Doxycycline - instructions for use, dose, side effects, contraindications

Composition:Each capsule contains: active substance: doxycycline hiclate (in terms of doxycycline) - 100 mg; auxiliary substances: calcium stearate - 1,7 mg, lactose monohydrate - 220 mg, potato starch - up to 340 mg; the composition of the capsule: gelatin - 61,624 mg, glycerol - 0,193 mg, water purified - 10,585 mg, titanium dioxide - 0,497 mg, sodium lauryl sulfate - 0.049 mg, dye sunset yellow E-110 0.01 mg, quinoline yellow color E-104 0.042 mg.

Description:Capsules hard gelatinous, yellow, cylindrical with hemispherical ends.The contents of the capsules are a yellow powder with white impregnations. It is allowed to have capsule-shaped seals in the form of a column or a tablet, which, when pressed with a glass rod, crumble.

Pharmacotherapeutic group:Antibiotic, tetracycline

ATX: & nbsp

J.01.A.A.02 Doxycycline

Pharmacodynamics:

Semisynthetic tetracycline, bacteriostatic broad-spectrum antibiotic. Penetrating into the cell, acts on intracellularly located pathogens. Suppresses the synthesis of proteins in a microbial cell, disrupts the binding of the transport aminoacyl RNA to the 30S subunit of the ribosomal membrane. TO

It is highly sensitive: gram-positive microorganisms Staphylococcus spp. (including Staphylococcus aureus, Staphylococcus epidermidis), Streptococcus spp. (including Streptococcus pneumoniae), Clostridium spp., Listeria spp .; Actinomyces israeli; and Gram-negative microorganisms: Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae, Klebsiella spp., Escherichia coli, Shigella spp., Enterobacter, Salmonella spp., Bordetella pertussis, Bacteroides spp., Treponema spp. (including strains resistant to other antibiotics, such as modern penicillins and cephalosporins). The most sensitive are Haemophilus influenzae (91-96%) and intracellular pathogens. Doxycycline is active against most pathogens of dangerous infectious diseases: plague (Yersinia spp.), tularemia (Francisella tularensis),anthrax anthracis, legionella (Legionella spp.), brucella (Brucella spp.), cholera vibrio (Vibrio cholera), rickettsia (Rickettsia spp.), causative agents of sapa (Actinobacillus mallei), chlamydia (causative agents of ornithosis (Chlamydia psittaci) , psittacosis (Rickettsiaformis psittacosi), trachoma (Chlamydia trachomatis ;, venereal granuloma (Calymmatobacterium granulomatis), malaria (Plasmodium falciparum), amoebic dysentery (Entamoeba histolytica) .It does not affect most strains of Proteus, Pseudomonas aeruginosa and fungi. other antibiotics of the tetracycline series, depresses the intestinal flora, differs from them more complete suction and longer duration of action. According to the degree of antibacterial activity doxycycline surpasses natural tetracyclines. In contrast to tetracycline and oxytetracycline, it has higher therapeutic efficacy, which is manifested by treatment in 10 times smaller doses, and a longer action. There is cross-resistance to other tetracyclines, as well as to penicillins.

Pharmacokinetics:Absorption is fast and high (about 100%). Eating does not have a significant effect on the degree of absorption. Has a high degree of solubility in lipids and a low affinity for the binding of calcium ions (Ca2 +).After oral intake of 200 mg, the time to reach the maximum concentration in the blood plasma is 2.5 hours, the maximum concentration in the blood plasma is 2.5 μg / ml, and after 24 hours after administration, 1.25 μg / ml. The connection with plasma proteins is 80-93%. It penetrates well into organs and tissues; 30-45 minutes after oral administration at therapeutic concentrations detected in the liver, kidney, lung, spleen, bones, teeth, prostate, eye tissues, pleural and ascitic fluids, bile, synovial exudate, the exudate maxillary and frontal sinuses, in the liquid gingival sulci. Poor penetration into the cerebrospinal fluid (10-20% of the plasma level). Penetrates through the placental barrier, is determined in human milk. The volume of distribution is 0.7 l / kg. Metabolised in the liver 30-60%. The half-life is 10-16 hours (mainly 12-14 hours, on average 16.3 hours). With repeated administration, the drug can accumulate. It accumulates in the reticulo-endothelial system and bone tissue. In bones and teeth, it forms insoluble complexes with calcium ions (Ca2 +). It is excreted with bile, where it is found in high concentration. Undergoes intestinal-hepatic recirculation, is excreted by the intestine (20-60%); 40% of the dose is given by the kidneys for 72 hours (of which 20-50% is unchanged), in severe chronic renal failure, only 1-5%.In patients with impaired renal function or azotemia, gastrointestinal secretion is an important way of excretion.

Indications:

Infectious-inflammatory diseases caused by sensitive microorganisms: respiratory tract infections (pharyngitis, acute and chronic bronchitis, tracheitis, bronchopneumonia, lobar pneumonia, lung abscess, pleural empyema);

infection of the ENT organs (otitis media, tonsillitis, sinusitis, etc.);

infections of the genitourinary system (cystitis, pyelonephritis, prostatitis, urethritis, urethrocystitis, urogenital mycoplasmosis, endometritis, endocervicitis, acute orchypididitis, gonorrhea);

infection of the biliary tract and gastrointestinal tract (cholecystitis, cholangitis, gastroenterocolitis, bacterial dysentery, traveler's diarrhea); infections of the skin and soft tissues (phlegmon, abscess, furunculosis, panaritium, infected burns, wounds, etc.);

infectious diseases of the eye, syphilis, yawsinosis, legionellosis, rickettsiosis, chlamydia of various localization (including prostatitis and proctitis), fever Ky, spotty fever of the Rocky Mountains, typhus (including fungal, tick-borne recurrent), disease Lyme (I st.- erythema migrans), 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; malaria caused by Plasmodium falciparum, during short travel (less than 4 months) in the area where common strains resistant to chloroquine and / or pyrimethamine-sulfadoxine.

As a preparation of the "first" series, patients under 65 years of age are exacerbated with exacerbation of chronic bronchitis (including bronchial asthma) without concomitant diseases (these exacerbations are often caused by Haemophilus influenzae). Effective with exacerbation of bronchopulmonary infection (usually staphylococcal etiology) in patients with cystic fibrosis, chlamydial arthritis, granulocyte erlichiosis. In elderly patients it is used to treat acute prostatitis and urinary infection caused by Escherichia coli.

Contraindications:Hypersensitivity to doxycycline, drug components, other tetracyclines; deficiency of lactase, lactose intolerance,glucose-galactose malabsorption, porphyria, severe hepatic insufficiency, leukopenia, children's age (up to 12 years - the possibility of formation of insoluble complexes with calcium ions (Ca2 +) with deposition in the bone skeleton, enamel and dentin) and children after 12 years with weight body up to 45 kg.

Pregnancy and lactation:

The use of the drug during pregnancy is contraindicated, because, penetrating the placenta, the drug can disrupt the normal development of the teeth, inhibit the growth of the bones of the fetal skeleton, and cause fatty infiltration of the liver.

During the lactation period, the use of doxycycline is contraindicated. In case of need of application of a preparation, for the period of treatment feeding by a breast should be stopped.

Dosing and Administration:

Inside, in adults and children over 12 years with a body weight of more than 45 kg, the average daily dose is 200 mg on the first day (divided into 2 divided doses - 100 mg twice a day), then 100 mg / day.

In chronic infections of the urinary system - 200 mg / day throughout the period of therapy.

In the treatment of gonorrhea prescribed for one of the following schemes: acute uncomplicated urethritis - course dose of 500 mg (1 reception - 300 mg,the subsequent 2 - 100 mg at 6-hour intervals) or 100 mg / day until complete cure (in women) or 100 mg twice a day for 7 days (in men); with complicated forms of gonorrhea, the course dose is 800-900 mg, which is divided into 6-7 receptions (300 mg - 1 reception, then at an interval of 6 hours for 5-6 follow-up).

In the treatment of syphilis - 300 mg / day for at least 10 days.

In uncomplicated infections of the urethra, cervix and rectum caused by Chlamydia trachomatis, 100 mg are prescribed twice a day for at least 7 days.

Infections of male genital organs - 100 mg twice a day for 4 weeks.

Treatment of malaria resistant to chloroquine - 200 mg / day for 7 days (in combination with shizontocidal drugs - quinine); malaria prophylaxis - 100 mg once a day for 1 -2 days before the trip, then daily during the trip and during

4 ned after return;

Diarrhea "travelers" (prevention) - 200 mg on the first day of the trip (for 1 dose or 100 mg twice a day), 100 mg once a day during the entire stay in the region (no more than 3 weeks).

Treatment of leptospirosis - 100 mg orally 2 times a day for 7 days; prophylaxis of leptospirosis - 200 mg once a week during a stay in a dysfunctional area and 200 mg at the end of the trip.

Prevention of infections after medical abortion - 100 mg for 1 hour before abortion and 200 mg - 30 minutes after.

With acne - 100 mg / day, the course - 6-12 weeks.

Maximum daily doses for adults - up to 300 mg / day or 600 mg / day for 5 days with severe gonococcal infections.

In the presence of severe hepatic insufficiency, a decrease in the daily dose of doxycycline is required, since this gradually accumulates in the body (the risk of hepatotoxic action).

Side effects:

From the nervous system:

benign increase in intracranial pressure (decreased appetite, vomiting, headache, edema of the optic nerve disc), toxic effects on the central nervous system (dizziness or instability),

Metabolic disease:

anorexia.

From the organs of hearing and the vestibular apparatus:

tinnitus.

On the part of the organs of vision:

blurred vision, scotoma and diplopia as a result of increased intracranial pressure.

From the digestive system:

nausea, constipation or diarrhea, abdominal pain, glossitis, dysphagia, esophagitis (including erosive), gastritis, ulceration of the stomach and duodenum, pseudomembranous colitis, enterocolitis (due to the proliferation of resistant strains of staphylococci).

Allergic reactions:

maculopapular rash, skin itch, skin hyperemia, angioedema, anaphylactoid reactions, drug lupus erythematosus, erythematous rash, exfoliative dermatitis, urticaria, anaphylaxis, anaphylactic shock, anaphylactoid reactions, Stevens-Johnson syndrome.

From the cardiovascular system:

pericarditis, lowering of arterial pressure, tachycardia, erythema multiforme.

From the hematopoiesis:

hemolytic anemia, thrombocytopenia, neutropenia, leukopenia, eosinophilia, a decrease in the prothrombin index.

From the hepatobyas system:

impaired liver function, increased levels of hepatic transaminases, autoimmune hepatitis, cholestasis.

Musculoskeletal system:

arthralgia, myalgia.

Impaired renal and urinary tract function:

increase in the level of residual urea nitrogen.

Other:

photosensitivity, superinfection; stable change in the color of tooth enamel, inflammation in the anogenital zone. Candidiasis (vaginitis, glossitis, stomatitis, proctitis), dysbacteriosis, a syndrome similar to serum sickness, toxic epidermal necrolysis.

Overdose:

Symptoms: with the introduction of high doses, especially in patients with impaired liver function, neurotoxic reactions may appear: dizziness, nausea, vomiting, convulsions, impaired consciousness due to increased intracranial pressure.

Treatment: drug withdrawal, gastric lavage with activated charcoal, symptomatic therapy, inside appoint antacids and magnesium sulfate to prevent the absorption of doxycycline. There is no specific antidote. Hemodialysis and peritoneal dialysis are ineffective.

Interaction:

Absorption is reduced by antacids containing aluminum salts (A1³⁺ ), calcium (Ca²⁺) and magnesium (Mg²⁺), iron (Fe) preparations, sodium hydrogen carbonate, laxatives containing magnesium salts (Mg²⁺), colestramine and colestipol, so their use should be separated by an interval of 3 hours.

In connection with the suppression of the intestinal microflora reduces the prothrombin index, which requires correction of the dose of indirect anticoagulants.

When combined with bactericidal antibiotics that disrupt the synthesis of the cell wall (penicillins, cephalosporins), the effectiveness of the latter is reduced.

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 stimulators of microsomal oxidation, accelerating the metabolism of doxycycline, reduce its concentration in the plasma.

With simultaneous use with methoxyflurane, it is possible to develop acute renal failure, up to a lethal outcome.

Simultaneous use of retinol helps increase intracranial pressure.

Special instructions:

To prevent locally irritating effects (esophagitis, gastritis, ulceration of the mucous membrane of the gastrointestinal tract) it is recommended to take in the daytime hours with a lot of liquid, food. In connection with the possible development of photosensitization, it is necessary to limit the insolation during treatment and for 4-5 days after it. With prolonged use, periodic monitoring of liver function, hematopoiesis is necessary. May mask the manifestations of syphilis, in connection with which, with the possibility of mixed infection, a monthly serological analysis is necessary for 4 months.All tetracyclines form stable complexes with calcium ions (Ca²⁺) in any bone-forming tissue. In this regard, reception during the development of teeth can cause long-term staining of teeth in yellow-gray-brown color, as well as hypoplasia of the enamel. 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 received long-term doxycycline, it is possible to dark brown staining of tissue in micropreparations without disturbing its function.

In the experiment it was established that doxycycline can exert a toxic effect on the development of the fetus (delay in the development of the skeleton) - blocks metalloproteases (enzymes that catalyze the degradation of collagen and proteoglycans) in the cartilage, leading to a reduction in lesions with deforming osteoarthritis. When the dose is increased above 4 g, the pharmacokinetics of doxycycline does not depend on the dose and the concentration in the blood does not increase.

When using the drug, both on the background of taking and 2-3 weeks after stopping treatment, it is possible to develop diarrhea caused by Clostridium difficile. In light cases, it is sufficient to discontinue treatment and apply ion-exchange resins (colestramine, colestipol), in severe cases, compensation for loss of fluid, electrolytes and protein, the appointment of vancomycin, bacitracin or metronidazole. Do not use drugs that inhibit the intestinal motility.

Effect on the ability to drive transp. cf. and fur:Patients should refrain from all activities requiring increased attention, rapid mental and motor reaction.

Form release / dosage:

Capsules 100 mg.

Packaging:

10 capsules per contour cell packaging made of polyvinylchloride film and aluminum foil. One or two contour packs, together with instructions for use, are placed in a pack of cardboard.

Packaging for hospitals: 150 contour packs with equal number of instructions for use are swept into a cardboard box.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-000756

Date of registration:07.05.2010 / 10.02.2015

The owner of the registration certificate:BELMEDPREPARATY, RUP BELMEDPREPARATY, RUP Republic of Belarus

Manufacturer: & nbsp

BELMEDPREPARATY, RUP Republic of Belarus

Information update date: & nbsp10.02.2016

Illustrated instructions

Instructions

Doxycycline (Doxycycline)