Clinical and pharmacological group
Antibiotic of the tetracycline group
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.
Gram-positive microorganisms are highly sensitive to it: 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 (Bacillus anthracis), legionella (Legionella spp.), Brucella (Brucella spp.), Cholera vibrio (Vibrio cholera) , Rickettsia (Rickettsia spp.), glanders pathogens (Actinobacillus mallei), Chlamydia (psittacosis pathogens (Chlamydia psittaci), psittacosis (Rickettsiaformis psittacosi), trachoma (Chlamydia trachomatis ;, venereal granuloma (Calymmatobacterium granulomatis), malaria (Plasmodium falciparum), amoebic dysentery (Entamoeba histolytica).
It acts on most proteic strains, Pseudomonas aeruginosa and fungi.
To a lesser extent than other antibiotics of the tetracycline, it oppresses the intestinal flora, differs from them by a more complete absorption and longer duration of action. By the degree of antibacterial activity, doxycycline is superior to 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.
Absorption is fast and high (about 100%). The intake of food has no 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 administration of 200 mg the time to reach the maximum concentration in blood plasma is 2.5 hours, the maximum concentration in the blood plasma is 2.5 μg / ml, after 24 hours after the intake – 1.25 μg / ml.
The connection with plasma proteins is 80-93%. It penetrates well into organs and tissues; 30-45 minutes after ingestion is found in therapeutic concentrations in the liver, kidneys, lungs, spleen, bones, teeth, prostate gland, eye tissues, pleural and ascitic fluids, bile, synovial exudate, exudate of maxillary sinuses and frontal sinuses, in fluid 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 (basically 12-14 hours, on the 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. It is subjected to 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.
⊳Infectious-inflammatory❛ diseases caused by sensitive microorganisms: respiratory tract infections (pharyngitis, acute and chronic bronchitis, tracheitis, bronchopneumonia, lobar pneumonia, lung abscess, pleural empyema);
⊳infections❛ 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);
⊳infections❛ 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 eyes, syphilis, yawsinosis, legionellosis, rickettsiosis, chlamydia of various localizations (including prostatitis and proctitis), fever Koo, spotted fever of❛ the Rocky❛ Mountains, typhus (including mucous, tick-borne, recurrent) , Lyme disease (I v. – 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 trips (less than 4 months) in a territory where strains resistant to❛ chloroquine and / or pyrimethamine sulfadoxine are common;
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.
⇨hypersensitivity to doxycycline, drug components, other tetracyclines;
⇨deficiency of lactase;
⇨Severe hepatic impairment;
⇨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 teeth);
⇨Children aged after 12 years with a body weight of up to 45 kg.
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, one of the following regimens is prescribed: acute uncomplicated urethritis – a course dose of 500 mg (1 reception – 300 mg, subsequent 2 – 100 mg at 6-hour intervals) or 100 mg / day until complete cure (in women) or 100 mg 2 times 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 1-2 days before the trip, then daily during the trip and for 4 weeks 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 in this case a gradual accumulation of it in the body takes place (the risk of hepatotoxic action).
❂From the side of the nervous system: a 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 disorders: anorexia.
From the organs of hearing and the vestibular apparatus: ringing in the ears.
❂From the side 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 Staphylococcus strains ).
❂Allergic reactions: maculopapular rash, skin itching, 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 blood pressure, tachycardia, erythema multiforme.
❂From the hemopoiesis: hemolytic anemia, thrombocytopenia, neutropenia, leukopenia, eosinophilia, a decrease in the prothrombin index.
❂On the part of the hepatobiliary system: a violation of the liver, increased levels of hepatic transaminases, autoimmune hepatitis, cholestasis.
❂Musculoskeletal: arthralgia, myalgia.
❂Impaired renal and urinary tract function: Increased level of residual urea nitrogen.
❂Other: photosensitization, 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.
❃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.
Absorption is reduced by antacids containing salts of aluminum (Al3 +), calcium (Ca2 +) and magnesium (Mg2 +), iron preparations (Fe), sodium hydrogen carbonate, laxatives containing magnesium salts (Mg2 +), colestyramine and colestipol, therefore their use should be divided 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 stimulants 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.
To prevent locally irritating effect (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 a 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 have been receiving doxycycline for a long time, it is possible to dark brown staining of the tissue in micropreparations without disturbing its function.
In the experiment, it has been 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 in 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 cancel treatment and use ion-exchange resins (colestyramine, 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.
Impact on the ability to drive vehicles and manage mechanisms
Patients should refrain from all activities requiring increased attention, rapid mental and motor.
Pregnancy and lactemia
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 also cause fatty liver infiltration.
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.
Application in childhood
Contraindicated for children under 12 years of age (the possibility of formation of insoluble complexes with calcium ions (Ca2 +) with deposition in the bone skeleton, enamel and dentin of the teeth); and children aged after 12 years with a body weight of up to 45 kg.
Application is possible in children older than 12 years with a body weight of more than 45 kg according to the dosing regimen.
With violations of liver function
Contraindicated in severe hepatic insufficiency. In the presence of severe hepatic insufficiency, a decrease in the daily dose of doxycycline is required, since in this case a gradual accumulation of it in the body takes place (the risk of hepatotoxic action).
Terms and conditions of storage
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.
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