Doxycycline

General characteristics. Structure:

Active agent: Doksitsilina a hydrochloride (in terms of doxycycline) – 0,1 g. Excipients: Potato starch; calcium stearate; sucrose (sugar). Gelatin capsules: Titanium dioxide, yellow quinolinic, sunset-yellow, methylparahydroxybenzoate, пропилпарагидроксибензоат, acetic acid, gelatin.

Pharmacological properties:

Semi-synthetic tetracycline, bacteriostatic antibiotic of a broad spectrum of activity. Getting in a cell, works on intracellularly located activators. Suppresses synthesis of proteins in a microbic cell, breaks communication transport aminoacyl-RNA with 30S in subunit of a ribosomalny membrane. To it are highly sensitive: gram-positive microorganisms of Staphylococcus spp. (including Staphylococcus aureus, Staphylococcus epidermidis), Streptococcus spp. (including Streptococcus pneumoniae), Clostridium spp., Listeria spp.; and gram-negative microorganisms: Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae, Klebsiella spp., Entamoeba histolytica, Escherichia coli, Shigella spp., Enterobacter, Salmonella spp., Yersinia spp. (before Pasteurella spp.), Bacteroides spp., Treponema spp. (including the strains steady against other antibiotics, for example to modern penicillin and cephalosporins). Haemophilus influenzae (91 – 96%) and intracellular pathogens are most sensitive. There is a cross other tetracyclines resistance, and also to penicillin. 

Pharmacokinetics. Absorption - bystry and high (about 100%). Has high degree of solubility in lipids and low affinity concerning calcium binding. After oral administration of 200 mg time of achievement of the maximum concentration (TCmax) – 2,5 h, the maximum concentration (Cmax) – 2,5 mkg/ml, in 24 h after reception – 1,25 mkg/ml. Communication with proteins of plasma – 80 – 93%. Well gets into bodies and fabrics; in 30 - 45 min. after intake it is found in therapeutic concentration in a liver, kidneys, lungs, a spleen, bones, teeth, a prostate gland, eye tissues, in pleural and ascitic liquids, bile, synovial exudate, exudate of Highmore's and frontal sinuses, in liquid of gingival furrows. Badly gets into medullispinal liquid (10-20% of plasma level). Gets through a placental barrier, is defined in maternal milk. Distribution volume – 0,7 l/kg. It is metabolized in a liver of 30 - 60%. An elimination half-life (T1/2) – 10 - 16 h (generally – 12 - 14 h, on average – 16,3 h). At repeated introductions drug can kumulirovat. Collects in reticuloendothelial system and a bone tissue. In bones and teeth forms insoluble complexes with calcium. It is removed with bile where it is found in high concentration. Is exposed to enterohepatic recirculation, it is removed with a fecal masses (20 – 60%); 40% of the accepted dose are allocated with kidneys for 72 h (from them 20 – 50% - in not changed look), at a heavy chronic renal failure - only 1 – 5%. At patients with a renal failure or an azotemia an important way of removal is gastrointestinal secretion.

Indications to use:

The infectious and inflammatory diseases caused by sensitive microorganisms: respiratory infections (pharyngitis, bronchitis acute and chronic, tracheitis, bronchial pneumonia, share pneumonia, lung abscess, pleura empyema);
infections of ENT organs (otitis, tonsillitis, sinusitis, etc.);
infections of urinogenital system (cystitis, pyelonephritis, prostatitis, an urethritis, an urethrocystitis, urogenital mycoplasmosis, an endometritis, an endocervicitis, acute orkhiepididimit; gonorrhea);
infections of biliary tract and digestive tract (cholecystitis, cholangitis, gastroenterocolitis, bacterial dysentery, diarrhea of "travelers");
infections of skin and soft tissues (the phlegmons, abscesses, furunculosis, felons infected burns, wounds, etc.);
infectious diseases of eyes, syphilis, frambeziya, иерсиниоз, legionellosis, rickettsiosis, clamidiosis of various localization (including prostatitis and proctitis), Ku's fever, spotty fever of the Rocky Mountains, typhus (including sypny, tick-borne returnable), disease Laima (borreliosis) I Art., bacillar and amoebic dysentery, tularemia, cholera, actinomycosis, malaria; as a part of a combination therapy - leptospirosis, trachoma, a psittacosis, an ornithosis, granulotsitarny эрлихиоз; whooping cough, brucellosis, osteomyelitis; sepsis, subacute septic endocarditis, peritonitis.
Prevention of postoperative purulent complications; the malaria caused by Plasmodium falciparum at short-term travel (less than 4 months) in the territory where the strains steady against chloroquine and/or Pyrimethaminum sulphadoxine are widespread.

Route of administration and doses:

Inside, adults and children with body weight have more than 45 kg an average daily dose – 0,2 g in the first day (is divided into 2 receptions - on 0,1 g 2 times a day), further on 0,1 g/days. At persistent infections of an urinary system –       0,2 g/days throughout the entire period of therapy.
At treatment of gonorrhea appoint on one of the following schemes: an acute uncomplicated urethritis - a course dose of 0,5 g (1 reception – 0,3 g, the subsequent 2 - on 0,1 g with an interval of 6 h) or 0,1 g/days before full treatment (at women) or on 0,1 g 2 times a day within 7 days (at men); at the complicated gonorrhea forms a course dose – 0,8 - 0,9 which is distributed on 6 - 7 receptions  (0,3 g - 1 reception, then with an interval of 6 h on 5 - 6 of the subsequent).
At treatment of syphilis - on 0,3 g/days within not less than 10 days.
At the uncomplicated infections of an urethra, neck of uterus and rectum caused by Chlamydia trachomatis appoint 0,1 g         2 times a day within not less than 7 days.
Infections of men's generative organs - on 0,1 g 2 times a day during   4 weeks.
Treatment of the malaria steady against chloroquine – 0,2 g/days within 7 days (in combination with shizontotsidny medicines - quinine); prevention of malaria – 0,1 g of 1 times a day for 1 - 2 day to a trip, then daily during a trip and during 4 weeks after return; to children 8 years - 0,002 g/kg of 1 times a day are more senior.
Diarrhea of "travelers" (prevention) – 0,2 g in the first day of a trip (for 1 reception or on 0,1 g 2 times a day), further on 0,1 g of 1 times a day during all stay in the region (no more than 3 weeks).
Treatment of a hay fever – 0,1 g in 2 times a day within 7 days; prevention of a hay fever – 0,2 g once a week during stay in the unsuccessful area and 0,2 g at the end of a trip.
Prevention of infections after medical abortion – 0,1 g for 1 h before abortion and 0,2 g - in 30 min. after.
The maximum daily doses for adults - to 0,3 g/days or to 0,6 g/days within 5 days at heavy gonococcal infections.
Children have 9 - 12 years with body weight to 45 kg an average daily dose – 0,004 g/kg in the first day, further - on 0,002 g/kg a day (in 1 - 2 reception). At the heavy course of infections it is appointed each 12 h on 0,004 g/kg.
In the presence of a heavy liver failure decrease in a daily dose of doxycycline as at the same time there is its gradual accumulation in an organism (risk of a hepatotoxic action) is required.

Features of use:

For prevention of local irritative action (an esophagitis, gastritis, an ulceration of a mucous membrane of digestive tract) reception with a large amount of liquid, food is recommended in the afternoon.

Due to the possible development of a photosensitization restriction of insolation is necessary during treatment and within 4-5 days after it.

At long use periodic control of function of kidneys, a liver, bodies of a hemopoiesis is necessary.

Can mask displays of syphilis in this connection at a possibility of a mikstinfektion monthly carrying out serologic assay for 4 months is necessary.

Appointment during development of teeth can become the reason of irreversible change of their color.

Perhaps false increase in level of catecholamines in urine at their definition by a fluorescent method. At a research of a bioptat of a thyroid gland at patients, it is long receiving doxycycline, perhaps dark brown prokrashivaniye of fabric in microdrugs without disturbance of its function.

Side effects:

From a nervous system: high-quality increase in intracranial pressure (a loss of appetite, vomiting, a headache, a papilledema), toxic action on the central nervous system (dizziness or instability). From the alimentary system: nausea, locks or diarrhea, a glossitis, a dysphagy, an esophagitis (including erosive), gastritis, an ulceration of a stomach and duodenum, a coloenteritis (due to proliferation of resistant strains of stafilokokk), an inflammation in an anogenitalny zone of a crotch. Allergic reactions: makulopapulezny rash, skin itch, dermahemia, Quincke's disease, anaphylactoid reactions, medicinal lupus erythematosus. From bodies of a hemopoiesis: hemolitic anemia, thrombocytopenia, neutropenia, eosinophilia. Other: photosensitization, superinfection; steady discoloration of an adamantine substance of tooth. Fungal infections (vaginitis, glossitis, stomatitis, proctitis), dysbacteriosis. 
Use with other medicines Absorption is reduced by the antacids containing aluminum, magnesium, calcium, food, calciferous (milk, cottage cheese), iron preparations, Natrii hydrocarbonas, magniysoderzhashchy laxatives, Colestyraminum and колестипол therefore their use has to be divided by an interval of 3 h Due to the suppression of intestinal microflora reduces a prothrombin ratio that demands dose adjustment of indirect anticoagulants. At a combination to the bactericidal antibiotics breaking synthesis of a cell wall (penicillin, cephalosporins), efficiency of the last decreases. Reduces reliability of contraception and increases the frequency of bleedings of "break" against the background of reception of estrogensoderzhashchy oral contraceptives. Ethanol, barbiturates, rifampicin, carbamazepine, Phenytoinum, etc. stimulators of a microsomal oxidation, accelerating doxycycline metabolism, reduce its concentration in plasma. At simultaneous use of a metoksifluran the risk of development of fatal nephrotoxicity increases. Simultaneous use of Retinolum promotes increase in intracranial pressure.

Interaction with other medicines:

Absorption reduces a concomitant use of iron preparations, Natrii hydrocarbonas, aluminum, calcic or magnesian antacids, magniysoderzhashchy laxatives, Colestyraminum and a kolestipol. Barbiturates, carbamazepine, Phenytoinum, rifampicin — reduce concentration in plasma and reduce doxycycline T1/2 (induction of monooxygenases and acceleration of biotransformation) that can lead to decrease in antibacterial effect. At simultaneous use with bactericidal HP (including penicillin, cephalosporins) the effect decreases (simultaneous use should be avoided). Doxycycline reduces reliability of contraception and increases the frequency of "breakthrough" bleedings against the background of estrogensoderzhashchy oral contraceptives. Exponentiates effect of indirect anticoagulants.

Contraindications:

Hypersensitivity, porphyria, heavy liver failure, leukopenia, pregnancy (the II-III trimesters), the lactation period, children's age (up to 8 years - a possibility of formation of insoluble complexes with calcium and adjournment in a bone skeleton, enamel and dentine of teeth).
 
Use at pregnancy Pregnancy (the II-III trimesters), the lactation period.

Overdose:

Treatment: reception termination, symptomatic and maintenance therapy. The hemodialysis is inefficient.

Storage conditions:

List B. In the dry, protected from light place, at a temperature not above 25 °C. To store in the places unavailable to children. 
Period of validity 4 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Капс. 100 mg: 10 or 20 pieces.