SULFADIMETHOXINE

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SULFADIMETHOXINE (SULFADIMETHOXINE)

Composition:

Active substance: sulfadimethoxine;

1 tablet contains sulfadimethoxine – 500 mg (0.5 g);

Excipients: potato starch, calcium stearate, colloidal anhydrous silicon dioxide, gelatin.

Pharmaceutical form. Tablets.

Main physicochemical properties: tablets of white or white with yellowish tint color, with flat surface, scored line and beveled edges.

Pharmacotherapeutic group.

Antimicrobial agents for systemic use. Long-acting sulfonamide.

ATC code J01ED01.

Pharmacological Properties.

Pharmacodynamics.

Sulfadimethoxine is a broad-spectrum antimicrobial bacteriostatic agent containing sulfonamide of prolonged action—sulfadimethoxine. It possesses antimicrobial properties. Active against gram-positive and gram-negative microorganisms: Staphylococcus spp., Streptococcus spp., including Streptococcus pneumoniae, Friedländer's bacillus, Escherichia coli, Shigella spp., Chlamydia trachomatis.

The mechanism of action is due 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.

It is not effective against bacterial strains resistant to other sulfonamide drugs.

Pharmacokinetics.

When administered orally, it is absorbed relatively slowly in the gastrointestinal tract. After single therapeutic dose intake (1–2 g), it appears in the blood within 30 minutes; however, maximum concentration is reached within 8–12 hours.

It penetrates through the placenta but, compared to other sulfonamides, penetrates poorly through the blood-brain barrier; therefore, its use in purulent meningitis is not advisable. Therapeutic concentration in adults is achieved when administered at doses of 1–2 g on the first day and 0.5–1 g on subsequent days.

It is excreted from the body mainly in the form of metabolites, primarily with urine. Elimination half-life is 16 hours.

Clinical characteristics.

Indications.

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

Contraindications.

Increased individual sensitivity to the components of the drug; history of severe toxic-allergic reactions to sulfonamides; bone marrow hematopoiesis suppression; renal and/or hepatic insufficiency; decompensated chronic heart failure; glucose-6-phosphate dehydrogenase deficiency; porphyria; azotemia; agranulocytosis; hemolytic anemia; drug-induced jaundice; severe dermatitis.

Interaction with other medicinal products and other types of interactions.

When used concurrently:

• with nonsteroidal anti-inflammatory drugs, sulfonylurea derivatives, antithrombotic agents, vitamin K antagonists – the effect of these drugs is enhanced;
• with folic acid, bactericidal antibiotics (including penicillins, cephalosporins) – the efficacy of sulfadimethoxine is reduced;
• with bactericidal antibiotics, oral contraceptives – the action of these drugs is reduced;
• with PAS (para-aminosalicylic acid) and barbiturates – the activity of sulfadimethoxine is enhanced;
• with pyrazolone derivatives, indomethacin, and salicylates – the activity and toxicity of sulfadimethoxine are increased;
• with methotrexate and phenytoin – the toxicity of sulfadimethoxine is increased;
• with erythromycin, lincomycin, tetracycline – mutual enhancement of antibacterial activity and broadening of the spectrum of action;
• with rifampicin, streptomycin, monomycin, kanamycin, gentamicin, oxichinoline derivatives (nitroxoline) – antibacterial action of the drugs remains unchanged;
• with nalidixic acid (negramon) – antagonism may occasionally occur;
• with chloramphenicol, nitrofurans – reduction of total effect.

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

Special precautions for use.

During treatment with the drug, regular monitoring of kidney function, peripheral blood parameters, and blood glucose levels is required.

Sulfonamides, including sulfadimethoxine, should not be used for the treatment of infections caused by group A beta-hemolytic streptococcus, as they do not eradicate this pathogen and therefore cannot prevent complications such as rheumatic fever and glomerulonephritis.

The drug should be prescribed with caution to patients with chronic heart failure, liver disorders, or impaired kidney function. Sulfadimethoxine should be administered cautiously to patients with severe forms of allergic diseases or bronchial asthma. Sulfonamides, including sulfadimethoxine, should be used with caution in patients with diabetes mellitus, as sulfonamides may affect blood glucose levels. During treatment, regular monitoring of blood glucose levels is necessary.

Since sulfonamides are bacteriostatic rather than bactericidal agents, a full course of therapy is required to prevent infection relapse and the development of resistant microbial strains.

Patients should consume sufficient fluids to prevent crystalluria and the development of urolithiasis.

The drug should be avoided in patients aged 65 years and older due to an increased risk of developing severe adverse reactions.

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

During treatment with the drug, 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.

Use during pregnancy or breastfeeding.

The drug is contraindicated during pregnancy and breastfeeding.

Ability to influence reaction speed when driving or operating machinery.

There is no available information regarding the effect of the drug on the ability to drive vehicles or operate machinery.

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

Dosage and Administration

Administer orally once daily with an interval of 24 hours between doses.

Adults: On the first day, administer 1–2 g of sulfadimethoxine (2–4 tablets); in subsequent days, 0.5–1 g of sulfadimethoxine (1–2 tablets) daily.

Children aged 12 years: On the first day, administer 1 g of sulfadimethoxine (2 tablets); in subsequent days, 0.5 g of sulfadimethoxine (1 tablet) daily.

Children aged 3 to 12 years: Administer sulfadimethoxine at a dosage of 25 mg/kg* body weight on the first day and 12.5 mg/kg* body weight daily in subsequent days.

After normalization of body temperature, continue the drug 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.

* Use in appropriate dosing.

Children. The drug is indicated for children aged 3 years and older.

Overdose.

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

Treatment: Discontinue the drug. If necessary, induce vomiting, perform gastric lavage, administer activated charcoal, cleansing enema, 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

Neurological disorders: headache, neurological reactions including aseptic meningitis, ataxia, mild intracranial hypertension, seizures, dizziness, somnolence/insomnia, fatigue, depression, peripheral or optic neuropathies, psychosis.

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.

Respiratory system disorders: pulmonary infiltrates, fibrosing alveolitis.

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

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

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

Allergic reactions: 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.

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

Other: myocarditis, nodular periarteritis, hypothyroidism, hypoglycemia.

Shelf life. 5 years.

Do not use after the expiry date stated on the packaging.

Storage conditions.

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

Keep out of the reach of children.

Packaging.

10 tablets in blisters.

10 tablets in blisters; 2 blisters per cardboard pack.

Prescription category.

Prescription only.

Manufacturer.

JSC "CHEMICAL PHARMACEUTICAL PLANT "CHERVONA ZIRKA".

Manufacturer's address and place of business.

1, Gordienkivska Street, Kharkiv, Kharkiv region, 61010, Ukraine.