Sodium aminosalicylate

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT SODIUM AMINOSALICYLATE

Composition:

Active substance: 1.0 g of granules contains 0.8 g of sodium aminosalicylate dihydrate;

Excipients: white crystalline sugar, corn starch, methacrylic acid copolymer dispersion, talc, titanium dioxide (E 171), propylene glycol, yellow dye FCF (E 110).

Pharmaceutical form. Enteric granules.

Main physicochemical properties: granules in the form of microspheres of regular and irregular shape, orange-colored.

Pharmacotherapeutic group. Antituberculosis agents. Aminosalicylic acid and its derivatives. ATC code J04A A02.

Pharmacological properties.

Pharmacodynamics.

The active ingredient of the medicinal product is sodium aminosalicylate. The drug has bacteriostatic activity against Mycobacterium tuberculosis.

In terms of antituberculosis activity, the drug is less effective than isoniazid and streptomycin; therefore, it is combined with other more potent antituberculosis agents (isoniazid and other hydrazides of isonicotinic acid, cycloserine, kanamycin).

Combination therapy delays the development of drug resistance and enhances the efficacy of antituberculosis drugs.

In high doses, the drug exerts antithyroid effects.

Pharmacokinetics.

When administered orally, the drug is well absorbed and penetrates into blood plasma and tissues of internal organs.

It is metabolized mainly in the liver within 30–60 minutes after administration, where acetylation and conjugation with glycine occur. Within one day, 90–100% of the administered dose is excreted in the urine.

Clinical characteristics.

Indications.

Active progressive forms of tuberculosis, primarily chronic fibrocavitary pulmonary tuberculosis.

Contraindications.

Hypersensitivity to any component of the drug or to salicylates. Severe renal (nephritis) or hepatic (hepatitis, cirrhosis) pathology, amyloidosis, peptic ulcer disease, cardiac decompensation, marked left ventricular myocardial hypertrophy, hypofunction of the thyroid gland, myxedema. Pregnancy and lactation. Children with body weight under 10 kg (due to difficulty in dosing the drug).

Interaction with other medicinal products and other forms of interactions.

When treating tuberculosis, several drugs with different mechanisms of action against Mycobacterium tuberculosis should be used simultaneously.

Sodium aminosalicylate is combined with other, more effective antituberculosis agents (isoniazid or other hydrazides of isonicotinic acid, cycloserine, kanamycin).

Combination therapy slows the development of mycobacterial resistance and results in mutual enhancement of drug effects.

The action of sodium aminosalicylate is enhanced when used concomitantly with barbiturates, streptomycin, and phenylbutazone. When used in combination with isoniazid, antituberculosis activity is enhanced due to increased plasma levels of isoniazid, but hemolytic anemia may occur. Probenecid delays excretion of the drug in urine, thereby increasing its plasma concentration and increasing the risk of toxicity (dose adjustment is required).

The efficacy of sodium aminosalicylate is reduced when used concomitantly with aminobenzoates and diphenhydramine.

Concomitant use with ethionamide increases the risk of hepatotoxicity. Diphenhydramine reduces the efficacy of aminosalicylic acid.

When used concomitantly with anticoagulants, the anticoagulant effect is enhanced because sodium aminosalicylate inhibits prothrombin synthesis in the liver.

Interaction of sodium aminosalicylate with hypoglycemic agents results in enhanced hypoglycemic effect.

Interaction of sodium aminosalicylate with capreomycin or use of high doses of the drug in elderly patients with peripheral edema and arterial hypertension may lead to the development of hypokalemia.

Ammonium chloride increases the risk of crystalluria.

When iodine-containing thyroid hormones, their analogs and antagonists (including antithyroid agents) are used, it should be noted that para-aminosalicylic acid alters the blood concentrations of T4 and TSH.

The effect of aminophenazone is enhanced when combined with sodium aminosalicylate.

Impairs vitamin B12 absorption, potentially leading to anemia and avitaminosis. In such cases, parenteral administration of vitamin B12 is recommended.

Impairs absorption of rifampicin, erythromycin, and lincomycin; when used concomitantly with isoniazid, increases its blood concentration; reduces digoxin blood concentration by 40%.

Adverse effects of the drug and salicylates are additive.

Antacid agents do not interfere with drug absorption.

Special precautions for use.

Use with caution in patients with impaired liver and kidney function, and in those with heart failure (use is contraindicated in severe cases).

Use with caution in patients with severe atherosclerosis and thrombophlebitis.

The drug should be used cautiously in patients with gastrointestinal disorders.

If signs of hepatitis occur, sodium aminosalicylate should be replaced with ethambutol.

Sodium aminosalicylate may impair blood coagulation.

Use with caution in patients with potential risk of bleeding of various origins.

Due to the risk of developing haemolytic anaemia, use with caution in patients with glucose-6-phosphate dehydrogenase deficiency.

Prolonged use of high doses of the drug, as well as its use in combination with ethionamide, may lead to decreased thyroid function. Hypothyroidism can be managed with replacement therapy using levothyroxine without discontinuing anti-tuberculosis treatment. This should be taken into account if a patient with tuberculosis develops hypofunction of the thyroid gland.

Crystalluria may develop during treatment with sodium aminosalicylate. Its formation is slowed down when urine pH is neutral or alkaline.

Sodium aminosalicylate is not recommended for patients on a low-sodium diet.

Smoking and alcohol consumption are prohibited during treatment.

During therapy, periodic laboratory monitoring of blood, urine, and liver function is required.

If signs of hepatitis occur, sodium aminosalicylate should be replaced with ethambutol.

If a patient has known intolerance to certain sugars, they should consult a physician before taking this medicinal product.

The dye Sunset Yellow FCF (E 110) may cause allergic reactions.

In case of allergic reactions, consult a physician regarding discontinuation of the drug.

Use during pregnancy or breastfeeding.

Use during pregnancy or breastfeeding is contraindicated.

Ability to influence reaction speed while driving or operating machinery.

The medicinal product does not affect reaction speed while driving or operating machinery. However, individuals who develop symptoms of hepatic encephalopathy during treatment should refrain from activities requiring rapid psychomotor responses.

Method of Administration and Dosage

The medication should be taken 30 minutes to 1 hour after eating, washed down with milk or mineral water.

A dosing device of 5 g with graduations is provided in the package (the dosing device holds 4 g of active substance).

For children with body weight from 10 kg to 40 kg, the dosage is 200 mg of the active substance per 1 kg of body weight per day. The daily dose should be divided into 3–4 administrations.

For children with body weight over 40 kg and adults: 5 g of the medication twice daily.

In cases of poor tolerance, the dosage should be reduced.

The duration of treatment depends on the nature and course of the disease.

Minimum treatment course: 3–5 months.

If necessary, the course may be extended.

Children

Due to the complexity of dosing, the medication should not be administered to children with body weight below 10 kg.

Overdose

Symptoms: nausea, vomiting, diarrhea; psychosis or exacerbation of adverse reactions may develop.

Treatment: administer activated charcoal to delay absorption. Prescribe antihistamines, calcium chloride, ascorbic acid; in cases of prolonged allergic reactions – corticosteroids.

Depending on the nature and severity of allergic manifestations, administration of the medication should be temporarily or completely discontinued.

Adverse Reactions.

Central nervous system: headache, dizziness, hepatic encephalopathy, including confusion, drowsiness.

Eye disorders: optic neuritis.

Blood and lymphatic system disorders: neutropenia, leukopenia, hemolytic anemia (in patients with glucose-6-phosphate dehydrogenase deficiency), impaired prothrombin synthesis, thrombocytopenia, agranulocytosis, eosinophilia. Hematomas and phlebitis may also occur.

Immune system disorders: hypersensitivity reactions, including fever; bronchospasm; asthmatic symptoms; pulmonary eosinophilic infiltrate/eosinophilic pneumonia; Löffler’s syndrome, joint pain, toxic-allergic reactions. In case of allergic manifestations, antihistamines, calcium chloride, ascorbic acid are prescribed; corticosteroids are used for prolonged allergic reactions.

Endocrine system disorders: hypothyroidism, hyperglycemia (with prolonged use of high doses).

Cardiovascular system disorders: pericarditis, vasculitis, fluctuations in blood pressure.

Gastrointestinal disorders: worsening and loss of appetite/anorexia, flatulence, dyspepsia, nausea, vomiting, epigastric/abdominal pain, diarrhea, constipation, metallic taste in the mouth.

If such adverse reactions occur, reduce the dose or temporarily discontinue the drug.

Adverse reactions are less pronounced if the patient adheres to a proper three-meal-a-day diet.

Hepatobiliary disorders: jaundice, hepatitis, hepatomegaly, liver tenderness, increased activity of "liver" transaminases.

Renal and urinary disorders: crystalluria.

Skin and subcutaneous tissue disorders: skin rashes, pruritus, dermatitis, urticaria, purpura, exanthema, enanthema, exfoliative dermatitis.

Musculoskeletal and connective tissue disorders: arthralgia, myalgia.

Metabolism and nutrition disorders: hypokalemia (with prolonged use in patients with cardiovascular diseases), calcium and phosphorus imbalance due to impaired vitamin D metabolism.

Shelf life. 3 years.

Storage conditions.

In original packaging at a temperature not exceeding 25°C. Keep out of reach of children.

Packaging.

100 g granules in a sachet; one sachet with a dosing device in a container.

Prescription status. Prescription only.

Manufacturer.

PJSC "Tekhnolog".

Manufacturer's address and location of its operations.

8 Stara Prorezna Street, Uman, Cherkasy Oblast, 20300, Ukraine.

INSTRUCTION
for medical use of medicinal product

SODIUM AMINOSALICYLATE

(SODIUM AMINOSALICYLATE)

Composition:

Active ingredient: 1.0 g granules contain 0.8 g sodium aminosalicylate dihydrate;

Excipients: crystalline white sugar, corn starch, methacrylate copolymer dispersion, talc, titanium dioxide (E 171), propylene glycol, sunset yellow FCF dye (E 110).

Pharmaceutical form. Enteric-soluble granules.

Main physicochemical properties: granules in the form of microspheres of regular and irregular shape, orange-colored.

Pharmacotherapeutic group. Antituberculosis agents. Aminosalicylic acid and its derivatives. ATC code J04AA02.

Pharmacological properties.

Pharmacodynamics.

The active substance of the medicinal product is sodium aminosalicylate. The drug has bacteriostatic activity against Mycobacterium tuberculosis.

In terms of antituberculosis activity, the drug is less effective than isoniazid and streptomycin; therefore, it is used in combination with other more potent antituberculosis agents (isoniazid and other isonicotinic acid hydrazide derivatives, cycloserine, kanamycin).

Combination therapy delays the development of drug resistance and enhances the antituberculosis effect.

In high doses, the drug exhibits antithyroid activity.

Pharmacokinetics.
After oral administration, the drug is well absorbed and penetrates into blood serum and internal organ tissues.

It is metabolized mainly in the liver within 30–60 minutes after intake, where acetylation and conjugation with glycine occur. Within 24 hours, 90–100% of the administered dose is excreted in urine.

Clinical characteristics.

Indications.

Active progressive forms of tuberculosis, primarily chronic fibro-cavitary pulmonary tuberculosis.

Contraindications.

Hypersensitivity to any component of the drug or to salicylates.

Severe renal pathology (nephritis), liver disorders (hepatitis, cirrhosis), amyloidosis, peptic ulcer disease, cardiac decompensation, marked left ventricular myocardial hypertrophy, hypofunction of the thyroid gland, myxedema. Pregnancy and breastfeeding. Children with body weight below 10 kg (due to difficulty in dosing).

Interaction with other medicinal products and other types of interactions.

For tuberculosis treatment, several drugs with different mechanisms of action against Mycobacterium tuberculosis should be used simultaneously.

Sodium aminosalicylate is combined with other, more effective antituberculosis drugs (isoniazid or other isonicotinic acid hydrazide derivatives, cycloserine, kanamycin).

Combination therapy slows the development of mycobacterial resistance and enhances mutual drug effects.

The effect of sodium aminosalicylate is enhanced when used concomitantly with barbiturates, streptomycin, and butadione. Combined use with isoniazid enhances antituberculosis activity due to increased plasma levels, but hemolytic anemia may occur.

Probenecid delays urinary excretion of the drug, increasing its plasma concentration and risk of toxicity (dose adjustment is required).

The efficacy of sodium aminosalicylate is reduced when used concomitantly with aminobenzoates and dimedrol.

Concomitant use with ethionamide increases the risk of hepatotoxicity. Diphenhydramine reduces the efficacy of aminosalicylic acid.

When used with anticoagulants, anticoagulant effects are enhanced because sodium aminosalicylate inhibits hepatic prothrombin synthesis.

Interaction with hypoglycemic agents may potentiate hypoglycemia.

Interaction of sodium aminosalicylate with capreomycin or use of high doses in elderly patients with peripheral edema and arterial hypertension may lead to hypokalemia.

Ammonium chloride increases the risk of crystalluria.

When thyroid hormones, their analogs and antagonists (including antithyroid agents) are used, it should be considered that serum concentrations of T4 and TSH may change under the influence of para-aminosalicylic acid.

Combination of sodium aminosalicylate with aminophenazone enhances the latter's effect.

The drug impairs vitamin B12 absorption, potentially leading to anemia and avitaminosis. In such cases, parenteral vitamin B12 is recommended.

It reduces absorption of rifampicin, erythromycin, and lincomycin; increases isoniazid plasma concentration when used concomitantly; reduces digoxin plasma concentration by 40%.

Adverse effects of the drug and salicylates are additive.

Antacid agents do not interfere with drug absorption.

Special precautions.

Use with caution in patients with impaired liver or kidney function, or heart failure (contraindicated in severe cases).

Use with caution in patients with severe atherosclerosis and thrombophlebitis.

The drug should be used cautiously in patients with gastrointestinal disorders.

In case of signs of hepatitis, sodium aminosalicylate should be replaced with ethambutol.

Sodium aminosalicylate may impair blood coagulation.

Use with caution in patients at risk of bleeding of various origins.

Due to the risk of hemolytic anemia, use with caution in patients with glucose-6-phosphate dehydrogenase deficiency.

Prolonged use of high doses, especially in combination with ethionamide, may cause decreased thyroid function. Hypothyroidism can be managed with levothyroxine replacement therapy without discontinuing antituberculosis treatment. This should be considered if hypothyroidism is observed in a tuberculosis patient.

Crystalluria may develop during sodium aminosalicylate therapy. Crystallization is slowed in neutral or alkaline urine (pH).

Sodium aminosalicylate is not recommended for patients on a low-sodium diet.

Smoking and alcohol consumption are prohibited during treatment.

Liver function, blood, and urine tests should be monitored during therapy.

If signs of hepatitis occur, sodium aminosalicylate should be replaced with ethambutol.

Patients with known sugar intolerance should consult a physician before taking this medicinal product.

Sunset yellow FCF dye (E 110) may cause allergic reactions.

In case of allergic manifestations, consult a physician regarding discontinuation of the drug.

Use during pregnancy or breastfeeding.

Use during pregnancy or breastfeeding is contraindicated.

Effect on ability to drive or operate machinery.

The drug does not affect reaction speed when driving or operating machinery. However, patients who develop symptoms of hepatic encephalopathy during treatment should avoid activities requiring rapid psychomotor responses.

Dosage and administration.

The drug should be taken 30 or 60 minutes after meals, with milk or mineral water.

A 5 g dosing device with markings is supplied with the package (the dosing device contains 4 g of active ingredient).

For children weighing 10 to 40 kg: 200 mg of active ingredient per kg of body weight daily, divided into 3–4 doses.

For children over 40 kg and adults: 5 g of the drug twice daily.

If the drug is poorly tolerated, the dose should be reduced.

Treatment duration depends on the nature and course of the disease.

Minimum treatment duration is 3–5 months.

The course may be extended if necessary.

Children.

Due to difficulty in dosing, the drug is not prescribed to children with body weight below 10 kg.

Overdose.

Symptoms: nausea, vomiting, diarrhea, psychosis, or exacerbation of adverse reactions.

Treatment: activated charcoal to delay absorption. Antihistamines, calcium chloride, ascorbic acid should be administered; corticosteroids are indicated for prolonged allergic reactions.

Depending on the nature and severity of allergic manifestations, drug administration should be temporarily or permanently discontinued.

Adverse reactions.

Nervous system disorders: headache, dizziness, hepatic encephalopathy, including confusion, drowsiness.

Eye disorders: optic neuritis.

Blood and lymphatic system disorders: neutropenia, leukopenia, hemolytic anemia (in patients with glucose-6-phosphate dehydrogenase deficiency), impaired prothrombin synthesis, thrombocytopenia, agranulocytosis, eosinophilia. Hematomas and phlebitis may occur.

Immune system disorders: hypersensitivity reactions, including fever; bronchospasm; asthmatic symptoms; pulmonary eosinophilic infiltrate/eosinophilic pneumonia; Löffler’s syndrome, joint pain, toxic-allergic reactions. In case of allergic manifestations, antihistamines, calcium chloride, ascorbic acid are prescribed; corticosteroids are used for prolonged allergic reactions.

Endocrine system disorders: hypothyroidism (with prolonged use of high doses), hyperglycemia.

Cardiovascular disorders: pericarditis, vasculitis, fluctuations in blood pressure.

Gastrointestinal disorders: worsening and loss of appetite/anorexia, flatulence, dyspepsia, nausea, vomiting, epigastric/abdominal pain, diarrhea, constipation, metallic taste in the mouth. If such adverse reactions occur, reduce the dose or temporarily discontinue the drug.

Adverse reactions are less pronounced if the patient adheres to a proper three-meal-a-day diet.

Hepatobiliary disorders: jaundice, hepatitis, hepatomegaly, liver tenderness, increased activity of "liver" transaminases.

Renal and urinary disorders: crystalluria.

Skin and subcutaneous tissue disorders: skin rashes, pruritus, dermatitis, urticaria, purpura, exanthema, enanthema, exfoliative dermatitis.

Musculoskeletal and connective tissue disorders: arthralgia, myalgia.

Metabolism and nutrition disorders: hypokalemia (with prolonged use in patients with cardiovascular diseases), calcium and phosphorus imbalance due to impaired vitamin D metabolism.

Shelf life. 3 years.

Storage conditions.

In original packaging at a temperature not exceeding 25°C. Keep out of reach of children.

Packaging.

100 g granules in a sachet; one sachet with a dosing device in a container.

Prescription status. Prescription only.

Manufacturer.

JSC "Tekhnolog".

Manufacturer's address and location of its operations.

8 Stara Prorezna Street, Uman, Cherkasy Oblast, 20300, Ukraine.