Doxycycline Solution Tablets, 100 mg 10 pcs

Pharmacotherapeutic group: antibiotic – tetracycline

ATX code: J01AA02

Pharmacological action

Pharmacodynamics

A broad spectrum antibiotic of tetracycline group. It has bacteriostatic action, inhibits protein synthesis in microbial cell by interaction with 30S ribosome subunit. 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, Campylobacter fetus, Vibrio cholerae, 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).

As a rule, it has no effect on 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-over within the group (i.e., strains resistant to doxycycline will simultaneously be resistant to the entire tetracycline group).

Pharmacokinetics

Intake

Absorption is fast and high (about 100%). Food intake has little effect on absorption of the drug.

The maximum plasma concentration of doxycycline (2.6-3 mcg/ml) is reached 2 hours after 200 mg administration; after 24 hours the plasma concentration of the active substance decreases to 1.5 mcg/ml.

After administration of 200 mg on the first day of treatment and 100 mg daily thereafter, the plasma concentration of doxycycline is 1.5-3 mcg/ml.

Distribution

Doxycycline reversibly binds to plasma proteins (80-90%), penetrates well into organs and tissues, poorly – into cerebrospinal fluid (10-20% of plasma concentration), but doxycycline concentration in cerebrospinal fluid increases with inflammation of the spinal cord.

The volume of distribution is 1.58 l/kg. Within 30-45 minutes after oral administration doxycycline is found in therapeutic concentrations in the liver, kidneys, lungs, spleen, bones, teeth, prostate, eye tissues, pleural and ascitic fluid, bile, synovial exudate, exudate of maxillary and frontal sinuses and gingival sinus fluid.

In normal hepatic function, the concentration of doxycycline in bile is 5-10 times higher than in plasma.

In saliva, 5-27% of the value of doxycycline concentration in plasma is determined.

Doxycycline penetrates the placental barrier, in small amounts is secreted into breast milk. It accumulates in dentin and bone tissue.

Metabolism

Metabolizes a small part of doxycycline.

Elimation

The elimination half-life after a single oral dose is 16-18 hours, after repeated doses – 22-23 hours. Approximately 40% of doxycycline taken is excreted by kidneys and 20-40% is excreted in the intestines as inactive forms (chelates).

Pharmacokinetics in special clinical cases

The half-life of doxycycline in patients with impaired renal function does not change, as its excretion by the intestine increases. Hemodialysis and peritoneal dialysis have no effect on plasma concentration of doxycycline.

Indications

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 the 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 salpingoophoritis as part of combination therapy; including sexually transmitted infections: urogenital chlamydia, syphilis in patients with penicillin intolerance, uncomplicated gonorrhea (as an alternative therapy), granuloma inguinale, lymphogranuloma venereum,
infections of the gastrointestinal tract and biliary tract (cholera, yersiniosis, cholecystitis, cholangitis, gastroenterocolitis, bacillary and amoebic dysentery, traveler’s 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 localizations (including prostatitis and proctitis), rickettsiosis, Q fever, Rocky Mountain spotted fever, typhus (including typhus, tick-borne relapsing), Lyme disease (stage I – 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) to areas where strains resistant to chloroquine and/or pyrimethamine-sulfadoxine are common.

Pharmacological effect

Pharmacotherapeutic group: antibiotic – tetracycline

ATX code: J01AA02

Pharmacological action

Pharmacodynamics

Broad-spectrum antibiotic from the tetracycline group. It acts bacteriostatically, inhibits protein synthesis in the microbial cell by interacting with the 30S ribosomal subunit. 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., Campylobacter fetus, Vibrio cholerae, 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).

As a rule, it has no effect on Acinetobacter spp., Proteus spp., Pseudomonas spp., Serratia spp., Providencia spp., Enterococcus spp.

The possibility of acquired resistance to doxycycline in a number of pathogens, which is often cross-resistance within a group, should be taken into account (i.e., strains resistant to doxycycline will simultaneously be resistant to the entire group of tetracyclines).

Pharmacokinetics

Suction

Absorption is fast and high (about 100%). Food intake has little effect on the absorption of the drug.

The maximum concentration of doxycycline in blood plasma (2.6-3 mcg/ml) is achieved 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 mcg/ml.

Distribution

Doxycycline binds reversibly to plasma proteins (80-90%), penetrates well into organs and tissues, poorly into the cerebrospinal fluid (10-20% of the concentration in the blood plasma), however, the concentration of doxycycline in the cerebrospinal fluid increases with inflammation of the spinal membrane.

Volume of distribution – 1.58 l/kg. 30-45 minutes after oral administration, doxycycline 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 the maxillary and frontal sinuses, and in the fluid of the gingival grooves.

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 into breast milk in small quantities. Accumulates in dentin and bone tissue.

Metabolism

A small portion of doxycycline is metabolized.

Removal

The half-life after a single oral dose is 16-18 hours, after repeated doses it is 22-23 hours. Approximately 40% of doxycycline taken 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 does not change in patients with impaired renal function because its excretion by the intestines increases. Hemodialysis and peritoneal dialysis do not affect the concentration of doxycycline in blood plasma.

Special instructions

There is a possibility of cross-resistance and hypersensitivity with other tetracycline drugs.

Tetracyclines may increase prothrombin time; the use of tetracyclines in patients with coagulopathies should be carefully monitored.

The anti-anabolic 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 renal function. However, in patients with renal failure, an increase in azotemia may occur.

The use of tetracyclines in patients with impaired renal function requires medical supervision.

With long-term use of the drug, periodic monitoring of laboratory blood parameters, liver and kidney function is required.

Due to 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 while taking it and 2-3 weeks after stopping treatment, diarrhea caused by Clostridium difficile may develop. In mild cases, it is sufficient to discontinue treatment and use ion exchange resins (colestyramine, colestipol); in severe cases, replacement of loss of fluid, electrolytes and protein, and the appointment of vancomycin and metronidazole are indicated. You should not use medications that inhibit intestinal motility.

Long-term use of the drug can cause dysbacteriosis and, as a result, the development of hypovitaminosis (especially B vitamins).

To prevent dyspeptic symptoms, it is recommended to take the drug with meals.

To avoid the development of esophagitis or esophageal ulcers, it is necessary to take the drug with plenty of water and avoid using it immediately before bedtime.

Impact on the ability to drive vehicles and machinery

The effect on the ability to drive vehicles, machines and mechanisms is unknown.

In case of dizziness, blurred vision or double vision, driving vehicles or using machinery is not recommended (see “Side effects”).

Active ingredient

Doxycycline

Composition

For one 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; low-grade hyprolose – 29.25 mg; sodium saccharinate – 10.00 mg; hypromellose – 5.85 mg; magnesium stearate – 3.12 mg; colloidal silicon dioxide – 0.98 mg.

Pregnancy

Contraindicated during pregnancy (possible formation of insoluble complexes with calcium and deposition of doxycycline in the bone skeleton) and breastfeeding.

FDA category of effect on the fetus is D.

Contraindications

hypersensitivity to doxycycline, other tetracyclines or other components of the drug;
pregnancy;
breastfeeding period;
children under 8 years of age;
severe impairment of liver and/or kidney function;
porphyria;
lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Side Effects

From the gastrointestinal tract: anorexia, nausea, vomiting, dysphagia, diarrhea, anal itching, esophagitis, esophageal ulcer, dark coloration of the tongue. With long-term therapy, a deficiency of vitamins of the group may be observed due to the suppression of the growth of vitamin B-producing bacteria as part of the normal intestinal microflora.

Allergic reactions: exacerbation of systemic lupus erythematosus, syndrome similar to serum sickness, erythema multiforme, decreased blood pressure, tachycardia, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome).

From the skin: urticaria, photosensitivity, angioedema, anaphylactic reactions, maculopapular and erythematous rash, exfoliative dermatitis, Henoch-Schönlein purpura, photoonycholysis.

From the cardiovascular system: pericarditis.

From the liver: liver damage, sometimes associated with pancreatitis (with long-term use of the drug or in patients with renal or hepatic insufficiency), cholestasis.

From the kidneys: an increase in the concentration of residual urea nitrogen, due to the anti-anabolic effect of the drug, worsening azotemia in patients with renal failure. Consumption of products containing citric acid while taking doxycycline may cause symptoms similar to Fanconi syndrome: albuminuria, glycosuria, 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, papilledema), vestibular disorders (dizziness or unsteadiness), hallucinations, blurred vision, scotoma, double vision.

From the thyroid gland: in patients who have been receiving tetracycline antibiotics 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.

From the side of teeth and bones: doxycycline slows down osteogenesis, disrupts the normal development of teeth in children (the color of teeth irreversibly changes, enamel hypoplasia develops).

From the musculoskeletal system: arthralgia, myalgia.

Other: 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 interfere with cell wall synthesis (penicillins, cephalosporins), the effectiveness of the latter is reduced.

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 the blood plasma.

The simultaneous use of doxycycline and retinol increases intracranial pressure.

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, gastric lavage, drinking plenty of fluids, and, if necessary, inducing vomiting are recommended. Take activated carbon and osmotic laxatives. Hemodialysis and peritoneal dialysis are not recommended due to low efficiency.

Storage conditions

At a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf life

3 years. Do not use after expiration date.

Manufacturer

Ozon, Russia