Doxycycline

Doxycycline-Darnitsa capsules 100 mg

Instruction manual

For medical use of the drug

Structure:

Active ingredient: doxycycline;

1 capsule contains doxycycline cyclate (in terms of doxycycline) 100 mg;

excipients: lactose monohydrate, potato starch, calcium stearate.

Dosage form.

Capsules

Basic physico-chemical properties: hard capsules with a lid and a yellow body, containing yellow powder with a greenish tint with white blotches.

Pharmacotherapeutic group.

Antibacterial agents for systemic use. tetracyclines. doxycycline. code atx j01a a02.

Pharmacological properties.

Pharmacodynamics

Doxycycline is a semi-synthetic antibiotic of the broad-spectrum tetracycline group. It has a bacteriostatic effect due to the suppression of the synthesis of protein pathogens as a result of blocking the connection of aminoacyl transport RNA (tRNA) with the complex "information RNA (mRNA) - ribosome".

Doxycycline is active against gram-positive bacteria: aerobic cocci - Staphylococcus spp. (including those producing penicillinase), Streptococcus spp. (including Streptococcus pneumoniae); aerobic spore-forming bacteria - Bacillus anthracis; aerobic non-spore forming bacteria - Clostridium spp.

Also active against gram-negative bacteria: aerobic cocci - Neisseria gonorrhoeae; aerobic bacteria - Escherichia coli; Shigella spp., Salmonella spp., Enterobacter spp., Klebsiella spp., Bordetella pertussis, as well as relative to Rickettsia spp., Treponema spp., Mycoplasma spp., Chlamydia spp.

Resistant to doxycycline: Pseudomonas aeruginosa, Proteus spp., Serratia spp., Most strains of Bacteroides fragilis.

Pharmacokinetics

The drug is rapidly absorbed from the digestive tract, almost regardless of the presence of food. It binds to plasma proteins by 80–90%. The maximum plasma concentration is reached 2 hours after taking the drug. Depending on the dose, the therapeutic concentration of doxycycline in the blood persists for 18-24 hours. Quickly distributed in most body fluids, including bile, paranasal sinus secretion, pleural, synovial and ascitic fluids. The concentration in the cerebrospinal fluid changes and after parenteral administration can be 10−25% of the concentration in the blood serum. It is excreted slowly from the body. The half-life of the drug is 12-22 hours. A significant part of doxycycline is excreted unchanged with feces, approximately 40% with urine.

Clinical characteristics.

Indications.

Treatment of infections caused by sensitive strains of gram-positive and gram-negative microorganisms, as well as some other microorganisms, namely:

• respiratory tract infections: pneumonia and other diseases of the lower respiratory tract caused by sensitive strains of Streptococcus pneumoniae, Haemophilus influenza, Klebsiella pneumoniae; pneumonia caused by Mycoplasma pneumoniae; chronic bronchitis, sinusitis;
• urinary tract infections: infections caused by sensitive strains of the species Klebsiella, Enterobacter, as well as bacteria Escherichia coli, Streptococcus faecalis;
• sexually transmitted infections: infections caused by Chlamydia trachomatis, including uncomplicated urethral and endocervical infections and infections of the rectum; non-gonococcal urethritis caused by Ureaplasma urealyticum (T-mycoplasma); soft chancre, inguinal granuloma, venereal granuloma; the drug is an alternative for the treatment of gonorrhea and syphilis;
• skin infections: acne, if necessary, the use of antibiotic therapy.

Treatment of infections caused by tetracycline-sensitive microorganisms, namely:

• ophthalmic infections: infections caused by the sensitive bacteria gonococci, staphylococci and Haemophilus influenza. The infection that causes trachoma is not always eliminated, as confirmed by immunofluorescence analysis. For the treatment of paratrachoma, the drug can be used as monotherapy or in combination with other drugs;
• rickety infections: typhoid fever, Rocky Mountain spotted fever, Ku fever, tick-borne fever, endocarditis caused by Coxiella;
• other infections: ornithosis, brucellosis (when used in combination with streptomycin), cholera, bubonic plague, epidemic relapsing fever, tick-borne relapsing fever, tularemia, melioidosis; tropical chloroquine-resistant malaria and acute intestinal amebiasis (when used in combination with an amoebicide).

Prevention of the following conditions: Japanese river fever, travelers diarrhea (caused by enterotoxic Esherihia coli), leptospirosis, malaria. Prevention of malaria should be carried out according to current practice because of the possibility of developing resistance.

Alternative treatment: leptospirosis, gas gangrene, tetanus.

Contraindications

Hypersensitivity to tetracyclines or to other components of the drug; porphyria; severe liver failure; leukopenia.

Interaction with other drugs and other types of interactions.

With the combined use of the drug with other drugs, it is possible:

with antacids (aluminum, calcium, magnesium), kaolin, magnesium-containing laxatives, sodium bicarbonate, iron and zinc drugs, sucralfate, cholestyramine, cholestipol - reduced absorption of doxycycline;

with barbiturates, carbamazepine, primidone, rifampicin, phenytoin - a decrease in plasma concentration and a shortening half-life (T_1/2) doxycycline (induction of monooxygenases and acceleration of biotransformation), which can lead to a decrease in the antibacterial effect;

with antithrombotic agents, indirect anticoagulants - potentiation of the effect of the latter; it may be necessary to reduce the dose of anticoagulants;

with cyclosporine - an increase in the concentration of cyclosporine in blood plasma; this combination should be used under close supervision;

with methoxyflurane - lethal toxic effect on the kidneys;

with retinoids - increased risk of intracranial hypertension; this combination should not be used;

with methotrexate - increased toxicity of the latter; this combination should be used with caution;

with hormonal contraceptives - reduced effectiveness and increased frequency of breakthrough bleeding when taking estrogen-containing oral contraceptives;

with penicillins - a decrease in the effectiveness of the latter;

with oral vaccines against typhoid fever - a decrease in the effectiveness of the latter; this combination should not be used.

The simultaneous use of isotretinoin or other systemic retinoids and doxycycline should be avoided. The use of each of these substances was separately associated with the development of benign intracranial hypertension (pseudotumors of the brain).

Features of the application.

To reduce stomach irritation, the drug should be taken with food, washed down with a sufficient amount of water.

With prolonged use of the drug, the composition of peripheral blood should be regularly monitored, liver function tests performed, and serum urea determined.

In the treatment of infections caused by β-hemolytic group A streptococci, the duration of treatment should be at least 10 days.

In the treatment of sexually transmitted diseases with suspected concomitant syphilis, appropriate diagnostic procedures should be applied, including dark field microscopy and other tests. In such cases, monthly serological tests must be performed for at least 4 months.

Use the drug with caution in patients with impaired liver function or in individuals who receive potentially hepatotoxic drugs.Abnormal liver function associated with oral or parenteral administration of tetracyclines, including doxycycline, has been reported extremely rarely.

Use the drug with caution in patients with myasthenia gravis because drugs of the tetracycline group, including doxycycline, can cause weak neuromuscular blockade.

Kidney doxycycline excretion in patients with normal renal function is approximately 40% in 72 hours. This range may decrease to 1-5% in 72 hours in individuals with severe renal failure (creatinine clearance below 10 ml / min). Studies have not revealed a significant difference in the half-life of doxycycline from blood serum in individuals with normal and impaired renal function. Hemodialysis does not affect plasma half-life.

The antianabolic effect of tetracyclines can lead to an increase in blood urea levels. The anti-anabolic effect was not manifested when doxycycline was used in patients with impaired renal function.

Photosensitivity reactions have been reported in some individuals taking tetracyclines, including doxycycline. During treatment with doxycycline and within 4−5 days after its completion, it is recommended to protect open areas of the body from direct sunlight and artificial UV radiation. Treatment with tetracyclines, including doxycycline, should be stopped immediately at the first manifestations of erythema on the skin.

Treatment with antibacterial drugs can lead to overgrowth of insensitive microorganisms, including those of the genus Candida. To prevent the development of candidiasis simultaneously with doxycycline, it is recommended to use antifungal drugs.

Treatment with antibacterial drugs alters the normal flora of the large intestine, resulting in overgrowth of insensitive microorganisms, including Clostridium difficile. Clostridium difficile cases of diarrhea have been reported with almost all antibacterial drugs. Diarrhea can range from mild to life-threatening. Patients taking antibacterial drugs should be closely monitored due to the fact that diarrhea caused by Clostridium difficile may occur within two months after taking antibacterial drugs.

Some people taking antibacterial drugs, including doxycycline, have developed pseudomembranous colitis. The severity of this complication ranged from mild to life-threatening. It is necessary to consider this diagnosis in patients who are treated for diarrhea due to the use of antibacterial drugs.

Some individuals taking capsular or tablet forms of tetracycline class drugs, including doxycycline, have developed esophagitis and esophageal ulcers. Most of these patients took the drug immediately before bedtime or with insufficient fluid.

Mild intracranial hypertension and protrusion of the fontanel have been reported in newborns who received the drug at the maximum therapeutic dose. These complications quickly disappeared after drug withdrawal.

When examining a thyroid biopsy specimen in patients who have been taking doxycycline for a long time, staining of the tissue in micropreparations in dark brown is possible.

The use of tetracyclines can lead to an exacerbation of the systemic lupus erythematosus.

Serious skin reactions have been reported in patients who took doxycycline, such as exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic manifestations (DRESS).

If serious skin reactions occur, doxycycline should be discontinued immediately and appropriate therapy should be prescribed.

It was reported about the occurrence of photonycholysis in patients who took doxycycline.

Benign intracranial hypertension (pseudotumor of the brain) has been associated with the use of tetracyclines (including doxycycline). Benign intracranial hypertension (pseudotumor of the brain) is usually transient in nature, but when using tetracyclines (including doxycycline), cases of irreversible loss of vision due to benign intracranial hypertension (pseudotumor of the brain) have been reported. In case of visual impairment during treatment, an urgent ophthalmological examination is necessary. Since intracranial pressure may remain elevated for several weeks after discontinuation of the drug, patients should be monitored until their condition stabilizes. The simultaneous use of isotretinoin, like other systemic retinoids, with doxycycline should be avoided, since it is known that isotretinoin can also provoke benign intracranial hypertension (pseudotumor of the brain).

When conducting a fluorescence test, a false increase in the level of catecholamines in the urine may be observed.

Do not drink alcohol during treatment.

The drug contains lactose, therefore, the drug should not be used in patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Use during pregnancy or lactation.

The drug is contraindicated during pregnancy, since the use of tetracyclines during the development of teeth (during pregnancy) can cause a permanent change in the color of the teeth (yellow-brown-gray). such an adverse reaction is more common with prolonged use, but can also be observed with repeated short courses of treatment. there have also been reports of enamel hypoplasia.

The drug is contraindicated during lactation, since tetracyclines pass into breast milk.

The ability to influence the speed of reactions when driving vehicles or other mechanisms.

Until the patients individual response to the drug has been clarified, one should refrain from driving or working with other mechanisms, since treatment with doxycycline may cause visual impairment, dizziness, hypertension, tinnitus, blurred vision, scotoma, diplopia, and long-term loss of vision.

Dosage and administration.

The drug should be used orally during or after a meal (you can drink it with milk or kefir).

Adults and children over 12 years old and weighing more than 45 kg.

On the first day of treatment of acute infections, the daily dose is 200 mg once or 100 mg every 12 hours, on the following days - 100 mg. In the treatment of severe infections, it is necessary to use a drug at a dose of 200 mg per day for the entire treatment period.

The duration of the course of treatment is determined by the doctor individually, continuing treatment for at least 24–48 hours after the disappearance of the symptoms of the disease and normalization of body temperature.

Children from 12 years old and weighing less than 45 kg.

On the first day of treatment, the daily dose is 4.4 mg / kg body weight (in 1 or 2 doses), on the following days - 2.2 mg / kg body weight (in 1 or 2 doses). In the treatment of severe infections, a dose of 4.4 mg / kg of body weight may be prescribed during the entire treatment period.

Special use cases.

Acne: the drug is used at a dose of 50 mg per day for 6-12 weeks.

Sexually transmitted infections:

• uncomplicated cervical infections, urethral, ​​rectal infections caused by Chlamydia trachomatis; uncomplicated genital infections caused by Neisseria gonorrhoeae (exception - anorectal infections in men); urethritis caused by Ureaplasma urealyticum: the drug is used in a dose of 100 mg 2 times a day for 7 days;
• orchoepididymitis caused by Chlamydia trachomatis or Neisseria gonorrhoeae: the drug is used in a dose of 100 mg 2 times a day for 10 days;
• primary and secondary syphilis in patients without a confirmed pregnancy and with an allergy to penicillins (as an alternative treatment): the drug should be used at a dose of 200 mg 2 times a day for 14 days.

Epidemic relapsing fever, tick-borne relapsing fever: use the drug at a dose of 100-200 mg once, depending on the severity of the disease.

Chloroquine-resistant tropical malaria: use the drug at a dose of 200 mg per day for at least 7 days.

Prevention of malaria: the drug is used in a dose: for adults - 100 mg per day, for children from 12 years old - from 2.2 mg / kg body weight per day to a total dose of 100 mg per day. Prevention can be started 1–2 days before traveling to the region with malaria. The prophylactic use of the drug should be continued every day while in the region with malaria and for 4 weeks after the region with malaria was abandoned. The current standards for treating malaria should also be considered.

Prevention of Japanese river fever: use the drug at a dose of 200 mg once.

Prevention of travelers diarrhea in adults: use the medicine: on the first day of travel - at a dose of 200 mg once or 100 mg every 12 hours; during the next days of travel - at a dose of 100 mg. Information on the use of the drug for longer than 21 days for the purpose of prevention is not available.

Prevention of leptospirosis: the drug should be used in a dose of 200 mg once a week during the entire stay in the region with leptospirosis and 200 mg at the end of the trip. Information on the use of the drug for longer than 21 days for the purpose of prevention is not available.

Special patient groups:

• elderly patients: the drug can be used in normal doses without special warnings. Doxycycline-Darnitsa may be the drug of choice for elderly patients, since its use is less associated with the development of irritation and ulcers of the esophagus;
• patients with impaired renal function: the use of the drug in the recommended doses does not lead to the accumulation of an antibiotic (see section "Features of use");
• patients with impaired liver function: see section "Features of use".

Children.

The drug is contraindicated in children under 12 years of age.

Like other tetracyclines, doxycycline forms stable calcium complexes in any tissue that forms bones. A decrease in the level of tibia growth was observed in premature infants who received tetracycline orally at a dose of 25 mg / kg body weight every 6 hours. This adverse reaction is reversible when the drug is withdrawn.

The use of tetracyclines during the development of teeth (children under 12 years of age) can cause a permanent change in the color of the teeth (yellow-brown-gray). Such an adverse reaction is more common with prolonged use, but can also be observed with repeated short courses of treatment. There have also been reports of enamel hypoplasia.

Overdose.

Symptoms: increased manifestations of adverse reactions.

Treatment: discontinuation of the drug, gastric lavage, supportive and symptomatic therapy. Hemodialysis is ineffective.

Adverse Reactions

On the part of the hearing organs and vestibular apparatus: sensation of tinnitus.

From the gastrointestinal tract: dyspepsia, abdominal pain, dysphagia, nausea, vomiting, diarrhea. The occurrence of esophagitis and the formation of ulcers in patients who took doxycycline capsules and tablets were reported. Colitis caused by the microorganism Clostridium difficile, enterocolitis, inflammatory lesions (with monilial proliferation) in the anogenital region.

On the part of the liver and biliary tract: there have been reports of isolated cases of hepatotoxicity with a temporary increase in liver function values, impaired liver function, jaundice, hepatitis, liver failure, pancreatitis.

On the part of the kidneys and urinary system: increased levels of urea in the blood, increased levels of residual urea nitrogen.

On the part of the endocrine system: with prolonged use of tetracyclines, a brown-black coloration of the thyroid tissue micropreparation was observed. Thyroid dysfunction was not detected.

From the side of metabolism, metabolism: anorexia.

On the part of the nervous system: headache, dizziness, protrusion of a little girl’s neck, benign intracranial hypertension (pseudotumor of the brain), the symptoms of which included blurry vision, scotoma and diplopia, were reported about irreversible loss of vision.

From the cardiovascular system: arterial hypotension, tachycardia, pericarditis, hot flashes, Shenlein-Genoch disease, dyspnea.

On the part of the blood and lymphatic system: eosinophilia, hemolytic anemia, thrombocytopenia, neutropenia, porphyria.

On the part of the immune system: hypersensitivity reactions, including anaphylaxis, anaphylactoid reactions, anaphylactic shock, anaphylactoid purpura, urticaria, angioedema, exacerbation of systemic lupus erythematosus, serum sickness, shortness of breath, peripheral edema.

On the part of the skin and subcutaneous tissue: skin rashes, including maculopapulose and erythematous rashes; erythema multiforme, photosensitivity reactions of the skin, photo-nicholysis, exfoliative dermatitis, Stevens-Johnson syndrome (malignant exudative erythema), Lyells syndrome (toxic epidermal necrolysis), drug rash with symptoms of eosinophilia and systemic symptoms (DRESS syndrome).

From the musculoskeletal system and connective tissue: arthralgia, myalgia.

Infections and infestations: treatment with doxycycline can lead to the development of superinfection, such as staphylococcal enterocolitis, pseudomembranous colitis, candidiasis of the skin and mucous membranes with such manifestations: inflammation of the mucous membrane of the mouth and throat (glossitis, stomatitis), acute inflammation of the external genital organs and vagina in women (vulvovaginitis), inflammation of the anogenital region.

Others: staining and hypoplasia of tooth enamel with prolonged use of the drug.

Shelf life.

2 years.

Storage conditions.

Keep out of reach of children in the original packaging at a temperature not exceeding 25 ° C.

Packaging.

10 capsules in blister packs; 1 or 2 blisters per pack; 1000 capsules in plastic containers.

Vacation category.

On prescription.

Manufacturer.

Ciao “Darnitsa pharmaceutical company”.

The location of the manufacturer and his address of the place of business.

Ukraine, 02093, Kiev, st. Borispol, 13.