DOXYCYCLINE SOLUTION TABLETS

Compound

Per tablet: Active ingredient: doxycycline monohydrate - 104.00 mg, in terms of doxycycline - 100.00 mg. Excipients: lactose monohydrate (milk sugar) - 140.80 mg; microcrystalline cellulose - 96.00 mg; giprolose low-grade - 29.25 mg; sodium saccharinate - 10.00 mg; hypromellose - 5.85 mg; magnesium stearate - 3.12 mg; colloidal silicon dioxide - 0.98 mg.

Dosage form

dispersible tablets

Description

Oval, biconvex tablets, from gray-yellow or light yellow to brown-yellow color, interspersed, scored.

Pharmacodynamics

A broad-spectrum antibiotic from the tetracycline group. It acts bacteriostatically, inhibits protein synthesis in a microbial cell by interacting with the 30S subunit of ribosomes. Active against many gram-positive and gram-negative microorganisms: Streptococcus spp., Treponema spp., Staphylococcus spp., Klebsiella spp., Enterobacter spp. (including E. aerugenes), Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae, Chlamydia spp., Mycoplasma spp., Ureaplasma urealyticum, Listeria monocytogenes, Rickettsia spp, Typhus exanthematicus, Escherichia coli, Shigella spp. Yersinia spp. (including Yersinia pestis), Brucella spp., Francisella tularensis, Bacillus anthracis, Bartonella bacilliformis, Pasteurella multocida, Borrelia recurrentis, Clostridium spp. (except Clostridium difficile), Actinomyces spp., Fusobacterium fusiforme, Calymmatobacterium granulomatosis, Propionibacterium acnes, some protozoa (Entamoeba spp., Plasmodium falciparum). Generally not effective against Acinetobacter spp., Proteus spp., Pseudomonas spp., Serratia spp., Providencia spp., Enterococcus spp. The possibility of acquired resistance to doxycycline in a number of pathogens should be taken into account, which is often cross-group within a group (i.e. strains resistant to doxycycline will simultaneously be resistant to the entire group of tetracyclines).

Pharmacokinetics

Absorption Absorption is fast and high (about 100%). Eating slightly affects the absorption of the drug. The maximum concentration of doxycycline in plasma (2.6-3 μg / ml) is reached 2 hours after taking 200 mg; after 24 hours, the concentration of the active substance in the blood plasma decreases to 1.5 μg / ml. After taking 200 mg on the first day of treatment and 100 mg per day on subsequent days, the concentration of doxycycline in the blood plasma is 1.5-3 μg / ml. Distribution Doxycycline binds reversibly to plasma proteins (80-90%), penetrates well into organs and tissues, poorly into cerebrospinal fluid (10-20% of plasma concentration), however, the concentration of doxycycline in the cerebrospinal fluid increases with inflammation of the spinal membrane. The volume of distribution is 1.58 l/kg. 30-45 minutes after ingestion, doxycycline is found at therapeutic concentrations in the liver, kidneys, lungs, spleen, bones, teeth, prostate gland, eye tissues, in pleural and ascitic fluids, bile, synovial exudate, exudate of the maxillary and frontal sinuses, in gingival sulcus fluid. With normal liver function, the concentration of doxycycline in bile is 5-10 times higher than in plasma. In saliva, 5-27% of the concentration of doxycycline in blood plasma is determined. Doxycycline crosses the placental barrier and is secreted in small amounts into breast milk. Accumulates in dentin and bone tissue. Metabolism A small part of doxycycline is metabolized. Withdrawal The half-life after a single oral administration is 16-18 hours, after repeated doses - 22-23 hours. Approximately 40% of the taken doxycycline is excreted by the kidneys and 20-40% is excreted by the intestines in the form of inactive forms (chelates). Pharmacokinetics in special clinical situations The half-life of doxycycline in patients with impaired renal function does not change, because. its excretion by the intestine increases. Hemodialysis and peritoneal dialysis do not affect the concentration of doxycycline in plasma.

Indications for use

Infectious and inflammatory diseases caused by microorganisms sensitive to doxycycline: - respiratory tract infections, including pharyngitis, acute bronchitis, exacerbation of chronic obstructive pulmonary disease, tracheitis, bronchopneumonia, lobar pneumonia, community-acquired pneumonia, lung abscess, pleural empyema; - infections of ENT organs, including otitis media, sinusitis, tonsillitis; - infections of the genitourinary system: cystitis, pyelonephritis, bacterial prostatitis, urethritis, urethrocystitis, urogenital mycoplasmosis, acute orchiepididymitis; endometritis, endocervicitis and salpingo-oophoritis as part of combination therapy; including sexually transmitted infections: urogenital chlamydia, syphilis in patients with intolerance to penicillins, uncomplicated gonorrhea (as an alternative therapy), inguinal granuloma, venereal lymphogranuloma; - infections of the gastrointestinal tract and biliary tract (cholera, yersiniosis, cholecystitis, cholangitis, gastroenterocolitis, bacillary and amoebic dysentery, travelers' diarrhea); - infections of the skin and soft tissues (including wound infections after animal bites), severe acne (as part of combination therapy); - other diseases: yaws, legionellosis, chlamydia of various localization (including prostatitis and proctitis), rickettsiosis, Q fever, Rocky Mountain spotted fever, typhus (including typhus, tick-borne relapsing), Lyme disease (I stage - erythema migrans), tularemia, plague, actinomycosis, malaria; infectious eye diseases, as part of combination therapy - trachoma; leptospirosis, psittacosis, ornithosis, anthrax (including pulmonary form), bartonellosis, granulocytic ehrlichiosis; whooping cough, brucellosis, osteomyelitis; sepsis, subacute septic endocarditis, peritonitis; - prevention of postoperative purulent complications; malaria caused by Plasmodium falciparum during short-term travel (less than 4 months) in areas where strains resistant to chloroquine and / or pyrimethamine-sulfadoxine are common.

Contraindications

Hypersensitivity to doxycycline, other tetracyclines or other components of the drug; - pregnancy; - the period of breastfeeding; - children's age up to 8 years; - severe violations of the liver and / or kidneys; - porphyria; - lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Use during pregnancy and lactation

Doxycycline crosses the hemato-placental barrier. Tetracyclines have an adverse effect on the fetus (deceleration of osteogenesis) and on the formation of tooth enamel (irreversible discoloration, hypoplasia). In view of this, as well as the increased risk of liver damage in the mother, tetracyclines are not used during pregnancy, unless the drug is the only remedy for the treatment or prevention of especially dangerous and severe infections (Rocky Mountain spotted fever, inhalation exposure to Bacillus anthracis, etc.). Before prescribing doxycycline to women of childbearing age, pregnancy should first be excluded. Doxycycline passes into breast milk. Due to adverse effects on the fetus, doxycycline, like other tetracyclines, is not used during breastfeeding. If the appointment of tetracyclines is necessary, breastfeeding is stopped.

Side effects

From the gastrointestinal tract: anorexia, nausea, vomiting, dysphagia, diarrhea, anal itching, esophagitis, esophageal ulcer, dark staining of the tongue. With prolonged therapy, there may be a deficiency of B vitamins due to the suppression of the growth of vitamin B-producing bacteria in the normal intestinal microflora. Allergic reactions: exacerbation of systemic lupus erythematosus, a syndrome similar to serum sickness, erythema multiforme, lowering blood pressure, tachycardia, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome). On the part of the skin: urticaria, photosensitivity, angioedema, anaphylactic reactions, maculopapular and erythematous rash, exfoliative dermatitis, Henoch-Schonlein purpura, photoonycholysis. From the side of the cardiovascular system: pericarditis. On the part of the liver: liver damage, sometimes associated with pancreatitis (with prolonged use of the drug or in patients with renal or hepatic insufficiency), cholestasis. From the side of the kidneys: an increase in the concentration of residual urea nitrogen due to the antianabolic effect of the drug, exacerbation of azotemia in patients with renal insufficiency. Consumption of products containing citric acid while taking doxycycline may cause symptoms similar to Fanconi's syndrome: albuminuria, glucosuria, hypophosphatemia, hypokalemia, and renal tubular acidosis. From the hematopoietic system: hemolytic anemia, thrombocytopenia, neutropenia, eosinophilia, decreased prothrombin activity. From the nervous system: benign increase in intracranial pressure (anorexia, vomiting, headache, tinnitus, tremor, swelling of the optic nerve), vestibular disorders (dizziness or unsteadiness), hallucinations, blurred vision, scotoma, double vision. From the side of the thyroid gland: in patients who have been receiving antibiotics from the tetracycline group for a long time, reversible dark brown staining of the thyroid tissue is possible, in most cases not accompanied by a violation of its function. On the part of teeth and bones: doxycycline slows down osteogenesis, disrupts the normal development of teeth in children (the color of the teeth changes irreversibly, enamel hypoplasia develops). From the musculoskeletal system: arthralgia, myalgia. Others: candidiasis, glossitis, staphylococcal enterocolitis, pseudomembranous colitis, anogenital candidiasis, stomatitis, vaginitis.

Interaction

Antacids containing aluminum, magnesium, calcium, iron preparations, sodium bicarbonate, magnesium-containing laxatives reduce the absorption of doxycycline, so their use should be separated by an interval of 3 hours. Due to the suppression of intestinal microflora by doxycycline, the prothrombin index decreases, which requires dose adjustment of indirect anticoagulants. When doxycycline is combined with bactericidal antibiotics that disrupt the synthesis of the cell wall (penicillins, cephalosporins), the effectiveness of the latter decreases. Doxycycline reduces the reliability of contraception and increases the frequency of acyclic bleeding when taking estrogen-containing hormonal contraceptives. Ethanol, barbiturates, rifampicin, carbamazepine, phenytoin and other stimulants of microsomal oxidation, accelerating the metabolism of doxycycline, reduce its concentration in blood plasma. The simultaneous use of doxycycline and retinol increases intracranial pressure.

Dosage and administration

inside. The tablets are dissolved in a small amount of water (about 20 ml) to obtain a suspension, the tablets can also be swallowed whole, divided into parts or chewed with water. Preferably taken with food. Take the pills while sitting or standing, which reduces the chance of developing esophagitis or an esophageal ulcer. The drug should not be taken immediately before bedtime. Usually the duration of treatment is 5-10 days. Adults and children over 8 years of age weighing more than 50 kg 200 mg in 1-2 doses on the first day of treatment, then 100 mg daily. In cases of severe infections, the drug is prescribed at a dose of 200 mg daily during the entire course of treatment. Children 8-12 years old weighing less than 50 kg The average daily dose is 4 mg / kg on the first day, then 2 mg / kg per day (in 1-2 doses). In cases of severe infection, the drug is used at a dose of 4 mg / kg daily during the entire course of treatment. Features of dosing for certain diseases In case of infection caused by S.pyogenes, the drug is taken for at least 10 days. For uncomplicated gonorrhea (with the exception of anorectal infections in men): Adults - 100 mg 2 times a day until complete recovery (on average within 7 days), or 600 mg is prescribed for one day - 300 mg in 2 doses (second intake 1 hour after the first). For primary syphilis - 100 mg 2 times a day for 14 days, for secondary syphilis - 100 mg 2 times a day for 28 days. With uncomplicated urogenital infections caused by Chlamydia trachomatis, cervicitis, non-gonococcal urethritis caused by Ureaplasma urealiticum - 100 mg 2 times a day for 7 days. With acne - 100 mg 1 time per day, the course of treatment is 6-12 weeks. Malaria (prevention): 100 mg once a day for 2 days before the trip, then daily during the trip and within 4 weeks after returning; children over 8 years old - 2 mg / kg 1 time per day. Diarrhea "travelers" (prevention) - 200 mg on the first day of the trip in 1 or 2 doses, then 100 mg 1 time per 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; prevention of leptospirosis - 200 mg once a week during a stay in a disadvantaged area and 200 mg at the end of the trip. In order to prevent infections during medical abortion - 100 mg 1 hour before and 200 mg after the intervention. The maximum daily dose for adults is up to 300 mg / day or up to 600 mg / day for 5 days in severe gonococcal infections. For children over 8 years old weighing more than 50 kg - up to 200 mg, for children 8-12 years old weighing less than 50 kg - 4 mg / kg daily during the entire treatment. In the presence of renal insufficiency (creatinine clearance less than 60 ml / min) and / or liver failure, a decrease in the daily dose of doxycycline is required, since in this case it gradually accumulates in the body (risk of hepatotoxicity).

Overdose

Symptoms Increased dose-dependent adverse reactions caused by liver damage - vomiting, fever, jaundice, azotemia, increased transaminase activity, increased prothrombin time. Treatment Immediately after taking large doses, it is recommended to wash the stomach, drink plenty of fluids, and, if necessary, induce vomiting. Take activated charcoal and osmotic laxatives. Hemodialysis and peritoneal dialysis are not recommended due to low efficiency.

special instructions

There is a possibility of cross-resistance and hypersensitivity with other tetracycline drugs. Tetracyclines may increase prothrombin time, and the use of tetracyclines in patients with coagulopathy should be carefully monitored. The antianabolic effect of tetracyclines can lead to an increase in the concentration of residual urea nitrogen in the blood. As a rule, this is not significant for patients with normal kidney function. However, in patients with renal insufficiency, there may be an increase in azotemia. The use of tetracyclines in patients with impaired renal function requires medical supervision. With prolonged use of the drug, periodic monitoring of laboratory blood parameters, liver and kidney function is required. In connection with the possible development of photodermatitis, it is necessary to limit insolation during treatment and for 4-5 days after it. When using the drug, both against the background of taking it and 2-3 weeks after stopping treatment, it is possible to develop diarrhea caused by Clostridium difficile. In mild cases, it is sufficient to cancel treatment and use ion-exchange resins (colestiramine, colestipol), in severe cases, compensation for the loss of fluid, electrolytes and protein, and the appointment of vancomycin are indicated. metronidazole. Do not use drugs that inhibit intestinal motility. Prolonged use of the drug can cause dysbacteriosis and, as a result, the development of hypovitaminosis (especially B vitamins). To prevent dyspeptic phenomena, it is recommended to take the drug during meals. To avoid the development of esophagitis or ulcers of the esophagus, it is necessary to take the drug with plenty of water and avoid use immediately before bedtime.

Influence on the ability to drive vehicles and control mechanisms

The effect on the ability to drive vehicles, machines and mechanisms is unknown. In case of development of dizziness, blurred vision or double vision, driving vehicles or mechanisms is not recommended (see "Side Effects").