokinetics: C max and AUC decrease by 52% and 43%, respectively.
In elderly men (65-85 years) pharmacokinetic parameters do not change, in women C max increases (by 30-50%).
Infectious-inflammatory diseases caused by microorganisms sensitive to the preparation:
- infections of the upper respiratory tract and ENT organs (pharyngitis, tonsillitis, sinusitis, otitis media);
- Infections of the lower respiratory tract (pneumonia (including caused by atypical pathogens), bronchitis);
- skin and soft tissue infections (acne vulgaris (medium severity), erysipelas, impetigo, secondarily infected dermatoses);
- urinary tract infections (urethritis, cervicitis (caused by Chlamydia trachomatis));
- Lyme disease (initial stage - erythema migrans).
Adults and children over 12 years of age weighing more than 45 kg: inside, 1 hour before or 2 hours after meals, once a day.
With infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues - 0.5 g / day for 1 reception for 3 days (exchange dose - 1.5 g).
When acne vulgaris - 0.5 g / day for 1 reception for 3 days, then 0.5 g / day 1 time per week for 9 weeks. The first weekly capsule should be taken 7 days after the first daily capsule (8 days from the start of treatment), the next 8 weekly capsules - at intervals of 7 days.
With infections of the urinary tract (urethritis or cervicitis) - once 1 g.
In Lyme disease - for the treatment of stage I (erythema migrans) - 1 g on the first day and 0.5 g daily from 2 to 5 days (course dose - 3 g).
From the side of the circulatory system: thrombocytopenia, neutropenia .
From the nervous system: dizziness / vertigo, headache, cramps, drowsiness, paresthesia, asthenia, insomnia, hyperactivity, aggressiveness, anxiety, nervousness.
From the senses: tinnitus, reversible hearing loss down to deafness (when taking high doses for a long time), a violation of the perception of taste and smell.
From the cardiovascular system: a feeling of heartbeat, arrhythmia, ventricular tachycardia, an increase in the QT interval, bidirectional ventricular tachycardia.
From the digestive system: nausea, vomiting, diarrhea, abdominal pain / spasms, flatulence, digestive disorders, anorexia, constipation, discoloration of the tongue, pseudomembranous colitis, cholestatic jaundice, hepatitis, changes in liver function tests, hepatic insufficiency, liver necrosis (possibly with a fatal outcome).
Allergic reactions: itching, skin rashes, angioedema, urticaria, eosinophilia, anaphylactic reaction, including Quincke's edema (in rare cases, fatal), erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome.
From the musculoskeletal system: arthralgia.
From the genitourinary system: interstitial nephritis, acute renal failure.
Other: vaginitis, candidiasis, photosensitivity.
- severe hepatic and / or renal insufficiency;
- simultaneous reception of ergotamine and dihydroergotamine;
- lactation period;
- Children's age (up to 12 years with a body weight of less than 45 kg, for this dosage form);
- intolerance of lactose, insufficiency of lactase, glucose-galactose malabsorption (because the composition of the drug includes lactose);
- hypersensitivity (including to other macrolides).
With caution: moderate dysfunction of the liver and kidneys; arrhythmias (including predisposition to arrhythmias and prolongation of the QT interval); simultaneous reception with terfenadine, warfarin, digoxin.
PREGNANCY AND LACTATION
In pregnancy, the drug is used only if the intended benefit to the mother exceeds the potential risk to the fetus.
During lactation during the treatment should stop breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in severe renal dysfunction.
With caution: moderate renal dysfunction.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in severe violations of liver function.
With caution: moderate dysfunction of the liver.
APPLICATION FOR CHILDREN
Protivoapokazan in childhood (up to 12 years with a body weight of less than 45 kg, for this dosage form).
In case of missed intake of a single dose of the drug, the missed dose should be taken as soon as possible, and the following - with interruptions of 24 hours.
Just as with any antibiotic therapy, with the treatment of azithromycin, it is possible to attach superinfection (including fungal).
The drug should be taken at least 1 hour before or 2 hours after taking antacid preparations.
After the withdrawal of the treatment, hypersensitivity reactions in some patients may persist, which requires specific therapy under the supervision of a physician.
Influence on ability to drive vehicles and mechanisms
Given the side effects of the drug from the side of the central nervous system, care must be taken when driving vehicles and working with mechanisms that require concentration.
Symptoms: severe nausea, temporary loss of hearing, vomiting, diarrhea.
Treatment: gastric lavage, symptomatic therapy, hemodialysis is not effective.
Antacids do not affect the bioavailability of azithromycin, but reduce Cmax in the blood by 30%, so the drug should be taken 1 hour before or 2 hours after taking these drugs and food.
Azithromycin does not affect the concentration of carbamazepine, didanosine, rifabutin and methylprednisolone in the blood in a joint application.
In parenteral administration, azithromycin does not affect the concentration of cimetidine, efavirenz, fluconazole, indinavir, midazolam, triazolam, co-trimoxazole in the blood in a joint application, but do not exclude the possibility of such interactions in the administration of azithromycin for oral administration.
Azithromycin does not affect the pharmacokinetics of theophylline, however, when combined with other macrolides, the concentration of theophylline in the blood plasma may increase.
If it is necessary to share with cyclosporine, it is recommended to monitor the content of cyclosporine in the blood. Despite the fact that there is no data on the effect of azithromycin on the change in the concentration of cyclosporine in the blood, other representatives of the macrolide class are able to change its concentration in the blood plasma.
With the joint administration of digoxin and azithromycin, it is necessary to monitor the concentration of digoxin in the blood, many macrolides increase absorption of digoxin in the intestine, thereby increasing its concentration in the blood plasma.
If it is necessary to share with warfarin, careful monitoring of prothrombin time is recommended.
It was found that simultaneous reception of terfenadine and antibiotics of the macrolide class causes arrhythmia and lengthening of the QT interval. Proceeding from this, it is impossible to exclude the aforementioned complications in the joint administration of terfenadine and azithromycin.
Since it is possible to inhibit the isofermite of CYP3A4 with azithromycin in parenteral form when combined with cyclosporine, terfenadine, ergot alkaloids, cisapride, pimozide, quinidine, astemizole and other drugs metabolized by this enzyme, the possibility of such interaction in the administration of azithromycin for administration inside.
With the joint administration of azithromycin and zidovudine, azithromycin does not affect the pharmacokinetic parameters of zidovudine in the blood plasma or on the excretion of its kidney and its glucuronated metabolite. Nevertheless, the concentration of the active metabolite - phosphorylated zidovudine - increases in mononuclear cells of peripheral vessels. The clinical significance of this fact is not clear.
With the simultaneous administration of macrolides with ergotamine and dihydroergotamine, their toxic effect is possible.
TERMS OF RELEASE FROM PHARMACY
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a dark place at a temperature of no higher than 30 В° C. Keep out of the reach of children. Shelf life - 2 years.