Instructions for use Doxycycline-Darnitsa capsules 100 mg No. 10
Composition
active ingredient: doxycycline;
1 capsule contains doxycycline hyclate (as doxycycline) 100 mg;
Excipients: lactose monohydrate, potato starch, calcium stearate.
Dosage form
Capsules.
Main physicochemical properties: hard capsules with a yellow cap and body, containing a yellow powder with a greenish tint with white inclusions.
Pharmacotherapeutic group
Antibacterials for systemic use. Tetracyclines. Doxycycline. ATX code J01A A02.
Pharmacological properties
Pharmacodynamics.
Doxycycline is a semi-synthetic broad-spectrum antibiotic of the tetracycline group. It exerts a bacteriostatic effect by inhibiting the protein synthesis of pathogens by blocking the binding of aminoacyl transfer RNA (tRNA) to the messenger RNA (mRNA)-ribosome complex.
Doxycycline is active against gram-positive bacteria: aerobic cocci - Staphylococcus spp. (including those that produce 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 against Rickettsia spp., Treponema spp., Mycoplasma spp., Chlamydia spp.
The following are resistant to doxycycline: Pseudomonas aeruginosa, Proteus spp., Serratia spp., and most strains of Bacteroides fragilis.
Pharmacokinetics.
The drug is rapidly absorbed from the digestive tract, practically regardless of the presence of food. It binds to plasma proteins by 80–90%. The maximum concentration in plasma is reached 2 hours after taking the drug. Depending on the dose, the therapeutic concentration of doxycycline in the blood is maintained for 18–24 hours. It is rapidly distributed into most body fluids, including bile, paranasal sinus secretion, pleural, synovial and ascitic fluids. The concentration in the cerebrospinal fluid varies and after parenteral administration can be 10–25% of the concentration in serum. It is excreted from the body slowly. The half-life of the drug is 12–22 hours. A significant part of doxycycline is excreted unchanged in feces, approximately 40% in urine.
Indication
Treatment of infections caused by susceptible strains of Gram-positive and Gram-negative microorganisms, as well as some other microorganisms, namely:
Respiratory tract infections: pneumonia and other lower respiratory tract diseases 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 Escherichia coli, Streptococcus faecalis;
sexually transmitted infections: infections caused by Chlamydia trachomatis, including uncomplicated urethral and endocervical infections and rectal infections; non-gonococcal urethritis caused by Ureaplasma urealyticum (T-mycoplasma); chancroid, granuloma inguinale, granuloma venereum; the drug is an alternative for the treatment of gonorrhea and syphilis;
Skin infections: acne, if necessary, antibiotic therapy.
Treatment of infections caused by microorganisms sensitive to tetracyclines, namely:
ophthalmic infections: infections caused by sensitive bacteria gonococci, staphylococci and Haemophilus influenza. The infection causing trachoma is not always eliminated, which is confirmed by immunofluorescence analysis. For the treatment of paratrachoma, the drug can be used as monotherapy or in combination with other drugs;
rickettsial infections: typhus group, Rocky Mountain spotted fever, Q fever, tick-borne fever, endocarditis caused by Coxiella;
other infections: ornithosis, brucellosis (when used in combination with streptomycin), cholera, bubonic plague, epidemic relapsing typhus, tick-borne relapsing fever, tularemia, melioidosis; tropical malaria resistant to chloroquine, and acute intestinal amebiasis (when used in combination with an amebicide).
Prevention of the following conditions: Japanese river fever, traveler's diarrhea (caused by enterotoxigenic Escherichia coli), leptospirosis, malaria. Malaria prophylaxis should be performed according to current practice due to the possibility of resistance development.
Alternative treatment: leptospirosis, gas gangrene, tetanus.
Contraindication
Hypersensitivity to tetracyclines or to other components of the drug; porphyria; severe hepatic insufficiency; leukopenia.
Interaction with other medicinal products and other types of interactions
When using the drug simultaneously with other drugs, it is possible:
with barbiturates, carbamazepine, primidone, rifampicin, phenytoin – decreased plasma concentration and shortened half-life (T1/2) of doxycycline (induction of monooxygenases and acceleration of biotransformation), which may 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 - increased plasma concentration of cyclosporine; 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 – a decrease in their effectiveness and an increase in the frequency of breakthrough bleeding when taking estrogen-containing oral contraceptives;
with penicillins – reduced effectiveness of the latter;
with oral typhoid vaccines – reduced effectiveness of the latter; this combination should not be used.
The concomitant use of isotretinoin or other systemic retinoids and doxycycline should be avoided. The use of either agent alone has been associated with the development of benign intracranial hypertension (pseudotumor cerebri).
Application features
To reduce stomach irritation, the medicine should be taken with meals, with sufficient water.
With prolonged use of the drug, the composition of peripheral blood should be regularly monitored, liver function tests should be performed, and the urea content in the blood serum should be determined.
When treating infections caused by group A β-hemolytic 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, including dark-field microscopy and other tests, should be used. In such cases, monthly serological tests should be performed for at least 4 months.
Use with caution in patients with impaired liver function or in individuals receiving potentially hepatotoxic drugs. Liver dysfunction 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 tetracycline drugs, including doxycycline, can cause weak neuromuscular blockade.
Renal excretion of doxycycline in patients with normal renal function is approximately 40% over 72 hours. This range may decrease to 1–5% over 72 hours in patients with severe renal impairment (creatinine clearance less than 10 mL/min). Studies have not shown a significant difference in the serum half-life of doxycycline between patients with normal and impaired renal function. Hemodialysis does not affect the serum half-life of the drug.
The anti-anabolic effect of tetracyclines may lead to an increase in blood urea levels. The anti-anabolic effect was not observed when doxycycline was used in patients with impaired renal function.
Photosensitivity reactions have been reported in some individuals taking tetracyclines, including doxycycline. It is recommended to protect exposed areas of the body from direct sunlight and artificial UV radiation during treatment with doxycycline and for 4–5 days after its termination. Treatment with tetracyclines, including doxycycline, should be discontinued immediately at the first appearance of erythema on the skin.
Treatment with antibacterial drugs may result in overgrowth of non-susceptible microorganisms, including Candida. To prevent the development of candidiasis, it is recommended to use antifungal drugs simultaneously with doxycycline.
Treatment with antibacterial drugs alters the normal flora of the large intestine, resulting in overgrowth of nonsusceptible organisms, including Clostridium difficile. Clostridium difficile-associated diarrhea has been reported with nearly all antibacterial drugs. Diarrhea may range from mild to life-threatening. Patients receiving antibacterial drugs should be closely monitored because diarrhea caused by Clostridium difficile may occur within two months of taking antibacterial drugs.
Pseudomembranous colitis has been reported in some individuals receiving antibacterial agents, including doxycycline. The severity of this complication has ranged from mild to life-threatening. This diagnosis should be considered in patients presenting with diarrhea secondary to antibacterial agents.
Mild intracranial hypertension and fontanelle protrusion have been reported in neonates receiving the drug at the maximum therapeutic dose. These complications resolved rapidly after drug withdrawal.
When examining a thyroid biopsy in patients who have been taking doxycycline for a long time, the tissue in micropreparations may turn dark brown.
The use of tetracyclines can lead to exacerbation of systemic lupus erythematosus.
Serious skin reactions such as exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms (DRESS) have been reported in patients taking doxycycline. If serious skin reactions occur, doxycycline should be discontinued immediately and appropriate therapy should be initiated.
Photoonycholysis has been reported in patients taking doxycycline.
Benign intracranial hypertension (pseudotumor cerebri) has been associated with the use of tetracyclines (including doxycycline). Benign intracranial hypertension (pseudotumor cerebri) is usually transient, but cases of irreversible vision loss due to benign intracranial hypertension (pseudotumor cerebri) have been reported with tetracyclines (including doxycycline). If visual impairment occurs during treatment, prompt 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 concomitant use of isotretinoin, as with other systemic retinoids, with doxycycline should be avoided, since isotretinoin is also known to cause benign intracranial hypertension (pseudotumor cerebri).
When performing a fluorescent test, a false increase in the level of catecholamines in the urine may be observed.
Do not drink alcoholic beverages during treatment.
The medicine contains lactose, therefore patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not take the medicine.
Use during pregnancy or breastfeeding
The drug is contraindicated during pregnancy, as the use of tetracyclines during the period of tooth development (during pregnancy) may cause permanent discoloration of the teeth (yellow-brown-gray). This adverse reaction is more common with long-term use, but can also occur with repeated short courses of treatment. Enamel hypoplasia has also been reported.
The drug is contraindicated during breastfeeding, as tetracyclines penetrate into breast milk.
Ability to influence reaction speed when driving vehicles or other mechanisms
Until the patient's individual reaction to the drug is determined, one should refrain from driving or operating other mechanisms, since visual disturbances, dizziness, arterial hypertension, tinnitus, blurred vision, scotoma, diplopia, and long-term vision loss may occur during treatment with doxycycline.
Method of administration and doses
The medicine should be taken orally during or after meals (can be washed down with milk or kefir).
Adults and children aged 12 years and over with a body weight of more than 45 kg.
On the first day of treatment of acute infections, the daily dose is 200 mg once or 100 mg at intervals of 12 hours, on the following days - 100 mg. In the treatment of severe infections, the drug should be used at a dose of 200 mg per day throughout the entire period of treatment.
The duration of the treatment course is determined by the doctor individually, continuing treatment for at least 24−48 hours after the symptoms of the disease disappear and body temperature normalizes.
Children aged 12 years and over with a body weight of up to 45 kg.
On the first day of treatment, the daily dose of the drug 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 body weight may be prescribed for the entire treatment period.
Special use cases.
Acne: the drug should be 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 should be used at a dose of 100 mg 2 times a day for 7 days;
Epididymo-orchitis caused by Chlamydia trachomatis or Neisseria gonorrhoeae: the drug should be used at a dose of 100 mg 2 times a day for 10 days;
primary and secondary syphilis in patients without 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.
Tropical malaria resistant to chloroquine: the drug should be used at a dose of 200 mg per day for at least 7 days.
Malaria prevention: the drug is prescribed in a dose: adults - 100 mg per day, children from 12 years of age - from 2.2 mg/kg body weight per day to a total dose of 100 mg per day. Prophylaxis can be started 1-2 days before traveling to a region with malaria. Prophylactic use of the drug should be continued every day during stay in a region with malaria and for 4 weeks after leaving the region with malaria. Current standards for the treatment of malaria should also be taken into account.
Prevention of Japanese river fever: the drug should be administered in a dose of 200 mg once.
Prevention of traveler's diarrhea in adults: the drug should be used: on the first day of travel - at a dose of 200 mg once or 100 mg at intervals of 12 hours; during the following days of travel - at a dose of 100 mg. There is no information on the use of the drug for longer than 21 days for the purpose of prevention.
Leptospirosis prevention: the drug should be used at a dose of 200 mg once a week during the entire stay in the region with leptospirosis and 200 mg of the drug at the end of the trip. There is no information on the use of the drug for longer than 21 days for the purpose of prevention.
Special patient groups:
Elderly patients: the drug can be used in usual doses without special precautions. Doxycycline-Darnitsa may be the drug of choice for elderly patients, as its use is less associated with the development of irritation and ulcers of the esophagus;
patients with impaired renal function: use of the drug in recommended doses does not lead to antibiotic cumulation (see section "Special instructions for use");
patients with impaired liver function: see section "Special warnings and precautions for use".
Children.
The medicine is contraindicated in children under 12 years of age.
Like other tetracyclines, doxycycline forms stable calcium complexes in any bone-forming tissue. Reduced tibia growth has been observed in premature infants given oral tetracyclines at doses of 25 mg/kg every 6 hours. This adverse reaction is reversible upon discontinuation of the drug.
Use of tetracyclines during the period of tooth development (in children under 12 years of age) may cause permanent discoloration of the teeth (yellow-brown-gray). This adverse reaction is more common with long-term use, but can also occur with repeated short courses of treatment. Enamel hypoplasia has also been reported.
Overdose
Symptoms: increased manifestations of adverse reactions.
Treatment: discontinuation of the drug, gastric lavage, supportive and symptomatic therapy. Hemodialysis is ineffective.
Side effects
From the side of the organs of hearing and vestibular apparatus: sensation of tinnitus.
Gastrointestinal: dyspepsia, abdominal pain, dysphagia, nausea, vomiting, diarrhea. Esophagitis and ulceration have been reported in patients taking doxycycline capsules and tablets. Colitis caused by Clostridium difficile, enterocolitis, inflammatory lesions (with monilial growth) in the anogenital area.
Hepatobiliary disorders: isolated cases of hepatotoxicity with transient increases in liver function tests, liver dysfunction, jaundice, hepatitis, hepatic failure, pancreatitis have been reported.
On the part of the kidneys and urinary system: increased blood urea level, increased residual urea nitrogen level.
On the part of the endocrine system: with prolonged use of tetracyclines, brown-black staining of the thyroid tissue micropreparation was observed. No thyroid dysfunction was detected.
Metabolism: anorexia.
Nervous system: headache, dizziness, fontanelle protrusion in newborns, benign intracranial hypertension (pseudotumor cerebri), symptoms of which included blurred vision, scotoma and diplopia, irreversible loss of vision has been reported.
Cardiovascular system: hypotension, tachycardia, pericarditis, hot flashes, Henoch-Schonlein disease, dyspnea.
Blood and lymphatic system disorders: eosinophilia, hemolytic anemia, thrombocytopenia, neutropenia, porphyria.
Immune system disorders: hypersensitivity reactions, including anaphylaxis, anaphylactoid reactions, anaphylactic shock, anaphylactoid purpura, urticaria, angioedema, exacerbation of systemic lupus erythematosus, serum sickness, dyspnoea, peripheral oedema.
Skin and subcutaneous tissue disorders: skin rashes, including maculopapular and erythematous rashes; erythema multiforme, skin photosensitivity reactions, photoonycholysis, exfoliative dermatitis, Stevens-Johnson syndrome (malignant exudative erythema), Lyell's syndrome (toxic epidermal necrolysis), drug rash with eosinophilia and systemic symptoms (DRESS syndrome).
Infections and infestations: treatment with doxycycline may lead to the development of superinfections, such as staphylococcal enterocolitis, pseudomembranous colitis, candidiasis of the skin and mucous membranes with the following manifestations: inflammation of the mucous membrane of the mouth and throat (glossitis, stomatitis), acute inflammation of the external genitalia and vagina in women (vulvovaginitis), inflammation of the anogenital area.
Others: discoloration and hypoplasia of tooth enamel with prolonged use of the drug.
Expiration date
2 years.
Storage conditions
Store out of the reach of children in the original packaging at a temperature not exceeding 25 °C.
Packaging
10 capsules in a contour blister pack; 1 or 2 contour blister packs in a pack; 1000 capsules in plastic containers.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Address
Ukraine, 02093, Kyiv, Boryspilska St., 13.
