Instructions for use Doxycycline-Teva tablets 100 mg No. 10
Composition
active ingredient: doxycycline monohydrate;
1 tablet contains 100 mg of doxycycline as doxycycline monohydrate;
Excipients: microcrystalline cellulose, sodium starch glycolate (type A), talc, magnesium stearate, colloidal anhydrous silicon dioxide, purified water.
Dosage form
Pills.
Main physicochemical properties: greenish-yellow with uniform or non-uniform color, "speckled", round biconvex tablets with a break line on one side.
Pharmacotherapeutic group
Antibacterial agent for systemic use. ATX code J01A A02.
Pharmacological properties
Pharmacodynamics
Doxycycline has a bacteriostatic effect; its antimicrobial effect is realized by inhibiting protein synthesis. The drug is effective against a wide range of gram-positive and gram-negative bacteria and some other microorganisms.
Pharmacokinetics
Absorption. After oral administration, doxycycline is almost completely absorbed in the upper small intestine (>90% of the dose). Significant concentrations are reached within 30 minutes, and maximum plasma concentrations are reached within 1-2 hours. After a single dose of 200 mg, the maximum concentration was 3-5.3 mg/l. When used under therapeutic conditions (200 mg on the 1st day of treatment and 100 mg on subsequent days), the steady-state concentration is reached quickly and is almost as high as after a single dose of 200 mg.
The plasma elimination half-life in healthy subjects is approximately 16±6 hours; it may be slightly prolonged in patients with renal impairment and significantly prolonged in patients with liver disease. Protein binding of doxycycline is 80-90%.
Distribution. The drug is rapidly distributed throughout the body, with relatively little penetration into the central nervous system, even through inflamed meninges. High concentrations in the gallbladder and good tissue penetration are achieved in the liver, kidneys, lungs, spleen, bones, and genitals. The apparent volume of distribution of doxycycline is approximately 0.75 l/kg.
Biotransformation: Doxycycline is metabolized in humans only to a minor extent (≤10% of the dose).
Excretion: Excretion occurs mainly in the form of microbiologically active substance through the intestine (by transintestinal secretion or via the gallbladder), with 30-55% excreted by the kidneys. Approximately 41% (range: 22-60%) of the doxycycline dose is recovered in the urine within 24 hours. Due to these pharmacokinetic features, the half-life of doxycycline is slightly prolonged in patients with significant renal impairment.
Indication
For the treatment of infections caused by susceptible strains of Gram-positive and Gram-negative microorganisms and some other microorganisms, namely:
Respiratory tract infections: pneumonia and other lower respiratory tract diseases caused by sensitive strains of Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, etc. 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, etc.
Sexually transmitted diseases: 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. Doxycycline is an alternative drug for the treatment of gonorrhea and syphilis.
Skin infections: acne, if necessary, antibiotic therapy.
Since doxycycline belongs to the group of tetracycline antibiotics, it can be used for infections caused by microorganisms sensitive to tetracyclines, namely:
Ophthalmic infections: infections caused by susceptible gonococci, staphylococci and Haemophilus influenzae. The infection causing trachoma is not always eliminated, as confirmed by immunofluorescence analysis. For the treatment of paratrachoma, doxycycline can be used as monotherapy or in combination with other drugs.
Rickettsial infections: Rocky Mountain spotted fever, typhus group, Q fever, Coxiella endocarditis, tick-borne fever.
Other infections: ornithosis, brucellosis (when used in combination with streptomycin), cholera, bubonic plague, epidemic relapsing typhus; tick-borne relapsing fever; tularemia, melioidosis, chloroquine-resistant tropical malaria, and acute intestinal amebiasis (when used in combination with an amebicide).
Doxycycline is an alternative drug for the treatment of leptospirosis, gas gangrene, and tetanus.
Doxycycline is indicated for the prophylaxis of the following conditions: Japanese river fever, traveler's diarrhea (caused by enterotoxigenic Escherichia coli), leptospirosis, malaria. Malaria prophylaxis should be administered in accordance with current practice due to the possibility of resistance development.
Contraindication
Hypersensitivity to doxycycline or other tetracyclines or to any of the excipients of the medicinal product; severe liver dysfunction; pregnancy or breastfeeding (see also section "Use during pregnancy or breastfeeding"); children under 12 years of age (see also section "Children").
Interaction with other medicinal products and other types of interactions
The effect of other drugs on the action of doxycycline
Absorption of doxycycline from the digestive tract may be reduced by concomitant use of antacids containing aluminum, calcium, magnesium, or by concomitant use of other drugs and products containing these cations (e.g., milk, dairy products, and fruit juices containing calcium), or by oral administration of zinc, iron or bismuth salts, activated charcoal, colestipol, or cholestyramine. The use of doxycycline with such drugs should be spaced out as much as possible.
Rifampicin, barbiturate-class inducing agents, anticonvulsants such as carbamazepine, diphenylhydantoin (phenytoin) and primidone, and chronic alcohol use may accelerate the hepatic breakdown of doxycycline by inducing liver enzymes, making it impossible to achieve therapeutically effective blood concentrations of doxycycline at standard doses. In such cases, an increase in the daily dose of doxycycline should be considered.
The effect of doxycycline on the action of other drugs
Doxycycline may enhance the hypoglycemic effect of sulfonylureas (oral antidiabetic agents). When used in combination, blood glucose levels should be monitored and, if necessary, the doses of these drugs should be reduced.
There have been reports of prolongation of prothrombin time in patients taking anticoagulants (e.g. warfarin, phenprocoumon) and doxycycline. Tetracyclines reduce plasma prothrombin activity, so a reduction in the dose of anticoagulants may be necessary.
Doxycycline may increase plasma concentrations of cyclosporine A, increasing the toxic effect of the immunosuppressant. Concomitant use of these drugs should be accompanied by careful monitoring.
Concomitant use with methotrexate may lead to increased toxicity of the latter.
Other types of interactions
Concomitant use of methoxyflurane or other potentially nephrotoxic agents and doxycycline may cause potentially fatal nephrotoxic adverse reactions.
Doxycycline should be avoided for some time before, during and after treatment of acne with isotretinoin (or other retinoids), as both drugs can in some cases lead to reversible increased intracranial pressure (Pseudotumor cerebri) (see section "Adverse reactions").
With simultaneous treatment with digoxin or digoxin derivatives, there is a risk of increasing the concentration of digoxin in the blood plasma, which may lead to digoxin intoxication (nausea, vomiting, dizziness, fatigue, cardiac arrhythmias).
Bacteriostatic drugs can negatively affect drugs with bactericidal action, therefore, the simultaneous use of doxycycline and beta-lactam antibiotics should be avoided, as this may lead to a decrease in antibacterial activity.
The simultaneous use of theophylline and doxycycline increases the risk of gastrointestinal side effects.
Several cases of pregnancy and breakthrough bleeding have been reported with the concomitant use of tetracycline antibiotics and oral contraceptives.
Tetracycline can inhibit the breakdown of ergot alkaloids in the liver (individual cases of ergotism are possible).
Incorrect laboratory test results
Urine glucose tests may be falsely positive when using the copper sulfate (Benedict) method. Urine sugar tests may be falsely negative when using glucose oxidase reagents. Falsely elevated urinary catecholamine levels may be observed when using fluorometric tests.
Taking tetracyclines may lead to inaccurate results of laboratory tests to determine the level of protein and urobilinogen in the urine.
Application features
Patients with impaired hepatic function. Doxycycline should be used with caution in patients with impaired hepatic function and in those receiving concomitant potentially hepatotoxic drugs. Liver function tests have been reported rarely with both oral and parenteral administration of tetracyclines, including doxycycline. With prolonged use (i.e., longer than 21 days), regular blood tests, liver function tests, and kidney function tests should be performed. With prolonged treatment, consideration should be given to the possibility of vitamin B deficiency.
Patients with renal impairment. In patients with normal renal function, the renal excretion of doxycycline is approximately 40% per 72 hours. This figure may decrease to 1-5% per 72 hours in patients with severe renal insufficiency (creatinine clearance below 10 ml/min). Studies have shown that there is no significant difference in the serum half-life of doxycycline in patients with normal renal function and in patients with renal insufficiency. Hemodialysis does not affect the serum half-life of doxycycline.
The anti-anabolic effects of tetracyclines may increase blood urea levels. Studies have not shown that such an anti-anabolic effect can occur when doxycycline is used in patients with renal insufficiency.
Tetracyclines can cause nephrotoxic lesions or aggravate existing renal damage (characterized by increased serum creatinine and urea levels).
Serious skin reactions: 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 receiving doxycycline (see Adverse Reactions). If serious skin reactions occur, doxycycline should be discontinued immediately and appropriate therapy should be initiated.
Overgrowth of microflora. Treatment with doxycycline may result in selection of microbial overgrowth on the skin or mucous membranes, particularly the genital tract and the oral or intestinal mucosa, of non-susceptible pathogens (e.g. Candida) (see section "Adverse reactions"). Emerging infections require treatment.
Pseudomembranous colitis has been reported in patients receiving antibacterial agents, including doxycycline. The severity of the disease has ranged from mild to life-threatening. It is important to consider this diagnosis in patients with diarrhea secondary to antibacterial therapy.
Clostridium difficile-associated diarrhea (CDAD) has been reported with the use of antibacterial agents, including doxycycline, and has ranged in severity from mild to fatal colitis. Antibacterial agents disrupt the normal intestinal flora and lead to overgrowth of C. difficile. C. difficile produces toxins A and B, which in turn contribute to the development of CDAD.
Toxin-producing strains of C. difficile can increase morbidity and mortality because such infections are resistant to antibacterial therapy and may require colectomy. It is important to consider this diagnosis in patients with diarrhea secondary to antibacterial therapy. If confirmed, doxycycline should be discontinued immediately and appropriate treatment should be initiated immediately. Inhibitors of intestinal motility are contraindicated. A careful history is necessary because CDAD has been reported to develop even after more than 2 months of antibacterial therapy.
Esophagitis: Esophagitis and esophageal ulcers have been reported with tetracyclines, including doxycycline, in tablet and capsule form. Most patients with these complaints took the drug immediately before bedtime or with insufficient fluid intake.
Porphyria: Rare reports of porphyria have been reported in patients receiving tetracyclines.
Venereal diseases. During treatment of venereal diseases, if concomitant syphilis is suspected, appropriate diagnostics should be performed, including dark-field microscopy. In such cases, serological tests should be performed monthly for at least 4 months.
Some patients with spirochetal infections may develop a Jarisch-Herxheimer reaction shortly after starting treatment with doxycycline. In such cases, patients should be explained that this reaction is a consequence of antibacterial therapy for spirochetal infections and is usually self-limiting.
Infections caused by β-hemolytic streptococci. For infections caused by group A β-hemolytic streptococci, treatment should be continued for at least 10 days.
Myasthenia gravis: Due to the possibility of mild neuromuscular blockade, the drug should be used with caution in patients with myasthenia gravis.
Systemic lupus erythematosus. The use of tetracyclines may lead to exacerbation of systemic lupus erythematosus.
Benign intracranial hypertension. Fontanelle protrusion has been reported in infants treated with tetracyclines. 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 well as other systemic retinoids, with doxycycline should be avoided, as isotretinoin is also known to cause benign intracranial hypertension (pseudotumor cerebri). (see section “Interaction with other medicinal products and other forms of interaction”).
Children. Use of tetracyclines during the period of tooth development (second half of pregnancy, infants and children under 8 years of age) may lead to irreversible discoloration of the teeth (yellow-gray-brown). This adverse reaction occurs more frequently with long-term treatment, but has also been observed after repeated short courses of treatment. Hypoplasia of tooth enamel has also been reported.
Ability to influence reaction speed when driving vehicles or other mechanisms
The effect of doxycycline on the ability to drive or use machines has not been studied. If adverse reactions such as hypotension, tinnitus, blurred vision, scotoma, diplopia, or prolonged vision loss occur, you should refrain from driving or operating machinery.
Use during pregnancy or breastfeeding
Pregnancy
The drug is contraindicated for use during pregnancy. The risks associated with the use of tetracyclines during pregnancy are mainly due to their effect on the development of teeth, bones and skeleton (see section "Special instructions" for use during the period of tooth development).
During pregnancy, there is an increased risk of liver damage when taking tetracyclines.
Breast-feeding
Tetracyclines penetrate into breast milk, therefore the use of the drug is contraindicated during breastfeeding (see the section "Special instructions" regarding use during the period of tooth development).
Method of administration and doses
The drug should be taken regularly in the morning during breakfast or another meal, with plenty of liquid (not milk or dairy products), while in an upright position. It is not recommended to go to bed immediately after taking the drug. Taking it after or during a meal helps to reduce the frequency of gastrointestinal disorders and only slightly affects the rate of absorption.
Adults. The usual dose of doxycycline for the treatment of acute infections in adults is 200 mg on the first day of treatment (as a single dose or 100 mg every 12 hours) and 100 mg daily on subsequent days. In the treatment of severe infections, the drug should be used at a dose of 200 mg daily for the entire period of treatment.
Exceeding the recommended dose may lead to an increase in the frequency of adverse reactions. Therapy should be continued for 24-48 hours after the disappearance of symptoms of the disease and fever.
In case of streptococcal infections, the use of the drug should be continued for 10 days to prevent the development of rheumatic fever or glomerulonephritis.
Children. For children aged 12 years and over with a body weight of up to 45 kg, the recommended dose is 4.4 mg/kg body weight (on the first day of treatment, the recommended dose should be administered in 1 or 2 doses), on the following days the dose is 2.2 mg/kg body weight (in 1 or 2 doses); in more severe infectious diseases, up to 4.4 mg/kg body weight can be prescribed.
Children weighing more than 45 kg should be given the usual adult dose.
Treatment of certain infections
Acne: The recommended dose is 50 mg per day with food (including liquid) for 6-12 weeks.
Sexually transmitted diseases: for the treatment of diseases such as uncomplicated gonococcal infections (exception - anorectal infections in men), uncomplicated urethral and endocervical infections and rectal infections caused by Chlamydia trachomatis, non-gonococcal urethritis caused by Ureaplasma urealyticum, the recommended dose is 100 mg 2 times a day for 7 days.
For the treatment of acute epididymo-orchitis caused by Chlamydia trachomatis or Neisseria gonorrhoeae, the drug should be administered at 100 mg 2 times a day for 10 days.
For the treatment of primary and secondary syphilis, the recommended dose of the drug for patients without confirmed pregnancy and with an allergy to penicillins is 200 mg orally 2 times a day for 2 weeks (as an alternative to penicillin therapy).
Chloroquine-resistant tropical malaria: the recommended dose is 200 mg per day for at least 7 days due to the potential for severe infectious disease.
A fast-acting schizontocide (e.g. quinine) should always be used as an adjunct to doxycycline, the dose of which varies depending on the case, due to the potential severe course of the infectious disease.
Malaria prevention: The recommended dose for adults is 100 mg per day. For children aged 12 years and over, the recommended dose is 2 mg/kg per day up to a total dose of 100 mg per day. Prophylaxis can be started 1-2 days before travel to an area with malaria. Prophylaxis should be continued daily during travel to an area with malaria and for 4 weeks after leaving an area with malaria. Current standards for the treatment of malaria should also be taken into account.
Prevention of Japanese river fever: the recommended dose of the drug is 200 mg once.
Prevention of traveler's diarrhea in adults: The recommended dose is 200 mg on the first day of travel (administered as a single dose of 200 mg or 100 mg every 12 hours) and 100 mg daily for the following days of travel. There is no information on the use of the drug for longer than 21 days for the purpose of prevention.
Leptospirosis prevention: The recommended dose is 200 mg once a week during the entire stay in the leptospirosis-prone area and 200 mg 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.
Use in elderly patients: the drug can be used in normal doses without special precautions. There is no need for dose adjustment in cases of impaired renal function.
Use in patients with impaired renal function: use of the drug in recommended doses does not lead to antibiotic accumulation in this category of patients (see section "Special instructions for use").
Use in patients with impaired liver function: see section "Special warnings and precautions for use".
Children
The drug is contraindicated for use in children under 12 years of age.
Like other tetracyclines, Doxycycline-Teva forms stable calcium complexes in any bone-forming tissue. Growth retardation of the tibia has been observed in premature infants receiving tetracyclines orally at a dose of 25 mg/kg every 6 hours. This adverse reaction is reversible upon discontinuation of the drug.
Overdose
Doxycycline is not acutely toxic after a single oral administration of several therapeutic doses. Acute intoxications caused by doxycycline have not yet been described in the literature. Overdose may manifest as damage to the liver parenchyma, kidneys, and the development of pancreatitis.
In case of overdose, the drug should be discontinued immediately, gastric lavage and symptomatic therapy should be performed. In case of overdose of doxycycline taken orally, it is possible to use antacids, magnesium or calcium salts to bind the unabsorbed part of the drug, since tetracycline can form chelate complexes with these substances that are not subject to absorption. Dialysis has almost no effect on the half-life of the drug from the blood serum, so it is ineffective in overdose.
Adverse reactions
The following adverse reactions have been reported in patients receiving tetracyclines, including doxycycline. The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).
Infections and infestations
Rare: Candida colonization of the skin or mucous membranes (namely the genital tract and the mucous membrane of the oral cavity or intestines) with symptoms such as inflammation of the mucous membrane of the oral cavity and nasopharynx (glossitis, stomatitis), acute inflammation of the external genitalia and vagina in women (vulvovaginitis), proctitis, itching in the anal area (anal pruritus).
From the side of the hematopoietic and lymphatic system
Uncommon: blood coagulation disorders.
Rare: leukocytosis, thrombocytopenia, hemolytic anemia, neutropenia, eosinophilia, lymphocytopenia, lymphadenopathy, presence of atypical lymphocytes and toxic granulocyte granularity.
On the part of the immune system
Common: anaphylactic reactions (including hypersensitivity, Henoch-Schonlein purpura, hypotension, pericarditis, angioedema, exacerbation of systemic lupus erythematosus, asthma, dyspnoea, serum sickness, peripheral oedema, tachycardia, urticaria).
Rare: anaphylactic shock, drug rash with eosinophilia and systemic symptoms (DRESS).
Frequency not known: Jarisch-Herxheimer reaction (see section "Special warnings and precautions for use").
Metabolism and nutrition
Rare: anorexia, porphyria.
From the psyche and nervous system
Rare: agitation, anxiety; paraesthesia; benign intracranial hypertension (Pseudotumor cerebri), possible symptoms of which are headache, nausea, vomiting, visual disturbances (blurred vision, scotoma, diplopia) or loss of vision due to optic disc edema (cases of irreversible vision loss have been reported); fontanelle protrusion; impaired or lost sense of smell and taste, in some cases partially irreversible.
Very rare: convulsions.
From the organs of vision
Very rare: transient myopia.
From the side of the organs of hearing and labyrinth
Rare: ringing in the ears.
From the vascular side
Rare: hot flashes.
Gastrointestinal tract
Common: nausea, vomiting, flatulence, steatorrhea.
Uncommon: dyspepsia (heartburn/gastritis), inflammation of the oral and nasopharyngeal mucosa, dysphonia, black "hairy" tongue, irreversible tooth discoloration with enamel damage when used during teething.
Rare: pancreatitis, pseudomembranous colitis (diarrhea due to C. difficile), esophageal ulcers, esophagitis, enterocolitis, abdominal pain, diarrhea, dysphagia, glossitis. Common symptoms of esophagitis and esophageal ulcers include odynophagia, chest pain, and dysphagia.
Frequency unknown: tooth discoloration (reversible discoloration of the surface of permanent teeth has been reported with doxycycline).
Hepatobiliary system
Rare: hepatic failure, hepatitis, liver function abnormalities, jaundice, hepatotoxicity with transient elevations in liver function tests.
Skin and subcutaneous tissue disorders
Very common: photosensitivity reactions with erythema, skin oedema and blistering.
Common: Rashes, including maculopapular and erythematous rashes.
Rare: severe skin symptoms with systemic reactions that may be life-threatening (e.g. erythema multiforme, exfoliative dermatitis,
Stevens-Johnson syndrome, toxic epidermal necrolysis), peeling and discoloration of the nails.
Musculoskeletal and connective tissue disorders
Uncommon: reversible bone growth retardation when used during pregnancy and in children under 8 years of age.
Rare: myalgia, arthralgia.
Renal and urinary disorders
Uncommon: hematuria.
Rare: increased blood urea nitrogen.
Very rare: renal damage such as interstitial nephritis, acute renal failure, anuria.
Other violations
Frequency unknown: microscopic brown-black discoloration of thyroid tissue has been observed after prolonged treatment (without impairment of thyroid function).
Expiration date
5 years.
Storage conditions
Store at a temperature not exceeding 30 ºС in a place inaccessible to children.
Packaging
10 tablets in a blister; 1 blister in a box.
Vacation category
According to the recipe.
Producer
Merkle GmbH, Germany.
Location of the manufacturer and its business address
Ludwig-Merkle-Strasse 3, 89143 Blaubeuren, Germany.
