Sulfadimethoxine-darnitsa

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT SULFADIMETHOXIN-DARNITSA (SULFADIMETHOXINE-DARNITSA)

Composition:

Active substance: sulfadimethoxine;

One tablet contains 500 mg of sulfadimethoxine;

Excipients: methylcellulose, microcrystalline cellulose, sodium croscarmellose, sodium lauryl sulfate, calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or white with creamish shade tablets, flat cylindrical shape, with beveled edges and a score line.

Pharmacotherapeutic group.

Antibacterial agents for systemic use. Long-acting sulfonamides. Sulfadimethoxine. ATC code J01ED01.

Pharmacological Properties.

Pharmacodynamics.

Antimicrobial bacteriostatic agent, a long-acting sulfonamide. Its mechanism of action is related to competitive antagonism with para-aminobenzoic acid, inhibition of dihydropteroate synthetase, and disruption of tetrahydrofolic acid synthesis, which is essential for the synthesis of purines and pyrimidines. Active against gram-positive and gram-negative microorganisms: Staphylococcus spp., Streptococcus spp., including Streptococcus pneumoniae, Friedländer's bacillus, Escherichia coli, Shigella spp., Chlamydia trachomatis.

Pharmacokinetics.

After oral administration, the drug is detectable in the blood within 30 minutes; the time to reach maximum plasma concentration (Tmax) is 8–12 hours. It poorly penetrates the blood-brain barrier. Therapeutic concentration in adults is achieved with a daily dose of 1–2 g on the first day and 0.5–1 g on subsequent days. Unlike other sulfonamides, in most cases metabolism occurs via microsomal glucuronidation associated with cytochrome P450 and NADPH (nicotinamide-adenine dinucleotide phosphate). The drug is primarily excreted in the urine. Elimination half-life (T1/2) is 16 hours.

Clinical characteristics.

Indications.

Infectious-inflammatory diseases caused by microflora sensitive to sulfadimethoxine: tonsillitis, bronchitis, pneumonia, sinusitis, otitis, dysentery, inflammatory diseases of biliary and urinary tracts, gonorrhea, pertussis, pyoderma, meningitis, wound infections, trachoma, toxoplasmosis, shigellosis, resistant forms of malaria (in combination with antimalarial agents).

Contraindications.

History of severe toxic-allergic reactions to sulfonamides, hypersensitivity to components of the drug, bone marrow hematopoiesis suppression, agranulocytosis, hemolytic anemia, renal and/or hepatic insufficiency, decompensated chronic heart failure, glucose-6-phosphate dehydrogenase deficiency, porphyria, azotemia, drug-induced urticaria, severe dermatitis.

Interaction with other medicinal products and other types of interactions.

Non-steroidal anti-inflammatory agents, sulfonylurea derivatives, antithrombotic agents, vitamin K antagonists – when used concomitantly, the effect of these drugs is enhanced.

Folic acid, bactericidal antibiotics (including penicillins, cephalosporins) – reduce the efficacy of sulfadimethoxine.

Bactericidal antibiotics, oral contraceptives – when used concomitantly, the effect of these drugs is reduced.

Para-aminosalicylic acid (PAS), barbiturates – when used in combination with these medicinal products, the activity of sulfadimethoxine is enhanced.

Pyrazolone derivatives, indomethacin, and salicylates – enhance the activity and toxicity of sulfadimethoxine.

Methotrexate and phenytoin – enhance the toxicity of sulfadimethoxine.

Erythromycin, lincomycin, tetracycline – when used concomitantly, mutual enhancement of antibacterial activity occurs, and the spectrum of action is broadened.

Rifampicin, streptomycin, monomycin, kanamycin, gentamicin, oxochinoline derivatives (nitroxoline) – when used concomitantly, antibacterial action of the drugs remains unchanged.

Nalidixic acid (negramon) – antagonism is sometimes observed.

Chloramphenicol, nitrofurans – reduced overall effect.

The drug should not be administered simultaneously with hexamethylenetetramine (urotropine), antidiabetic agents (sulfonylurea derivatives), phenytoin, neodicoumarin, and other indirect anticoagulants.

Special precautions for use

When using the medicinal product, it is necessary to systematically monitor kidney function, peripheral blood parameters, and blood glucose levels.

Sulfonamides, including sulfadimethoxine, must not be used to treat infections caused by group A beta-hemolytic streptococci, as they do not eradicate this pathogen and therefore cannot prevent complications such as rheumatic fever and glomerulonephritis.

The medicinal product must be administered with caution to patients with chronic heart failure, liver disorders, or impaired kidney function. Sulfadimethoxine should be prescribed with caution to patients with severe allergic diseases or bronchial asthma, as well as those with blood disorders. Sulfonamides, including sulfadimethoxine, should be used cautiously in patients with diabetes mellitus, as sulfonamides may affect blood glucose levels.

Since sulfonamides are bacteriostatic rather than bactericidal agents, a full course of therapy is required to prevent recurrence of infection and the development of resistant microbial strains. Patients should consume sufficient fluids to prevent crystalluria and the development of urolithiasis.

Administration of the medicinal product to patients aged 65 years and older should be avoided due to an increased risk of severe adverse reactions.

Exposure to direct sunlight and artificial ultraviolet radiation should be avoided due to the possibility of photosensitization during sulfonamide therapy.

During treatment with the medicinal product, the prescribed dosing regimen must be strictly followed, using the recommended dose at 24-hour intervals, without missing doses. If a dose is missed, the next dose should not be doubled.

Important information about excipients

This medicinal product contains sodium compounds. Caution is advised when administering to patients on a sodium-controlled diet.

Use during pregnancy or breastfeeding

The medicinal product is contraindicated during pregnancy and breastfeeding.

Ability to influence reaction rate when driving or operating machinery

Information regarding the effect of the medicinal product on the ability to drive or operate machinery is lacking.

Until the individual patient's response to the medicinal product is known, patients should refrain from driving or operating machinery, considering that adverse reactions of the nervous system such as dizziness, convulsions, ataxia, drowsiness, depression, and psychosis may occur during treatment with sulfadimethoxine.

Method of Administration and Dosage.

The medicinal product should be administered orally once daily with 24-hour intervals between doses.

Adults: On day 1, administer 1−2 g of sulfadimethoxine (2−4 tablets); on subsequent days, 500 mg–1 g of sulfadimethoxine (1−2 tablets) daily.

Children aged 12 years and older: On day 1, administer 1 g of sulfadimethoxine (2 tablets); on subsequent days, 500 mg of sulfadimethoxine (1 tablet) daily.

Children aged 3 to 12 years: Administer sulfadimethoxine at a dosage of 25 mg/kg body weight on day 1; on subsequent days, 12.5 mg/kg body weight daily.

After normalization of body temperature, continue treatment with the medicinal product at maintenance doses for another 2−3 days.

The duration of treatment depends on the nature and severity of the disease. On average, the treatment course lasts 7−14 days.

Children.

The medicinal product is indicated for children aged 3 years and older.

Overdose.

Symptoms: Thirst, dry mouth, anorexia, pain in the right subcostal area and lumbar region, spasmodic abdominal pain, nausea, vomiting, dizziness, headache, drowsiness, loss of consciousness, oliguria, change in urine color (intense yellow-brown color). Hyperthermia, hematuria, and crystalluria may occur. Biochemical analysis may reveal increased activity of liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase). Pathological blood changes (leukopenia, agranulocytosis, hemolytic anemia) and jaundice are later manifestations of overdose. Methemoglobinemia, tachycardia, paresthesia, dermatitis, diarrhea, and cholestasis may also develop.

Treatment: Discontinue administration of the medicinal product. If necessary, induce vomiting, perform gastric lavage, administer cleansing enema, activated charcoal, and alkaline drinks. In confirmed cases of methemoglobinemia, intravenous administration of 1% methylene blue is indicated. In severe cases, forced diuresis is recommended. Peritoneal dialysis is ineffective; hemodialysis is only moderately effective in treating sulfonamide overdose.

Adverse reactions.

Respiratory system, thoracic and mediastinal disorders: pulmonary infiltrates, fibrosing alveolitis.

Gastrointestinal disorders: thirst, dry mouth, dyspeptic symptoms, nausea, vomiting, diarrhea, anorexia, pancreatitis, pseudomembranous colitis.

Hepatobiliary disorders: increased liver enzyme activity (ALT, AST, alkaline phosphatase), cholestatic hepatitis, hepatonecrosis, hepatomegaly, jaundice.

Renal and urinary disorders: change in urine color (intense yellow-brown color), crystalluria; possible nephrotoxic reactions – interstitial nephritis, tubular necrosis, renal failure.

Nervous system and psychiatric disorders: headache, neurological reactions including aseptic meningitis, ataxia; mild intracranial hypotension, seizures, dizziness, somnolence/insomnia, fatigue, depression, peripheral or optic neuropathies, psychosis.

Blood and lymphatic system disorders: leucopenia, agranulocytosis, aplastic anemia, thrombocytopenia, hypoprothrombinemia, eosinophilia, hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency.

Immune system disorders: toxic epidermal necrolysis (Lyell's syndrome), Stevens–Johnson syndrome, systemic lupus erythematosus, serum sickness-like syndrome, anaphylactic reactions, swelling of the tongue, upper lip, swallowing difficulties.

Skin and subcutaneous tissue disorders: skin rashes, urticaria, allergic dermatitis, photosensitization, exfoliative dermatitis, nodular erythema.

General disorders: drug fever, pain in the right hypochondrium and lumbar region.

Other: myocarditis, polyarteritis nodosa, hypothyroidism, hypoglycemia.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after registration of the medicinal product is an important procedure. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.

Shelf life. 5 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in a blister pack; 1 blister pack in a carton; 10 tablets in blister packs.

Prescription category. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address and place of business.

13, Boryspilska Street, Kyiv, 02093, Ukraine.