Composition, form of production and packaging
Lyophilizate for solution for infusion 1 amp.
doxycycline (in the form of hydrochloride) 100 mg
Excipients: sodium disulfite - 6 mg, disodium edetate - 0.02 mg.
100 mg - ampoules (5) - packs of cardboard with partitions.
100 mg - ampoules (10) - packs of cardboard with partitions.
Lyophilizate for solution for infusion 1 fl.
doxycycline (in the form of hydrochloride) 100 mg
Excipients: sodium disulfite - 6 mg, disodium edetate - 0.02 mg.
100 mg - bottles (5) - contour plastic packaging (1) - cardboard packs.
100 mg - bottles (5) - contour plastic packaging (2) - cardboard packs.
100 mg - bottles (5) - packings contour mesh (1) - packs cardboard.
100 mg - bottles (5) - packings contour mesh (2) - packs cardboard.
100 mg - bottles (50) - packings contour mesh (1) - cardboard boxes.
100 mg - bottles (50) - contour plastic packaging (1) - cardboard boxes.
Lyophilizate for solution for infusion 1 amp.
doxycycline (in the form of hydrochloride) 200 mg
Excipients: sodium disulfite - 12 mg, disodium edetate - 0.04 mg.
200 mg - ampoules (5) - packs of cardboard with partitions.
200 mg - ampoules (10) - packs of cardboard with partitions.
Lyophilizate for solution for infusion 1 fl.
doxycycline (in the form of hydrochloride) 200 mg
Excipients: sodium disulfite - 12 mg, disodium edetate - 0.04 mg.
200 mg - bottles (5) - contour plastic packaging (1) - cardboard packs.
200 mg - bottles (5) - contour plastic packaging (2) - cardboard packs.
200 mg - bottles (5) - packings contour mesh (1) - packs cardboard.
200 mg - bottles (5) - packings contour mesh (2) - packs cardboard.
200 mg - bottles (50) - packings contour mesh (1) - cardboard boxes.
200 mg - bottles (50) - contour plastic packaging (1) - cardboard boxes.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Doxycycline is a semisynthetic antibiotic from the group of tetracyclines with a wide spectrum of activity and has a bacteriostatic effect. Penetrating into the cell, acts on intracellularly located pathogens. Suppresses the synthesis of proteins in a microbial cell, disrupting the binding of transport aminoacyl ribonucleic acids to the 30S subunit of the ribosomal membrane.
Doxycycline in vitro is active against gram-positive microorganisms - Staphylococcus spp. (including Staphylococcus aureus, Staphylococcus epidermidis),
Streptococcusspp. (including Streptococcuspneumoniae), Clostridiumspp., Listeriaspp .; and Gram-negative microorganisms - Neisseriagonorrhoeae, Neisseriameningitidis, Haemophilusinfluenzae, Klebsiellaspp., Entamoebahistolytica, Escherichiacoli, Enterobacter, Salmonellaspp., Yersiniaspp. (formerly Pasteurella spp), Bacteroides spp., Treponema spp. (including strains resistant to other antibiotics, for example, to modern penicillins and cephalosporins). The most sensitive are Haemophilus influenzae (91-96%) and extracellular parasites.
Doxycycline is active against most pathogens of especially dangerous and dangerous infectious diseases: plague (Y. pestis), tularemia (Francisella tularensis), anthrax (Bacillus anthracis) microbes, cholera vibrio (V. cholerae), Rickettsia spp. brucellosis (Brucella spp.), causative agents of sapa, ornithosis, psittacosis, legionella, trachoma, venereal granuloma (Chlamidia pneumoniae, Chlamydia trachomatis, Chlamydia granulomatosis). It acts on most strains of proteium, Pseudomonas aeruginosa and fungi.
By the degree of antibacterial activity, doxycycline is superior to natural tetracyclines. In contrast to tetracycline and oxytetracycline, it has higher therapeutic efficacy, even with 10 times lower doses and a longer action. To a lesser extent than other antibiotics of the tetracycline series inhibits the intestinal flora, it differs from them by a more complete absorption and longer duration of action. There is cross-resistance to other tetracyclines, as well as to penicillins.
PHARMACOKINETICS
After a single infusion of 100 mg of doxycycline lasting 60 minutes (concentration of 0.4 mg / ml solution) in patients with normal renal function, C max is 2.5 Ојg / ml; after a two-hour infusion of 200 mg of the drug (concentration of the solution 0.4 mg / ml), C max is about 3.6 Ојg / ml. It has a higher degree of lipid solubility than tetracycline and oxytetra-cyclin, so it is well distributed in many organs and tissues (liver, kidney, lung, spleen, bones, teeth, prostate gland, eye tissues, pleural and ascitic fluids, bile, synovial exudate, exudate of the maxillary and frontal sinuses), where it creates high therapeutically significant concentrations. A low affinity for binding to calcium ions has been revealed. With repeated injections, the effect of cumulation of the drug is noted. It accumulates in the reticulo-endothelial system and bone tissue. In bones and teeth forms insoluble calcium complexes. Penetrates through the placental barrier, is determined in breast milk. Poor penetration into the cerebrospinal fluid (10-20% of the plasma level). High concentrations, 10-20 times higher in the blood plasma, are determined in bile. Communication with blood plasma proteins is 80-93%. The volume of distribution is 0.7 l / kg.
The half-life is 10-16 hours. 40% of the administered dose of doxycycline is excreted by the kidneys for 72 hours (of which 20-50% is unchanged), with severe renal failure, only 1-5%. Undergoes intestinal-hepatic recirculation; 20-60% is excreted through the intestine. In patients with impaired renal function or azotemia, an important route of elimination is the gastrointestinal tract. When hemodialysis, doxycycline is not removed from the blood serum.
INDICATIONS
Infectious-inflammatory diseases caused by microorganisms sensitive to the preparation:
- infections of the upper and lower respiratory tract (acute bronchitis, exacerbation of chronic bronchitis, tracheitis, bronchopneumonia, moderate and severe pneumonia, lung abscess, pleural empyema);
- infections of the ENT organs (otitis media, tonsillitis, sinusitis);
- infections of the genitourinary system (cystitis, pyelonephritis, prostatitis, urethritis, urethro-cystitis, urogenital mycoplasmosis, endometritis, endocervicitis, acute orchypididitis, gonorrhea);
- infection of the bile duct and gastrointestinal tract (cholecystitis, cholangitis, gastroenterocolitis, bacterial dysentery, diarrhea of ​​"travelers"); infections of the skin and soft tissues (phlegmon, abscesses, furunculosis, infected burns, wounds);
- infectious diseases of the eyes;
- syphilis, yawsiniosis, legionellosis, rickettsiosis, chlamydia of various locations (including prostatitis and proctitis), fever Ky, spotty fever of the Rocky Mountains, typhus (including swelling, tick-borne recurrent), Lyme disease (borreliosis) I st. , bacillary and amoebic dysentery, tularemia, cholera, actinomycosis, malaria;
- in the combination therapy - leptospirosis, trachoma, psittacosis, ornithosis, granulocyte erlichiosis; whooping cough, brucellosis, osteomyelitis; sepsis, subacute septic endocarditis, peritonitis; prevention of postoperative purulent complications;
- prevention of malaria caused by Plasmodium falciparum, during short trips (less than 4 months) in areas where strains resistant to chloroquine and / or pyrimethamine sulfadoxine are common.
DOSING MODE
Intravenous administration (iv) Doxycycline is preferred in severe forms of purulent-septic diseases, when it is necessary to quickly create a high concentration of the drug in the blood and tissues, as well as in cases when taking the drug inside is difficult. It is recommended step therapy, that is, the transition to taking dosage forms of doxycycline for oral administration, as soon as it becomes possible. For adults, the usual daily dose of Doxycycline is 200 mg / day, administered once a day, or 100 mg every 12 hours. The duration of therapy is determined by the form and severity of the infection; iv injections are administered 3-5 days, if necessary and / or well tolerated, parenteral administration is extended to 7 days; in the subsequent (according to the indications!) go to the reception of Doxycycline inside.
In inflammatory diseases of the small pelvis, women in the acute stage of the disease are administered IV in 100 mg every 12 hours; Combined therapy with cephalosporins of the third generation is recommended. With a positive response to therapy and stabilization of the patient's condition, continue the therapy with doxycycline dosage forms for oral administration of 100 mg twice a day for 14 days.
For the treatment of syphilis (primary or secondary), the dose of Doxycycline is 300 mg / day; treatment continues for at least 10 days (according to the indications, in the process it is possible to replace intravenously with the introduction of the drug inside).
Given the characteristics of pharmacokinetics and the primary excretion of doxycycline through the intestines with bile, patients with impaired renal function are administered at usual therapeutic doses, no dose adjustment is required.
In children older than 8 years, the dose is calculated based on body weight, the recommended daily dose on the first day of therapy is 4 mg / kg in 1 or 2 injections, then 2-4 mg / kg per day in 1 or 2 administrations depending on the severity of the infection . In children with a body weight of more than 45 kg, the doses indicated for adults are used.
Rules for the preparation of solutions
Preparation of Doxycycline solution for intravenous infusion is performed in two stages:
Stage 1 - the contents of the vial (ampoules) with 100 mg or 200 mg of sterile lyophilisate are diluted with 10 ml of sterile water for injection or 0.9% solution of sodium chloride.
2 stage - the Doxycycline solution obtained at the initial dilution is added to 250 or 500 ml of one of the following infusion media: 0.9% sodium chloride solution or 5% dextrose (glucose) solution. The recommended range of concentrations of the ready solution for infusions is from 0.1 mg / ml to 1 mg / ml.
The duration of the infusion according to the dose (0.1 or 0.2 g) and the volume of the prepared solution is about 1-4 hours at a rate of 60-80 cap / min. The recommended duration of infusion of a solution containing 100 mg of doxycycline at a concentration of 0.5 mg / ml is -60 minutes.
SIDE EFFECT
From the side of the nervous system: a benign increase in intracranial pressure (loss of appetite, vomiting, headache, edema of the optic nerve disc), toxic effect on the central nervous system (dizziness or instability), the condition quickly stops after doxycycline cancellation.
From the gastrointestinal tract: nausea, diarrhea, constipation, enterocolitis (due to the proliferation of resistant strains of staphylococci).
Allergic reactions : maculopapular rash, skin itching, skin hyperemia, angioedema, anaphylactoid reactions, drug lupus erythematosus.
On the part of the hemopoiesis: hemolytic anemia, thrombocytopenia, neutropenia, eosinophilia.
From the urinary system : an increase in the concentration of urea nitrogen in the blood serum.
Local reactions : thrombophlebitis at the site of intravenous infusion, especially with prolonged therapy.
Other: photosensitization, superinfection; stable change in the color of tooth enamel, oropharyngeal, intestinal and vaginal candidiasis (one of the manifestations is inflammation in the anogenital zone of the perineum).
CONTRAINDICATIONS
- hypersensitivity to doxycycline and other tetracyclines;
- porphyria;
severe hepatic impairment;
- Lakopenia;
- Children's age to 8 years (the possibility of formation of insoluble complexes with calcium ions with deposition in the bone skeleton, enamel and dentin teeth);
- Myasthenia gravis;
- Pregnancy (II-IIItrimester), lactation period.
PREGNANCY AND LACTATION
Penetrates through the placental barrier, is determined in breast milk. In the experiment it was established that doxycycline can exert a toxic effect on fetal development (delay in the development of the skeleton).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in severe hepatic impairment and porphyria.
APPLICATION FOR CHILDREN
Contraindicated for children under 8 years.
SPECIAL INSTRUCTIONS
In connection with the possible development of photosensitivity, it is necessary to avoid sunlight and the effects of artificial ultraviolet irradiation during treatment and for 4-5 days after it.
With prolonged use, periodic monitoring of liver function, hematopoiesis is necessary.
The anti-anabolic effect characteristic of tetracyclines may be the reason for an increase in the concentration of urea nitrogen in the blood serum.
All tetracyclines form stable complexes with calcium ions in any bone-forming tissue, so the reception during the development of the teeth can cause long-term staining of the teeth in yellow-gray-brown color, as well as hypoplasia of the enamel. During infusion, the solution should be protected from exposure to direct sunlight, artificial ultraviolet radiation, and artificial light from other sources.
Doxycycline solution can not be mixed and simultaneously administered with other medicines.
May mask the manifestations of syphilis, in connection with which, if possible, a monthly serological analysis is necessary for 4 months. Perhaps a false increase in the level of catecholamines in urine when determined by the fluorescent method. In the study of the thyroid biopsy in patients who have been receiving doxycycline for a long time, it is possible to dark brown staining of the tissue in micro preparations without disturbing its function; function of the thyroid gland is not impaired. In the experiment, it has been established that doxycycline can have a toxic effect on the development of the fetus (delay in the development of the skeleton) - it blocks the metalloproteases (enzymes that catalyze the degradation of collagen and proteoglycans) in the cartilage. It leads to a reduction in lesions with deforming osteoarthritis.
DRUG INTERACTION
When combined with bactericidal antibiotics that disrupt the synthesis of the cell wall (penicillins, cephalosporins), a decrease in the effectiveness of the latter.Reduces the reliability of contraception and increases the frequency of bleeding "breakthrough" against the background of taking estrogen-containing oral contraceptives.
Ethanol, barbiturates, rifampicin, carbamazepine, phenytoin and other stimulants of microsomal oxidation, accelerating the metabolism of doxycycline, reduce its concentration in the blood plasma, which may require correction of the dose of this antibiotic. Simultaneous use of retinol helps increase intracranial pressure.
In connection with the suppression of the intestinal microflora reduces the prothrombin index, which requires correction of the dose of indirect anticoagulants.Pharmaceutically incompatible with other medicines.
TERMS OF RELEASE FROM PHARMACY
On prescription.
TERMS AND CONDITIONS OF STORAGE
In the dark place at a temperature of no higher than 25 В° C. Keep out of the reach of children. Shelf life - 2 years.
