Pas

INSTRUCTIONS for medical use of the medicinal product PAS (PAS)

Composition:

active substance: sodium aminosalicylate;

100 g of granules contain 80 g of sodium aminosalicylate;

excipients: colloidal anhydrous silicon dioxide, povidone, microcrystalline cellulose, maize starch, talc, dried pineapple flavour, tartrazine (E 102).

Pharmaceutical form. Enteric-coated granules.

Main physico-chemical properties: enteric-coated granules of light yellow to yellow colour.

Pharmacotherapeutic group. Antituberculosis agents. ATC code J04A A02.

Pharmacological Properties.

Pharmacodynamics.

The active ingredient of the drug 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 primarily 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. Severe renal pathology (nephritis), liver disease (hepatitis, cirrhosis), amyloidosis, peptic ulcer disease, cardiac decompensation, marked left ventricular myocardial hypertrophy, hypofunction of the thyroid gland, myxedema.

Interaction with other medicinal products and other forms of interaction.

When treating tuberculosis, several drugs with different mechanisms of action against Mycobacterium tuberculosis should be used simultaneously. Combination therapy slows the development of bacterial resistance and results in mutual enhancement of drug effects.

Sodium aminosalicylate slows the development of resistance of Mycobacterium tuberculosis to isoniazid and streptomycin. When used in combination with isoniazid, there is a risk of developing hemolytic anemia.

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

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

Probenecid (a uricosuric agent) delays the urinary excretion of the drug, resulting in increased plasma concentration of sodium aminosalicylate and an increased risk of toxicity (dose adjustment is required).

Sodium aminosalicylate may cause impaired absorption of vitamin B₁₂ and lead to avitaminosis. In such cases, parenteral administration of vitamin B₁₂ is recommended.

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 hypokalemia.

The drug interferes with absorption and reduces the effectiveness of rifampicin, erythromycin, and lincomycin; when used concomitantly with isoniazid, it increases isoniazid's blood concentration; it reduces digoxin blood concentration by 40%.

Antacid agents do not interfere with drug absorption.

When iodine-containing thyroid hormones, their analogs, and antagonists (including antithyroid agents) are used, it should be noted that during PAS therapy, serum concentrations of T₄ and TSH may change. Ammonium chloride increases the risk of crystalluria. Concurrent use with ethionamide increases the risk of hepatotoxicity. Diphenhydramine reduces the efficacy of aminosalicylic acid.

Adverse effects of the drug and salicylates are additive in nature.

Special precautions for use.

The drug should be prescribed with caution to patients with gastrointestinal disorders, hepatic or renal dysfunction, and in cases of heart failure (in severe disorders, the use of the drug is contraindicated).

Use with caution in patients with severe atherosclerosis and thrombophlebitis.

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

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 levothyroxine replacement therapy without discontinuing antituberculosis treatment. This should be taken into account if a tuberculosis patient develops hypofunction of the thyroid gland.

Crystalluria may develop during the use of sodium aminosalicylate. Crystal formation is slowed under neutral or alkaline urine pH conditions.

Use of sodium aminosalicylate may impair blood coagulation. Use with caution in patients at potential risk of hemorrhage of various origins.

Due to the risk of developing hemolytic anemia, the drug should be used with caution in patients with glucose-6-phosphate dehydrogenase deficiency.

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

Periodically perform blood and urine analyses and monitor liver function parameters.

Smoking and alcohol consumption are prohibited during treatment.

The medicinal product contains the dye tartrazine (E 102), which may cause allergic reactions.

Use during pregnancy or breastfeeding.

The use of the drug is contraindicated during pregnancy or breastfeeding.

Ability to influence reaction speed when driving or operating machinery.

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

Method of Administration and Dosage

The medication should be taken 0.5 to 1 hour after a meal, washed down with milk or mineral water.

The package includes 1 measuring spoon of 5 g with graduations (1 measuring spoon contains 4 g of active substance).

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

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.

The minimum treatment course is 3–5 months.

If necessary, the course may be extended.

Children. Due to the complexity of dosing, the medication should not be used for treating children with body weight less than 10 kg.

Overdose

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

Treatment is symptomatic. Administer activated charcoal to delay absorption, perform gastric lavage, ensure monitoring of vital functions, and provide symptomatic therapy.

Adverse Reactions.

From the nervous system: headache, dizziness, hepatic encephalopathy, including confusion and somnolence.

Visual disturbances: optic neuritis.

From the hematopoietic and lymphatic systems: neutropenia, leukopenia, thrombocytopenia, agranulocytosis, impaired prothrombin synthesis, vitamin B12-deficiency megaloblastic anemia, hemolytic anemia (in patients with glucose-6-phosphate dehydrogenase deficiency) with positive Coombs test.

From the immune system: hypersensitivity reactions, including fever; bronchospasm; asthmatic symptoms; eosinophilic lung infiltrate/eosinophilic pneumonia; Löffler’s syndrome.

From the endocrine system: hypothyroidism with prolonged use of high doses.

From the cardiovascular system: pericarditis, vasculitis.

From the gastrointestinal tract: worsening and loss of appetite/anorexia, flatulence, dyspepsia, nausea, vomiting, epigastric or 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-times-daily meal regimen.

Hepatic and/or biliary function disorders: increased liver transaminase activity, hyperbilirubinemia, onset of pain and enlargement of the liver, hepatosplenomegaly, jaundice, hepatitis (including fatal cases).

Renal and urinary tract disorders: crystalluria.

From the skin and subcutaneous tissues: skin rashes, pruritus, dermatitis, urticaria, purpura, exanthema, enanthema, exfoliative dermatitis.

From the musculoskeletal and connective tissue: arthralgia, myalgia.

Metabolic and nutritional disorders: hypokalemia (with prolonged use in patients with cardiovascular diseases).

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

Shelf life: 3 years.

Storage conditions: Store in the original packaging, in a place inaccessible to children, at a temperature not exceeding 25°C.

Packaging: 100 g of granules in an aluminum foil sachet, placed in a polyethylene pouch, together with a silica gel desiccant packet, a measuring spoon, and instructions, all contained in a plastic container.

Prescription status: Prescription only.

Manufacturer: Vivimed Labs Ltd, India.

Manufacturer’s address and site of operations:
D-125 & 128, Phase-III, IDA, Jeedimetla, Medchal-Malkajgiri District – 500055, India.