Paser (Granules) Instructions for Use

Marketing Authorization Holder

Jacobus Pharmaceutical Company, Inc. (USA)

ATC Code

J04AA01 (Aminosalicylic acid)

Active Substance

Aminosalicylic acid (USP)

Dosage Form

Paser

Prolonged-release granules for oral use 4 g/1 sachet: 6.48 g sachets 30 pcs.

Dosage Form, Packaging, and Composition

Excipients: microcrystalline cellulose – 1.28 g, hypromellose 2906 – 0.05 g, Eudragit L-30D – 0.7 g, talc – 0.35 g, hypromellose (E-5) – 0.03 g, colloidal silicon dioxide – 0.005 g.

6.48 g – sachets (30) – cardboard packs.

Clinical-Pharmacological Group

Antituberculosis drug

Pharmacotherapeutic Group

Antitubercular agent

Pharmacological Action

Antituberculosis agent. Aminosalicylic acid (para-Aminosalicylic acid; PAS) exerts a bacteriostatic effect. The basis of the tuberculostatic action is the competition with PABA for the active site of dihydropteroate synthase, an enzyme that converts PABA into dihydrofolic acid, and it inhibits the synthesis of folic acid in the microbial cell and/or the synthesis of components of the mycobacterial cell wall, reducing iron uptake by the latter. In terms of tuberculostatic activity, it is inferior to isoniazid and streptomycin.

It exhibits activity only against Mycobacterium tuberculosis (MIC in vitro 1-5 µg/ml). It acts on mycobacteria in the state of active multiplication and has practically no effect on mycobacteria in the dormant stage. It has a weak effect on the pathogen located intracellularly.

It does not act on other mycobacteria.

Primary resistance is rare, secondary resistance develops slowly.

It is used only in combination with other antituberculosis drugs, which slows down the development of resistance to them.

Pharmacokinetics

Aminosalicylic acid rapidly forms a toxic inactive metabolite in an acidic environment. The plasma T_1/2 is 1 hour. Plasma protein binding is about 50-60%. It is metabolized in the liver and partially in the stomach. 80% of aminosalicylic acid is excreted in the urine, with more than 50% in the acetylated form. The acetylation process is not genetically determined. Aminosalicylic acid is excreted by glomerular filtration. It penetrates into the cerebrospinal fluid only with inflammation of the meninges.

Indications

Tuberculosis of various forms and localizations (as part of combination therapy with other antituberculosis drugs), including in cases of multiple drug resistance to other antituberculosis drugs.

ICD codes

Dosage Regimen

The dose, number of courses, and total duration of treatment are determined individually.

It is administered intravenously as an infusion over 2-4 hours. If a longer infusion is required, it is recommended to maintain electrolyte balance by oral administration of potassium preparations or by adding them to the infusion solution.

The daily dose for adults and children over 14 years of age is 10-15 g. For premature newborns, infants, and children under 6 years of age, the daily dose is usually 200-300 mg/kg.

If long-term therapy is necessary, it is recommended to maintain electrolyte balance by oral administration of potassium preparations or by adding them to the infusion solution, based on the results of a preliminary assessment of plasma potassium levels.

Adverse Reactions

From the digestive system: frequently – increased salivation, nausea, vomiting, deterioration or loss of appetite, abdominal pain, diarrhea, flatulence, constipation; rarely – moderate transient increase in transaminase activity, sometimes accompanied by jaundice. Approximately 25% of patients with an allergic reaction to PAS develop liver damage, and in 10% of cases this can lead to liver failure and death.

Allergic reactions: fever, dermatitis of the urticarial or purpuric type, enanthema, asthmatic phenomena, joint pain, eosinophilia; rarely – angioedema, joint swelling, drug fever, reactions similar to lupus erythematosus, accompanied by damage to the spleen, liver, kidneys, gastrointestinal tract, bone marrow, and nervous system (e.g., radicular pain, meningism, erythema multiforme exudativum (Stevens-Johnson syndrome), Lyell’s syndrome.

From the hematopoietic system: rarely – agranulocytosis, leukopenia, thrombocytopenia, drug-induced hepatitis. Allergic reactions may appear after several days, although they mainly occur between the 2nd and 7th weeks of treatment (most often at the 4th-5th week).

From the blood coagulation system: in some cases with prolonged use – increased prothrombin time, accompanied by bleeding, and in exceptional cases – accompanied by hemorrhagic rash.

From the urinary system: with varying frequency (from rare to very frequent cases) – moderate transient microhematuria, albuminuria and cylindruria, increased blood urea levels (indicating a uremic reaction, especially in patients with impaired renal function and acidosis).

From the endocrine system: possible (especially with long-term use in high doses) – deterioration of thyroid function, hypothyroidism, goiter.

From metabolism: rarely – sharp disturbances in electrolyte balance, mainly in the form of hypokalemia when administered in high doses (especially in elderly patients with edema and arterial hypertension, as well as in patients with meningitis); when administered in high doses, acidosis is possible due to loss of cations (most often in children); rarely – normoglycemic or hyperglycemic glucosuria.

From the respiratory system: in some cases – pulmonary infiltrate (including allergic) (Löffler’s syndrome).

From the nervous system: in some cases – paralysis, clonic-tonic convulsions, psychosis.

Contraindications

Impaired renal function, renal failure, nephritis of non-tuberculous etiology, impaired liver function, hepatic failure, hepatitis, liver cirrhosis, decompensated heart failure, gastric and duodenal ulcer, inflammatory bowel diseases in the acute phase, decompensated myxedema, epilepsy, lactation period; hypersensitivity to aminosalicylic acid and other salicylates.

Use in Pregnancy and Lactation

Use during pregnancy is possible if the expected therapeutic benefit for the mother outweighs the potential risk to the fetus. If use during lactation is necessary, breastfeeding should be discontinued.

Use in Hepatic Impairment

Contraindicated in impaired liver function, hepatic failure, hepatitis, liver cirrhosis.

Liver function should be monitored during treatment with the drug.

Use in Renal Impairment

Contraindicated in impaired renal function, renal failure, nephritis of non-tuberculous etiology.

Urinalysis should be performed regularly during treatment. The development of proteinuria and hematuria requires temporary discontinuation of therapy.

Pediatric Use

Use is possible according to the dosage regimen.

Special Precautions

During treatment, blood and urine tests should be performed regularly, and liver function should be monitored.

The development of proteinuria and hematuria requires temporary discontinuation of therapy.

At the first symptoms of an allergic reaction, the use of aminosalicylic acid should be discontinued and desensitizing therapy should be carried out.

To prevent crystal formation, it is necessary to alkalinize the urine, especially if it has an acidic reaction.

Aminosalicylic acid should not be administered in the same solution with rifampicin and protionamide.

Drug Interactions

Aminosalicylic acid impairs the absorption of rifampicin, erythromycin, and lincomycin.

Aminosalicylic acid impairs the absorption of vitamin B₁₂, which may lead to the development of anemia.

With simultaneous use with isoniazid or phenytoin, the plasma residence time of isoniazid or phenytoin increases.

With simultaneous use with salicylates, phenylbutazone, or other anti-inflammatory drugs with high protein binding, the concentration and plasma residence time of aminosalicylic acid increase.

With simultaneous use with diphenhydramine, the plasma concentration of aminosalicylic acid decreases.

Aminosalicylic acid inhibits the absorption of folate and may enhance the toxicity of folate antagonists, including methotrexate.

Probenecid reduces the excretion of aminosalicylic acid, increasing its plasma concentration.

Storage Conditions

Store at 2°C (36°F) to 15°C (59°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.