Aminosalicylic acid - instructions for use, dose, side effects, contraindications

4-Aminosalicylic acid (not to be confused with 5-aminosalicylic acid, widely used in the treatment of non-infectious inflammatory bowel diseases!), Being an analogue of PABA, suppresses the growth and reproduction of Mycobacterium tuberculosis by competitive inhibition of folic acid formation. Weakly affects intracellular pathogens.When used in monotherapy, resistance develops rapidly.

Pharmacological effects

Antimycobacterial (bacteriostatic).

Spectrum of antimicrobial activity

It is active only against Mycobacterium tuberculosis (to a lesser extent in comparison with other anti-tuberculosis drugs), it does not affect other mycobacteria.

Pharmacokinetics:

Quickly and well absorbed from the digestive tract. Relationship with plasma proteins: 50-70% - aminosalicylic acid, 15% - sodium salt. Distribution: in most body fluids and tissues, especially in pleural effusion, caseous tissue; in CSF penetrates only with inflammation of the membranes of the brain. Biotransformation in the liver (50% dose) by acetylation to inactive metabolites. TCmax 1-4 h. T1 / 2 ~ 1 h. The total clearance depends on the metabolic rate and on excretion by the kidneys. Elimination by the kidneys - more than 80% within 24 hours, 50% or more in the form of metabolites.

Indications:

Tuberculosis (various forms and localization, as second-line therapy, in combination with other anti-tuberculosis drugs).

ICD-10

I.A15-A19.A15 Tuberculosis of respiratory organs, confirmed bacteriologically and histologically

I.A15-A19.A18 Tuberculosis of other organs

Contraindications:

Hypersensitivity.Renal failure (when trying to lower the dose, the therapeutic concentration in the plasma is not achieved). Carefully! Hepatic insufficiency, peptic ulcer of stomach and duodenum, deficiency of G-6-FD, CHF, pregnancy and lactation.

Carefully:

Application in pregnancy and lactation

Possible use in pregnancy in the event that the expected benefit of therapy for the mother exceeds the potential risk to the fetus. If necessary, use during lactation should stop breastfeeding.

Application for violations of liver function

Contraindicated in violations of liver function, hepatic insufficiency, hepatitis, liver cirrhosis.

During treatment with the drug it is necessary to monitor the function of the liver.

Application for violations of kidney function

Contraindicated in violations of kidney function, kidney failure, nephritis of nontuberculous etiology.

During treatment, urine tests should be performed regularly. The development of proteinuria and hematuria requires a temporary reversal of therapy.

Pregnancy and lactation:

Pregnancy

The category of FDA recommendations is not defined.The use is not recommended due to the effect on the gastrointestinal tract; In addition, one study showed that due to the use of I trimester, congenital anomalies of development may increase, although in other studies this has not been confirmed. With the complex therapy of tuberculosis with other drugs - the number of malformations of the ears, limbs, hypospadias increases.

Lactation

Penetrates into breast milk in small amounts (3 hours after ingestion of 4 g, the concentration was 1.1 μg / ml).

Dosing and Administration:

Inside (0.5-1 hour after meals, washed with water or milk, alkaline mineral water, weak (0.5-2%) sodium bicarbonate solution), 93-122, 3 g / day in 3-4 doses (in outpatient practice - once a day); for malnourished patients with a body weight of less than 50 kg - 6 g / day.

With concomitant diseases of the gastrointestinal tract, the initial forms of amyloidosis, the maximum daily dose of 4-6 g.

The granules are taken in teaspoons, taking into account the fact that 6 g of granules containing a spoon contain 2 g of aminosalicylic acid and 4 g of sugar (taking 1-2 teaspoons 3 times a day, the patient receives 6 or 12 g of active substance).

Patients who receive uncoated tablets cause gastrointestinal disorders, it is recommended to prescribe the drug in the form of granules or tablets,coated.

Use in children

Tuberculosis (various forms and localization - as second-line therapy in combination with other anti-tuberculosis drugs).

Inside 0.2 g / kg / day (maximum - 10 g / day) in 3-4 divided doses.

With tuberculosis, the spine was used for 18 months in combination with isoniazid, 18 months - as part of a combination therapy with isoniazid, streptomycin (3 months), surgical treatment; with pulmonary tuberculosis - 12 months in combination with isoniazid (18 months) and streptomycin (3 months); in combination with isoniazid - 18-24 months.

Tuberculosis of the lungs, treatment - isoniazid + thioacetazone comparable in effectiveness with isoniazid + aminosalicylic acid.

Side effects:

Hematologic: thrombocytopenia, leukopenia, B12-deficient megaloblastic anemia, hemolytic anemia (with deficiency of G-6-PD). On the part of the digestive tract (may be severe and require discontinuation; violation of the digestive tract function can cause malabsorption of cyanocobalamin, folate, lipids, can be divided daily dose into several times, taking with food or antacids for better portability, the children tolerated better than in adults) : decreased appetite, nausea, vomiting, flatulence, abdominal pain, diarrhea, constipation.

From the side of the nervous system - psychosis. Hypersensitivity (5-10% of adult patients, usually in the first few weeks of treatment): fever, dermatitis, eosinophilia, arthralgia, lymphadenopathy, bronchospasm, a syndrome resembling infectious mononucleosis.

Other: hepatosplenomegaly, jaundice, encephalitis, drug-induced hepatitis (0.32% of patients), hypothyroidism (with prolonged use in high doses), goitre (with prolonged use in high doses), myxedema (with prolonged use in high doses). Changes in laboratory indicators: increased activity of hepatic transaminases, hyperbilirubinemia, proteinuria or hematuria (require a temporary discontinuation of the drug), crystalluria.

Overdose:

Not described. Treatment is symptomatic.

Interaction:

Aminobenzoates - more active than aminosalicylic acid, are absorbed by mycobacteria, preventing the bacteriostatic effect. Simultaneous use is not recommended.

Anticoagulants: coumarin or indanedione derivatives - an increase in the effect of anticoagulants, caused by a lesser amount of blood clotting in the liver. Correction of doses of anticoagulants is necessary.

Local anesthetics, esters PABK (procaine) - antagonism with aminosalicylic acid is possible.

Violates the absorption of rifampicin (should be taken at intervals of 6 hours), erythromycin and lincomycin.

Disrupts the assimilation of cyanocobalamin (increases the need for cyanocobalamin and the risk of anemia).

When combined with isoniazid increases its concentration in the blood.

Salicylates - possible summation of side effects.

Special instructions:

Decreased kidney function against tuberculous intoxication or a specific lesion is not a contraindication to the appointment.

Monitoring of hepatic transaminase activity.

In combination with diagnostic tests: it can influence the results of the test for glucosuria and urobilinogen using Elrich's reagent.

Aqueous solutions of aminosalicylates are unstable and should be used immediately after preparation. The solution or syrup of sodium aminosalicylate in sorbitol is destroyed particularly quickly. The color change of the solution is not a reliable indicator of the destruction of sodium aminosalicylate and only indicates the oxidation of m-aminophenol.

It is not represented in the United States Pharmacopeia.

Instructions

Aminosalicylic acid (Acidum aminosalicylicum)