Doxycycline

General characteristics. Structure:

Active ingredient: 100 mg of doxycycline (in the form of doxycycline of a hiklat) in 1 capsule.

Excipients: lactose monohydrate, potato starch, magnesium stearate. Structure of the capsule: gelatin, glycerin, methylparahydroxybenzoate, пропилпарагидроксибензоат, sodium lauryl sulfate, yellow quinolinic E 104, yellow sunset E 110.

Pharmacological properties:

Pharmacodynamics. Semi-synthetic antibiotic of group of tetracyclines of a broad spectrum of activity. Works bacteriostatically, oppressing synthesis of protein at microorganisms.

The mechanism of action is connected with disturbance of protein synthesis in cells of bacteria. Doxycycline gets in a bacterial cell and interacts with the aminoacylic center of 50S-subunit of ribosomes. Breaks peptidiltranslokazny reaction, without allowing to deliver aminoacyl-TRNK new amino acids in a ribosome for creation of a proteinaceous chain. On ribosomes of the person does not make impact that is connected with existence of ribosome 70S-subunit at it instead of 50S-subunit.

It is active concerning gram-positive aerobic bacteria: Streptococcus haemolyticus, Streptococcus viridans, Streptococcus pneumoniae, Enterococcus faecalis, Staphylococcus spp. (including Staphylococcus aureus, Staphylococcus epidermidis), Listeria spp. (including Listeria monocytogenes), Bacillus anthracis; gram-negative aerobic bacteria: Neisseria gonorrhoeae, Neisseria meningitides, Haemophilus influenzae, Brucella spp., Escherichia coli, Shigella spp., Salmonella spp., Yersinia spp., Pasteurella spp., Vibrio spp., Francisella tularensis, Klebsiella spp., Legionella spp., Treponema spp. (including strains steady against β-laktamny antibiotics), Campylobacter spp., Rickettsiae spp.; gram-negative anaerobic microorganisms: Clostridium spp., Enterobacter spp., Bacteroides spp.

It is highly active concerning Mycoplasma spp., Chlamydia spp. Affects some protozoa: P. falciparum, Entamoeba histolytica. The majority of strains of Proteus spp are steady against doxycycline., Serratia spp., Pseudomonas spp., fungi (except for Actynomyces spp.). Bacteria steady against tetracycline have cross doxycycline resistance.

Doxycycline is capable to block metalproteinases of a matrix of connecting fabric (the enzymes destroying collagen and proteoglycans) and to reduce expressiveness of injuries of a cartilage at the deforming osteoarthrosis.

Pharmacokinetics. After introduction it is inside soaked up quickly and almost completely. Bioavailability makes 97 – 98%. Meal has no significant effect on absorption. After intake in a dose of 200 mg the maximum concentration (Cmax) makes 2,5 – 2,7 mkg/ml and is reached in 2,0 – 2,5 h. In 24 h after reception concentration of doxycycline makes 1,25 – 1,5 mkg/ml. Therapeutic concentration of doxycycline in plasma makes 1,5 – 3,0 mkg/ml.

In blood reversibly contacts proteins of plasma (for 80-93%). Easily gets through gistogematichesky barriers into all bodies and fabrics. In 30-45 min. after reception it is found in therapeutic concentration in a liver, kidneys, lungs, a spleen, bones, teeth, a prostate gland, tissues of an eye, pleural and peritoneal liquid, bile, synovial fluid, exudate of Highmore's and frontal sinuses. Collects in fabrics of reticuloendothelial system and bones where forms insoluble complexes with Ca2+ ions. Gets through a placental barrier, it is allocated in breast milk (30-40% of its level in plasma). In saliva concentration of doxycycline makes 5-27% of its concentration in a blood plasma. Through a blood-brain barrier gets badly. Doxycycline level in cerebrospinal fluid makes 10-20% of level in plasma. Doxycycline distribution volume – 0,7 l/kg. At repeated introductions doxycycline can kumulirovat.

Metabolism of a doksitsilin proceeds in a liver where 30-60% of medicine are exposed to biotransformation. It is removed with bile (20 – 60%) and comes to excrements where forms inactive chelate complexes. Is exposed to enterogepatichesky circulation. It is to a lesser extent removed with urine (40% in 72 hours, in the form of active doxycycline). The period of semi-elimination of doxycycline makes 10 – 18 h after a single dose and increases to 22 – 23 h at reception of repeated doses. At patients with a renal failure elimination of doxycycline does not change since removal of doxycycline through intestines kompensatorno increases.

Indications to use:

* infections of upper and lower parts of respiratory tracts and ENT organs (an exacerbation of chronic bronchitis at persons up to 65 years, without the accompanying pathology; pneumonia, otitises, sinusitis);

* urogenital infections (pyelonephritis, an urethritis, prostatitis, orkhiepididimit, a cervicitis, an endometritis);

* mycoplasmal and Chlamidia infections, including syndrome of Reuters;

* gonorrhea, primary and secondary syphilis at patients with an allergy to β-laktamny antibiotics;

* infections of biliary tract (cholecystitis, cholangitis);

* intestinal infections (gastroenterocolitis, diarrhea of travelers, иерсиниоз, shigellosis);

* infections of skin and soft tissues (phlegmons, abscesses, furunculosis, acne rash);

* the infected burns and wounds;

* legionellosis;

* the rickettsioses or other infections caused by the rickettsiae sensitive to doxycycline;

* Lyme's disease (tick-borne borreliosis);

* especially dangerous infections: plague, tularemia, malignant anthrax, сап, brucellosis, cholera;

* actinomycosis;

* malaria (treatment and prevention);

* amoebic dysentery;

* a hay fever, granulotsitarny эрлихоз, osteomyelitis as a part of a combination therapy;

* prevention of an infection at medical abortion.

Route of administration and doses:

Medicine is applied inside in time or after food, washing down with a glass of water.

To adults and children 12 years with body weight are more senior more than 45 kg appoint in the first day 200 mg (2 capsules) in 1 or 2 receptions, from the second day on 100 mg (1 capsule) once a day. The maximum daily dose at heavy infections of 200 mg/days in 1 – 2 reception.

Duration of treatment depends on a type of an infection and makes usually 5 – 10 days. At Lyme's disease a course of treatment 3 - 4 weeks, at a brucellosis – 1,5 – 6 months.

At treatment of gonorrhea appoint to women on 200 mg/days (2 capsules) in 1 reception, to men on 200 – 300 mg/days (2 – 3 capsules) in 1 reception within 5 days.

At syphilis appoint in a dose 300 mg/days (3 capsules) within 10 days.

At treatment of a chlamydial and mycoplasmal infection on 200 mg/days (2 capsules) within 7 days.

At treatment of acne rash on 50 mg/days within 6 – 12 weeks.

For prevention of infections at medical abortion appoint twice – 100 mg (1 capsule) in 1 hour prior to an abortation and 200 mg (2 capsules) in 30 min. after it.

Decrease in a daily dose is required from patients with a liver failure.

Features of use:

Pregnancy. In experiments on animals it was shown that doxycycline causes a skeleton arrest of development in a fruit. Its use during pregnancy is contraindicated.

Lactation period. Due to the intake of doxycycline in mother's milk, for the period of treatment stop breastfeeding.

Use in pediatrics. It is not recommended to apply at children up to 12 years as doxycycline can lead at them to disturbance of formation of a skeleton, teeth, to cause a hypoplasia and an irreversible prokrashivaniye of enamel of teeth in yellow-gray-brown color.

At children 12 years with body weight to 45 kg are more senior medicine needs to be applied in other dosage form.

Care at use. Due to the possible development of a photosensitization it is necessary to limit insolation for the period of treatment and within 4 - 5 days after it. For the prevention of development of an erosive canker of a gullet it is recommended to wash down doxycycline with a large amount (200 – 300 ml) of water.

In need of long administration of doxycycline follows periodically (at least 1 time in 5-7 days) to control indicators of peripheral blood, function of a liver.

Influence on laboratory indicators. At treatment false positive results when determining level of catecholamines in urine by a fluorescent method can arise doxycycline. At a research of bioptat of a thyroid gland at persons it is long receiving doxycycline their brown prokrashivaniye is possible that does not testify to pathology.

Side effects:

* increase in intracranial pressure (anorexia, nausea, vomiting, headache, papilledema), dizziness, ataxy.

* nausea, diarrhea, lock, glossitis, dysphagy, esophagitis (including erosive and ulcer), gastritis, stomach ulcers and duodenum, coloenteritis.

* allergic reactions, skin rashes, itch, dermahemia, Quincke's disease, anaphylactoid reactions, lupoid syndrome.

* photosensitization.

* hemolitic anemia, thrombocytopenia, neutropenia, eosinophilia.

* intersticial nephrite, nephropathy.

* steady discoloration of an adamantine substance of tooth.

* an inflammation in the field of an anogenitalny zone.

* dysbacteriosis, superinfections (candidiasis).

Interaction with other medicines:

Antiacid means on the basis of magnesium, aluminum and calcium cause decrease in absorption of doxycycline due to education with it chelate complexes. The interval between reception of antacids and doxycycline has to be not less than 3 hours.

Iron preparations cause decrease in absorption of doxycycline due to education with it chelate complexes.

Purgatives on the basis of salts of magnesium cause decrease in absorption of doxycycline due to education with it chelate complexes.

Doxycycline strengthens effect of indirect anticoagulants due to suppression of an indestinal flora and decrease in synthesis of vitamin K.

Doxycycline reduces efficiency of estrogensoderzhashchy oral contraceptives and increases the development frequency of "break bleedings".

The medicines inducing microsomal enzymes of a liver (barbiturates, Phenytoinum, carbamazepine, rifampicin) strengthen metabolism of doxycycline and reduce its concentration in blood.

β-laktamny antibiotics and doxycycline mutually weaken antimicrobic action of each other.

Colestyraminum and колестипол reduce absorption of doxycycline in intestines.

Retinolum strengthens neurotoxic effect of doxycycline and increases probability of development of intracranial hypertensia.

Doxycycline can increase plasma concentration of cyclosporine, Joint purpose of these medicines has to be carried out only under medical control.

Combined use of tetracyclines and metoksifluran (means for an inhalation anesthesia) can lead to development of a heavy renal failure (including lethal outcomes).

Milk reduces degree and speed of absorption of doxycycline. Regular alcohol intake increases the period of semi-elimination of doxycycline and slows down its removal.

Contraindications:

* hypersensitivity to doxycycline and other tetracyclines;

* children's age up to 12 years;

* children aged after 12 years with body weight to 45 kg;

* pregnancy and lactation;

* leukopenia;

* porphyria;

* heavy abnormal liver functions and kidneys.

Overdose:

Symptoms: at introduction of high doses, especially at patients with an abnormal liver function emergence of neurotoxic reactions is possible: dizzinesses, nausea, vomitings, spasms, disturbance of consciousness owing to increase in intracranial pressure.

Treatment: medicine cancellation, a gastric lavage with absorbent carbon, symptomatic therapy, inside appoint antacids and magnesium sulfate for prevention of absorption of doxycycline. The specific antidote does not exist. The hemodialysis and peritoneal dialysis are inefficient.

Storage conditions:

In the place protected from light and moisture, at a temperature not over 25 ºС. To store in the place, unavailable to children. A period of validity - 3 years. Not to use after the termination of a period of validity.

Issue conditions:

According to the recipe

Packaging:

10 capsules in a blister strip packaging, on 1 or 2 planimetric packagings in a pack (No. 10 × 1, No. 10 × 2).