Xedocine^® (Tablets) Instructions for Use

Marketing Authorization Holder

Stada Arzneimittel, AG (Germany)

Manufactured By

Rottendorf Pharma, GmbH (Germany)

ATC Code

J01AA02 (Doxycycline)

Active Substance

Doxycycline (Rec.INN registered by WHO)

Dosage Forms

	Xedocine®	Tablets 100 mg: 10 or 20 pcs.
		Tablets 200 mg: 10 or 20 pcs.

Dosage Form, Packaging, and Composition

Tablets light brown with a grayish tint with inclusions, round, biconvex, marked “A6”.

Excipients: microcrystalline cellulose, sodium carboxymethyl starch (sodium starch glycolate (type A)), magnesium stearate.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.

Tablets light brown with a grayish tint with inclusions, round, biconvex, marked “A7”.

Excipients: microcrystalline cellulose, sodium carboxymethyl starch (sodium starch glycolate (type A)), magnesium stearate.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

Antibiotic of the tetracycline group

Pharmacotherapeutic Group

Antibiotic-tetracycline

Pharmacological Action

A semisynthetic tetracycline, a broad-spectrum bacteriostatic antibiotic. Penetrating into the cell, it acts on intracellularly located pathogens. It suppresses protein synthesis in the microbial cell, disrupts the binding of transport aminoacyl-tRNA with the 30S subunit of the ribosomal membrane.

Highly sensitive are: gram-positive microorganisms Staphylococcus spp. (including Staphylococcus aureus, Staphylococcus epidermidis), Streptococcus spp. (including Streptococcus pneumoniae), Clostridium spp., Listeria spp.; and gram-negative microorganisms: Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae, Klebsiella spp., Entamoeba histolytica, Escherichia coli, Shigella spp., Enterobacter spp., Salmonella spp., Yersinia spp. (formerly Pasteurella spp.), Bacteroides spp.. The most sensitive are Haemophilus influenzae (91-96%) and intracellular pathogens. The drug is also active against Rickettsia spp., Treponema spp., Mycoplasma spp., Chlamydia spp.

Pseudomonas aeruginosa, Proteus spp., Serratia spp., most strains of Bacteroides fragilis are resistant to the drug.

Pharmacokinetics

Absorption is rapid and high (about 100%). Food intake does not significantly affect the degree of absorption. It has a high degree of solubility in lipids and low affinity for binding with calcium ions.

After oral administration of 200 mg, the time to reach C_max is 2.5 hours, the value of C_max is 2.5 µg/ml, after 24 hours after administration – 1.25 µg/ml. Binding to plasma proteins is 80-93%.

It penetrates well into organs and tissues; 30-45 minutes after oral administration, it is detected in therapeutic concentrations in the liver, kidneys, lungs, spleen, bones, teeth, prostate gland, eye tissues, in pleural and ascitic fluids, bile, synovial exudate, exudate of the maxillary and frontal sinuses, in the fluid of the gingival sulci. It penetrates poorly into the cerebrospinal fluid (10-20% of the plasma level). It penetrates the placental barrier and is detected in breast milk. The volume of distribution is 0.7 l/kg.

It is metabolized in the liver by 30-60%. The half-life is 10-16 hours (mainly 12-14 hours, on average – 16.3 hours). With repeated administration, the drug may accumulate. It accumulates in the reticuloendothelial system and bone tissue. In bones and teeth, it forms insoluble complexes with calcium ions.

It is excreted with bile, where it is found in high concentration. It undergoes enterohepatic recirculation, excreted through the intestine (20-60%); 40% of the taken dose is excreted by the kidneys within 72 hours (of which 20-50% – unchanged), in severe chronic renal failure – only 1-5%. In patients with impaired renal function or azotemia, gastrointestinal secretion is an important route of excretion.

Indications

Infectious and inflammatory diseases caused by susceptible microorganisms

• Respiratory tract infections (pharyngitis, acute and chronic bronchitis, tracheitis, bronchopneumonia, lobar pneumonia, lung abscess, pleural empyema);
• ENT infections (otitis, tonsillitis, sinusitis, etc.);
• Infections of the genitourinary system (cystitis, pyelonephritis, prostatitis, urethritis, urethrocystitis, urogenital mycoplasmosis, endometritis, endocervicitis, acute orchiepididymitis, gonorrhea, chlamydia of various localization, syphilis);
• Infections of the biliary tract and gastrointestinal tract (cholecystitis, cholangitis, gastroenterocolitis, bacterial dysentery, “traveler’s diarrhea”);
• Skin and soft tissue infections (phlegmon, abscesses, furunculosis, felons, infected burns, wounds, etc.);
• Infectious eye diseases caused by Chlamydia spp. as part of complex therapy, yaws, yersiniosis, legionellosis, rickettsiosis, Q fever, Rocky Mountain spotted fever, typhus (including epidemic, tick-borne relapsing), Lyme disease stage I, bacillary and amoebic dysentery, tularemia, cholera, actinomycosis, malaria; as part of combination therapy – leptospirosis, trachoma, psittacosis, ornithosis, granulocytic ehrlichiosis; whooping cough, brucellosis, osteomyelitis.

Prevention of postoperative purulent complications; malaria caused by Plasmodium falciparum, during short-term travels (less than 4 months) in areas where strains resistant to chloroquine and/or pyrimethamine-sulfadoxine are common.

ICD codes

Dosage Regimen

Orally, in adults and children over 8 years of age weighing more than 45 kg, the average daily dose is 0.2 g on the first day (divided into 2 doses – 0.1 g 2 times a day), then 0.1 g/day (in 1-2 doses). For chronic infections (especially of the urinary system) – 200 mg/day throughout the entire therapy period.

For the treatment of gonorrhea, one of the following regimens is prescribed: acute uncomplicated urethritis – a course dose of 0.5 g (1 dose – 0.3 g, subsequent 2 – 0.1 g each with an interval of 6 hours) or 0.1 g/day until complete cure (in women) or 0.1 g 2 times a day for 7 days (in men); for complicated forms of gonorrhea, the course dose is 0.8-0.9 g, which is distributed over 6-7 doses (0.3 g – 1 dose, then with an interval of 6 hours for 5-6 subsequent ones).

For the treatment of syphilis – 0.3 g/day for at least 10 days.

For uncomplicated infections of the urethra, cervix and rectum caused by Chlamydia trachomatis, 0.1 g 2 times a day is prescribed for at least 7 days.

Infections of the male genital organs – 0.1 g 2 times a day for up to 4 weeks.

Treatment of malaria resistant to chloroquine – 0.2 g/day for 7 days (in combination with schizontocidal drugs – quinine); malaria prophylaxis – 0.1 g once a day 1-2 days before the trip, then daily during the trip and for 4 weeks after return; for children over 8 years old – 2 mg/kg once a day.

Traveler’s diarrhea (prophylaxis) – 0.2 g on the first day of the trip (in one dose or 0.1 g 2 times a day), then 0.1 g once a day for the entire period of stay in the region (no more than 3 weeks).

Treatment of leptospirosis – 0.1 g orally 2 times a day for 7 days; leptospirosis prophylaxis – 0.2 g once a week during the period of stay in the disadvantaged area and 0.2 g at the end of the trip.

Prevention of infections after medical abortion – 0.1 g 1 hour before abortion and 0.2 g – 30 minutes after.

For acne – 0.1 g/day, course – 6-12 weeks.

Maximum daily doses for adults – up to 0.3 g/day or up to 0.6 g/day for 5 days in severe gonococcal infections.

In children 8-12 years old weighing up to 45 kg, the average daily dose is 4 mg/kg on the first day, then – 2 mg/kg per day (in 1-2 doses). In severe infections, 4 mg/kg is prescribed every 12 hours.

In the presence of severe hepatic insufficiency, a reduction in the daily dose of doxycycline is required, since it gradually accumulates in the body (risk of hepatotoxic effect).

Adverse Reactions

From the nervous system: benign increase in intracranial pressure (decreased appetite, vomiting, headache, optic disc edema), toxic effect on the central nervous system (dizziness).

From the digestive system: nausea, constipation or diarrhea, glossitis, dysphagia, esophagitis (including erosive), gastritis, ulceration of the stomach and duodenum, enterocolitis (due to the proliferation of resistant strains of staphylococci).

Allergic reactions: maculopapular rash, skin itching, skin hyperemia, angioneurotic edema, anaphylactoid reactions, drug-induced lupus erythematosus.

From the hematopoietic organs: hemolytic anemia, thrombocytopenia, neutropenia, eosinophilia.

Other: photosensitivity; superinfection; persistent discoloration of tooth enamel; inflammation in the anogenital perineal area; candidiasis (vaginitis, glossitis, stomatitis, proctitis); dysbacteriosis.

Contraindications

• Hypersensitivity;
• Porphyria;
• Severe hepatic insufficiency;
• Leukopenia;
• Children under 8 years of age – possibility of formation of insoluble calcium ion complexes with deposition in the bone skeleton, enamel and dentin of teeth;
• Pregnancy and lactation period.

Use in Pregnancy and Lactation

It is prohibited to take this drug during pregnancy and lactation.

Use in Hepatic Impairment

Contraindicated in severe hepatic insufficiency.

In the presence of hepatic insufficiency, a reduction in the daily dose of doxycycline is required, as it gradually accumulates in the body (risk of hepatotoxic effect).

Pediatric Use

Contraindicated in children under 8 years of age (possibility of formation of insoluble calcium ion complexes with deposition in the bone skeleton, enamel and dentin of teeth).

Special Precautions

To prevent local irritant effects (esophagitis, gastritis, ulceration of the gastrointestinal mucosa), it is recommended to take it during the day with plenty of fluid and food.

The tablet can also be dissolved in a glass of water, stirring until completely dissolved.

Due to the possible development of photosensitivity, it is necessary to limit sun exposure during treatment and for 4-5 days after it.

With prolonged use, periodic monitoring of liver function and hematopoietic organs is necessary.

It may mask the manifestations of syphilis, therefore, in case of possible mixed infection, monthly serological testing is necessary for 4 months.

All tetracyclines form stable complexes with calcium ions in any bone-forming tissue. In this regard, intake during the period of tooth development can cause long-term staining of teeth in a yellow-gray-brown color, as well as enamel hypoplasia.

A false increase in urinary catecholamine levels may occur when determined by the fluorescent method. When examining thyroid gland biopsy specimens from patients who have received Doxycycline for a long time, dark brown staining of the tissue in microslides may be observed without impairment of its function.

When the dose is increased above 4 g, the pharmacokinetics of doxycycline become dose-independent and the blood concentration does not increase.

Effect on the ability to drive vehicles and operate machinery

The drug does not affect concentration, speed of mental and motor reactions.

Overdose

There is no information regarding acute doxycycline poisoning in humans. In case of overdose and the occurrence of any complaints, it is necessary to immediately stop taking the drug and take measures aimed at rapid elimination of the not yet absorbed drug from the body or reducing its absorption from the digestive tract (gastric lavage, intake of activated charcoal – if consciousness is preserved).

Treatment for overdose is primarily symptomatic and consists of monitoring and maintaining basic vital functions.

Doxycycline is not removed from the body by hemodialysis.

Drug Interactions

Absorption is reduced by antacids containing aluminum, magnesium, calcium ions, iron preparations, sodium bicarbonate, magnesium-containing laxatives, cholestyramine and colestipol, so their use should be separated by an interval of 3 hours.

Due to the suppression of intestinal microflora, it reduces the prothrombin index, which requires dose adjustment of indirect anticoagulants.

When combined with bactericidal antibiotics that disrupt cell wall synthesis (penicillins, cephalosporins), the effectiveness of the latter is reduced.

It reduces the reliability of contraception and increases the frequency of breakthrough bleeding while taking estrogen-containing oral contraceptives.

Ethanol, barbiturates, rifampicin, carbamazepine, phenytoin and other stimulators of microsomal oxidation, by accelerating the metabolism of doxycycline, reduce its plasma concentration.

Concomitant use of retinol promotes an increase in intracranial pressure.

Storage Conditions

The drug should be stored at a temperature not exceeding 25°C (77°F). Keep out of the reach of children.

Shelf Life

The shelf life is 5 years. Do not use the drug after the expiration date printed on the package.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.