Doxycycline

General characteristics. Structure:

Active agent – doxycycline (in the form of doxycycline of hyclate of 100 mg).

Excipients: lactoses monohydrate, cellulose microcrystallic, povidone (polyvinylpirrolidone), starch, calcium stearate.

Structure of a cover of the capsule: the case - gelatin, titanium dioxide (Е 171), a lid - gelatin, titanium dioxide (Е 171), blue shining (Е 133).

Pharmacological properties:

Pharmacokinetics. After oral administration, doxycycline is almost completely soaked up from an upper part of a small intestine (> 90% of the accepted dose). 1-2 hours later after reception, peak concentration of drug in plasma are reached. After reception of a single dose in 200 mg peak concentration make 3-5,3 mg/l. In the first day of treatment appoint a dose of 200 mg, and in the next days (with a 24-hour interval) single doses on 100 mg. At the expense of it equilibrium concentration of drug are quickly reached. In case of use of the scheme of 200 mg / 100 mg they are approximately at the same level, as after reception of a single dose of 200 mg. Extent of linkng of doxycycline with proteins makes 80-90%.

Doxycycline is distributed in many bodies and environments of an organism. High concentration is found in bile, and especially good fabric diffusion is reached in a liver, kidneys, lungs, a spleen, bones and generative organs. Badly gets into cerebrospinal fluid. Doxycycline passes through a placenta and it is found in maternal milk. Concentration in maternal milk makes about 30-40% of concentration in a blood plasma. The volume of distribution of doxycycline makes about 0,75 l/kg.

Doxycycline is metabolized only in insignificant degree (<10% of a dose). Allocation happens, generally in the form of microbiological active agent through kidneys (30-55%) and through intestines (by transintestinal secretion and through bile). The second way of excretion is the basic at patients with an impaired renal function. The elimination half-life makes about 16 ± 6 hours; at an abnormal liver function the elimination half-life is considerably extended. Within 24 hours in urine about 41% are found (range: 22-60%) doxycycline doses.

Pharmacodynamics. Doxycycline concerns to group of tetracyclines. Doxycycline possesses preferential bacteriostatic action. The mechanism of its action is based on suppression of ribosomalny protein synthesis, and drug works on the activators located both vnekletochno and is intracellular. The hypotoxicity is based, presumably, on much higher affinity of doxycycline to bacterial ribosomes - in comparison with ribosomes of tissues of the person.

The action spectrum of doxycycline does not differ from an action spectrum of other tetracyclines. It covers many gram-positive and gram-negative bacteria, including anaerobe bacterias and spore-formers. Doxycycline, as well as all tetracyclines, is active concerning intracellular microorganisms (a mycoplasma, a rickettsia, a chlamydia).

Action spectrum of tetracyclines.

Gram-positive activators

Gram-negative activators

Staphylococcus

Streptococci of various serological groups

Corynebacterium

Listeria monocytogenes

Clostridiums (except for C. difficile)

Propionibacterium acnes

Tropheryma whippelii

Bartonella species

Borrelia recurrentis

Brucella spp

Bacteroides (some types)

Campylobacter granulomatis Campylobacter species

Fusobacteria

Neisseria gonorrhoeae

Many Enterobacteriaceae (for example, E. coli, Citrobacter species, Klebsiella, Morganella morganii, Salmonella, Shigella, Yersinia)

Haemophilus influenzae

Pasteurella multocida

Treponema pallidum

Vibrio cholerae

Chlamydia species

Mycoplasma species

Ureaplasma urealyticum

Rickettsiae

Streptococci of groups A and B, Bacteroides fragilis, E. coli, Citrobacter species, enterococci, gonokokk, N. of influenzae, Morganella morganii, pneumococci, staphylococcus, Shigella spp. can have the secondary (acquired) resistance to doxycycline. Enterobacter aerogenes, Providencia species, Proteus spp., Serratia spp., Pseudomonas initially rezistentna to doxycycline.

Within group of tetracyclines there is a full cross resistance.

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to doxycycline, including:

- infections of upper and lower respiratory tracts (tonsillitis, pharyngitis, average otitis, sinusitis, bronchitis, pneumonia) caused by Mycoplasma pneumoniae, Chlamydia pneumoniae. Doxycycline is applied as alternative drug at patients with hypersensitivity to penicillin at the respiratory infections caused by Haemophilus influenzae, Klebsiella spp., Streptococcus pneumoniae;

- the digestive tract infections caused by strains of Escherichia coli, Entamoeba histolytica, Shigella spp., Vibrio cholerae, Clostridium spp.

- the purulent infections of skin and soft tissues caused by microorganisms, for example Clostridium spp, sensitive to drug., Propinibacterium acnes;

- infections of bodies of urinogenital system, including gonorrhea, syphilis (at hyper resistance to penicillin);

- sapropyra, brucellosis, rickettsioses, trachoma, clamidiosis.

Route of administration and doses:

Inside, washing down with a large amount of liquid (but not milk).
Adult. In the first day – 2 capsules (200 mg) a day, then – 1 capsule (100 mg) a day; at heavy infections – 2 capsules (200 mg) a day, in 1 or 2 receptions, within 5 – 10 days. Duration of a course of treatment usually makes 5-10 days, in some cases is established individually.

At gonorrhea to women appoint 2 capsules (200 mg) a day before full treatment (on average, within 5-7 days); to men appoint 2-3 capsules (200-300 mg) a day in 1 reception within 5-7 days or within 1 day on 3 capsules (300 mg) 2 times a day (the second reception in 1 h after the first).
At syphilis appoint 3 capsules (300 mg) a day, the minimum duration of treatment of 10 days. 
To patients of advanced age, and also at abnormal liver functions and kidneys (clearance of creatinine less than 60 ml/min.) it is necessary to consult previously with the doctor for individual dose adjustment of doxycycline and frequency rate of reception.

Features of use:

Patients with an impaired renal function do not have need to lower a doxycycline dose.

At prolonged use it is regularly necessary to conduct blood analyses, functions of a liver and kidneys.

During treatment by doxycycline it is necessary to avoid solar bathtubs under the open sky or in sunbeds, owing to possibility of phototoxic reactions.

It is necessary to consider that owing to reception of antibiotics of group of tetracyclines there can be inexact a determination of level of sugar, protein, urobilinigen and catecholamines in urine.

At therapy reliability of contraceptive action of hormonal contraceptives can be called by doxycycline into question. Therefore it is recommended to use non-hormonal contraceptives in addition.

In case of development of pseudomembranous colitis, depending on weight of a basic disease, it is necessary to make the decision concerning the therapy termination by doxycycline, and if necessary, to carry out the corresponding treatment (reception of specific antibiotics and chemotherapeutic means which efficiency is clinically proved) without drug withdrawal.

Doxycycline gets through a placenta. Can cause long-term discoloration of teeth, an enamel hypoplasia, suppression of growth of bones of a skeleton of a fruit, and also development of fatty infiltration of a liver.

Considering side effects of medicine, it is necessary to be careful during the driving and service of potentially dangerous mechanisms.

Side effects:

- nausea, heartburn, pressure sense in a stomach, desires to vomiting, vomiting, a meteorism, a steatorrhea, diarrhea, a pseudomembranous coloenteritis;

- pharyngitis, hoarseness, swallowing difficulty, melanoglossia;

- the increase in intracranial pressure which is shown in the form of headaches, nausea, vomiting and a vision disorder owing to a papilledema;

- phototoxic reactions – at solar radiation of skin: reddening, hypostasis, formation of bubbles, discoloration of skin and, extremely seldom, changes from nails – separation of a nail from a nail bed and discoloration of a nail plate;

- leukopenia, leukocytosis, thrombocytopenia, anemia, lymphocytopenia, lymphadenopathy, atypical lymphocytes and toxic granularity of granulocytes;

- damage of a liver, pancreatitis;

- nephrotoxic defeats, an aggravation of already available disturbances of functions of kidneys, intersticial nephrite, an acute renal failure, an anury;

- a generalized dieback, an erythema, a small tortoiseshell, a skin itch, a mnogoformny exudative erythema, reversible local cutaneous dropsies, mucous membranes or joints (Quincke's disease), asthma, an acute anaphylaxis, persistent medicinal rash on generative organs and other body parts;

- reaction, similar to a serum disease, accompanied with fever, headaches and joint pains;

- heavy acute symptoms of hypersensitivity, such, as, a face edema, swelling of language, internal hypostasis of a throat with narrowing of respiratory tracts, tachycardia, suffocation (asthma), falling of arterial pressure up to shock and a cardiac standstill;

- exfoliative dermatitis, Lyell's disease;

- the candidiasis of skin and mucous membranes (especially, generative organs and mucous membranes of a mouth and intestines) accompanied with such symptoms as an inflammation of a mucous membrane of a mouth and throat (stomatitis, a glossitis), acute inflammations of external genitals and a vagina at women (vulvovaginitis), and also an itch in proctal area;

- disturbances of a blood coagulation and hamaturia;

- paresthesias, mialgiya, arthralgias;

- tachycardia;

- concern and condition of fear;

- epileptic seizures;

- disturbance or loss of olfactory and flavoring feeling.

Interaction with other medicines:

Absorption of doxycycline from digestive tract decreases under the influence of 2-or 3-valent cations of aluminum, calcium (milk, dairy products and kaltsiysoderzhashchy fruit juice) and the magnesium which are a part of antiacid means and also under the influence of iron preparations, absorbent carbon and a holestiramin. Therefore the medicines or food stuffs containing these cations should be accepted at an interval of 2-3 hours concerning doxycycline reception time.

Rifampicin, barbiturates, anticonvulsants (carbamazepine, diphenylhydantoin and Primidonum), and also chronic alcohol abuse, owing to induction of enzymes in a liver, accelerate doxycycline metabolism. As a result effective concentration of doxycycline in blood at reception of usual doses of drug cannot be reached therapeutic.

Doxycycline strengthens effect of sulphonylurea (oral anti-diabetic means) and anticoagulants like дикумарол. At the combined use it is necessary to exercise control of indicators of level of sugar in blood and parameters of a blood coagulation and, if necessary, to reduce a dose of the above-stated medicines.

At simultaneous use of doxycycline and cyclosporine A toxic action of an immunosuppressant increases.

Therapy by doxycycline in a combination with a metoksifluranovy anesthesia can lead to a renal failure.

Before an initiation of treatment, during it and, directly after therapy izotretinoiny acne rash, it is necessary to refrain from therapy by doxycycline as both medicines can cause increase in intracranial pressure.

It is necessary to avoid a concomitant use of doxycycline and beta лактамных antibiotics as it leads to decrease in antibacterial efficiency.

At simultaneous use of theophylline and tetracyclines the probability of emergence of side effects from digestive tract increases.

Contraindications:

- hypersensitivity to active or to excipients, tetracyclines;

- heavy abnormal liver functions;

- hereditary lactose intolerance, fructose, galactoses, lactose intolerance;

- children's and teenage age up to 18 years;

- pregnancy and period of a lactation.

Overdose:

Now about cases of overdose it was not reported.

Symptoms: however at overdose there is a danger of parenchymatous damages of a liver and kidneys, and also pancreatitis.

Treatment: at peroral overdose of doxycycline yet not absorbed substance has to be connected in not soaked up chelate complexes by reception of antiacid drugs or salts of calcium and magnesium. Treatment by drug has to be immediately stopped. The symptomatic treatment is carried out. The hemodialysis or peritoneal dialysis are ineffective.

Storage conditions:

To store in the dry, protected from light place at a temperature not above 30 °C. To store in the place, unavailable to children! 

Issue conditions:

According to the recipe

Packaging:

On 10 capsules in a blister strip packaging from a film of polyvinyl chloride and aluminum foil. Planimetric packagings place in boxes from a cardboard. Put the approved instructions on a medical use in each box in the state and Russian languages.