Composition, form of production and packaging
Lyophilizate for the preparation of a solution for infusions in the form of powder or packed in a tablet of white or almost white color.
1 f.
azithromycin (in the form of dihydrate) 500 mg
Excipients: citric acid monohydrate 110 mg, mannitol 146 mg, sodium hydroxide to pH 6.0-7.0.
glass bottles (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Azithromycin is a macrolide antibiotic of the azalide group. Reversibly binding to the 50S subunit of ribosomes of bacterial cells, disrupts the translocation of the growing polypeptide chain from the aminoacyl region to the peptide one, which
leads to suppression of protein synthesis in bacterial cells.
Sensitive: aerobic Gram-positive microorganisms - Staphylococcus aureus (methicillin-sensitive), Streptococcus pneumoniae (penicillin-sensitive), Streptococcus pyogenes; aerobic gram-negative microorganisms - Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis, Pasteurella multocida, Neisseria gonorrhoeae; anaerobic microorganisms - Clostridium perfringens, Fusobacterium spp., Prevotella spp., Porphyromonas spp .; other - Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.
Moderately sensitive: Streptococcus pneumoniae (moderately sensitive or resistant to penicillin).
Stable: aerobic Gram-positive microorganisms - Enterococcus faecalis, beta-hemolytic Streptococcus spp. group A, Staphylococcus spp. (methicillin-resistant), incl.Staphylococcus aureus, resistant to erythromycin and other macrolides, lincosamides; anaerobes: Bacteroides fragilis.
PHARMACOKINETICS
Azithromycin rapidly penetrates from the blood plasma into the tissue. Concentrating in phagocytes and not violating their function, azithromycin migrates to the focus of inflammation, accumulating directly in infected tissues. The pharmacokinetic profile of azithromycin is characterized by a low concentration in the blood plasma and a high concentration in the tissues.
In healthy volunteers, with intravenous infusion of azithromycin 500 mg (solution concentration 1 mg / ml) for 3 hours, the C max drug in the blood plasma was 1.1 μg / ml, with a baseline concentration of 0.18 μg / ml. Similar values ​​were found in patients with community-acquired pneumonia who received the same therapy for 2 to 5 days (C max 3.6 μg / ml, at a baseline concentration of 0.2 μg / ml).
T 1/2 of the drug is 65-72 hours.
Binding to plasma proteins decreases with an increase in the concentration of azithromycin in the blood. Azithromycin has a protein binding percentage of 51 at a concentration of 0.02 Ојg / ml and 7% at a concentration of 2 Ојg / ml. After intravenous administration, azithromycin is distributed to most tissues and body fluids. A high level of observed V d (average 32 l / kg) and plasma clearance (10.8 ml / min / kg) suggests that a prolonged T 1/2 of the drug is a consequence of the accumulation of antibiotic in tissues followed by its slow release. 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; accumulates in a medium with a low pH, in lysosomes (which is especially important for the eradication of intracellular pathogens). It is also transported by phagocytes: polymorphonuclear leukocytes and macrophages. It penetrates the membranes of cells and creates high concentrations in them.
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. The body remains in effective concentrations for 5-7 days after the administration of the last dose.
The main pathway of biotransformation is N-demethylation in the liver. It is excreted by the intestine, mostly unchanged. A small amount of the drug is excreted by the kidneys. In the first day, 11% of the kidneys are excreted, and after 5 days, 14% of the IV dose.
INDICATIONS
- Community-acquired pneumonia of severe course caused by Chlamydia pneumoniae, Haemophilusi nfluenzae, Legionella pneumophila, Moraxella catarrhalis, Mycoplasma pneumoniae, Staphylococcus aureus or Streptococcus pneumoniae;
- Infectious-inflammatory diseases of small pelvic organs of severe course (endometritis and salpingitis) caused by Chlamydia trachomatis, Neisseria gonorrhoeae or Mycoplasma hominis.
DOSING MODE
The drug should be used only in inpatient medical institutions. Recommended doses for iv administration of azithromycin in the treatment of adults and patients older than 16 years with the following diseases:
Community-acquired pneumonia (EP)
500 mg once / day intravenously for at least 2 days. In / in the administration should be replaced by the subsequent oral administration of azithromycin in the form of a single daily dose of 500 mg until the complete completion of a 7-10 day general course of treatment.
Infectious-inflammatory diseases of the pelvic organs
500 mg once / day intravenously for at least 2 days. In / in the administration should be replaced by the subsequent oral administration of azithromycin in the form of a single daily dose of 250 mg until the complete completion of a 7-day general course of treatment.
The timing of the transition to oral treatment is determined in accordance with the data of the clinical examination.
For patients with moderate impairment of liver and kidney function (creatinine clearance> 40 ml / min) dose adjustment is not needed.
Rules for the preparation of solution
Solution for infusion is prepared in 2 stages:
Stage 1 - preparation of the reconstituted solution: 4.8 ml of sterile water for injections are added to a bottle containing 500 mg of the preparation and thoroughly shaken until the powder is completely dissolved. In 1 ml of the resulting solution contains 100 mg of azithromycin. The prepared solution remains stable for 24 hours at room temperature.
Stage 2 - reconstitution of the reconstituted solution (100 mg / ml) is carried out immediately before administration according to the table below.
The concentration of azithromycin in the infusion solution The amount of solvent
1.0 mg / ml 500 ml
2.0 mg / ml 250 ml
The reconstituted solution is introduced into a vial with a solvent (0.9% sodium chloride solution, 5% dextrose, Ringer's solution) until a final concentration of azithromycin is 1-2 mg / ml in the infusion solution.
A solution of hemomycin can not be administered intravenously or intravenously. It is recommended to enter the prepared solution IV in the form of infusion, drip (at least 1 hour).
Before injection, the solution is visually inspected. If the finished solution contains particles of the substance, then it should not be used. The prepared solution is stable at room temperature for 24 hours.
SIDE EFFECT
From the side of the central nervous system: dizziness / vertigo, headache, drowsiness convulsions; paresthesia, asthenia, insomnia, increased excitability, fainting, aggressiveness, anxiety, nervousness.
From the senses: tinnitus, reversible hearing loss down to deafness (when taking high doses for a long time), visual impairment, a violation of the perception of taste and smell.
From the cardiovascular system: a feeling of heartbeat, arrhythmia, including ventricular tachycardia, an increase in the QT interval, bidirectional ventricular tachycardia, a decrease in blood pressure.
On the part of the digestive system: nausea, vomiting, diarrhea, abdominal pain and lubrication, loose stools, flatulence, digestive disorders, cholestatic jaundice, hepatitis, gastritis, changes in liver function tests, constipation, discoloration, pseudomembranous colitis, pancreatitis, liver necrosis , hepatic insufficiency (possibly fatal).
From the blood and lymphatic systems: thrombocytopenia, neutropenia, leukopenia, neutrophilia.
Allergic reactions: itching, skin rashes, angioedema, hives, photosensitivity, anaphylactic reaction, including edema (in rare cases, fatal), erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
From the musculoskeletal system: arthralgia.
From the genitourinary system: nephritis, acute renal failure.
Local reactions: pain and inflammation at the injection site.
Other: Candidiasis, incl. oral cavity and genital organs, fatigue, malaise, anorexia, vaginitis.
CONTRAINDICATIONS
- severe violations of the liver and kidneys;
- Children's age till 16 years;
- simultaneous administration with ergotamine and dihydroergotamine;
- hypersensitivity to antibiotics of macrolides.
With caution: with moderate violations of the liver and kidney function, patients with a disorder or predisposition to arrhythmias and lengthening of the QT interval, with the co-administration of terfenadine, warfarin, digoxin.
PREGNANCY AND LACTATION
The use of the drug during pregnancy is possible only in cases when the benefit from its use for the mother exceeds the possible risk to the fetus. During lactation, breastfeeding is suspended.
APPLICATION FOR FUNCTIONS OF THE LIVER
For patients with moderate impairment of kidney function (creatinine clearance> 40 ml / min) dose adjustment is not needed.
Contraindicated:
- severe renal dysfunction.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
For patients with moderate impairment of liver function, dose adjustment is not needed.
Contraindicated:
severe hepatic impairment.
APPLICATION FOR CHILDREN
The safety of the use and effectiveness of the injectable form of the drug Hemomycin in children under 16 years is not established.
SPECIAL INSTRUCTIONS
The safety of the use and effectiveness of the injectable form of the drug Hemomycin in children under 16 years is not established.
Do not administer the drug with longer courses than indicated in the instructions. pharmacokinetic properties of azithromycin allow the use of a short dosing regimen.
It is possible to attach superinfection (including fungal) in the treatment with Hemomycin (as in any antibiotic therapy).
When using the drug Hemomycin, diarrhea / pseudomembranous colitis caused by Clostridium difficile can develop. In this regard, patients with diarrhea should be carefully observed.
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 likelihood of side effects from the central nervous system, care should be taken when driving vehicles and mechanisms.
OVERDOSE
Symptoms: severe nausea, temporary loss of hearing, vomiting, diarrhea, abdominal pain, impaired liver function.
Treatment: symptomatic.
DRUG INTERACTION
Azithromycin does not affect the concentration of carbamazepine, cimetidine, didanosine, efavirenz, fluconazole, indinavir, midazolam, theophylline, triazolam, trimethoprim / sulfamethoxazole, rifabutin and methylprednisolone in the blood together.
If it is necessary to share with cyclosporine, it is recommended to monitor the content of cyclosporine in the blood.
With the combined use 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.
When combined with indirect anticoagulants (warfarin, other anticoagulants coumarin series), it is recommended that patients carefully monitor prothrombin time.
Simultaneous use of terfenadine and antibiotics of the macrolide class causes arrhythmia and lengthening of the QT interval. It is necessary to take into account these data in the joint use of terfenadine and azithromycin.
When combined with nelfinavir may increase the incidence of side effects from azithromycin.
The possibility of inhibiting the isozyme CYP3A4 with azithromycin should be considered when combined with cyclosporine, terfenadine, ergot alkaloids, cisapride, pimozide, quinidine, astemizole and other drugs metabolized by this enzyme.
With the joint use of azithromycin and zidovudine, azithromycin does not affect the pharmacokinetic parameters of zidovudine in the blood plasma or on excretion by the kidneys of its and its metabolite glucuronide. Nevertheless, the concentration of the active metabolite - phosphorylated zidovudine - increases in mononuclear cells of peripheral vessels. So far, the clinical significance of this fact has not been determined.
With the joint use of azithromycin with ergotamine and dihydroergotamine, their toxic effect (vasospasm, dysesthesia) is possible.
Pharmaceutically incompatible with heparin.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
Store at a temperature of 10 В° to 25 В° C. Keep out of the reach of children. Shelf life - 3 years.
Do not use after the expiration date printed on the package.
