Sodium para-aminosalicylate

General characteristics. Structure:

Active agent: aminosalicylate sodium dihydrate of 1000 mg.

Excipients (kernel): cellulose microcrystallic - 60,0 mg, silicon dioxide colloid - 5,0 mg, povidone (polyvinylpirrolidone) - 45,0 mg, calcium stearate of-10,0 mg.

Excipients (cover): the mix "Acryl-EZE WHITE 93A" (methacrylic acid and ethyl acrylate copolymer [1:1], talc, titanium dioxide, silicon dioxide colloid, Natrii hydrocarbonas, sodium lauryl sulfate) - 72,0 mg, triethyl citrate - 8,0 mg.

Pharmacological properties:

Pharmacodynamics. Has bacteriostatic action. The competition to para-aminobenzoic acid (PABK) for an active center of a digidropteroatsinteta-za - the enzyme turning PABK into dihydrofolic acid is the cornerstone of tuberculostatic action and inhibits synthesis of folic acid in a microbic cell and/or synthesis of components of a cell wall of microbacteria, reducing iron capture by the last. On tuberculostatic activity concedes to an isoniazid and streptomycin. Shows activity only concerning Mycobacterium tuberculosis (the minimum overwhelming concentration of in vitro of 1-5 mkg/ml). Affects the mycobacteria which are in a condition of active reproduction and practically does not affect mycobacteria in a rest stage. Poorly influences on the activator which is located intracellularly. Does not affect other mycobacteria. Primary stability meets seldom, secondary develops slowly. It is applied in a combination with other antitubercular medicines that slows down development of resistance to them. Renders irritant action on  a mucous  membrane  of digestive tract.

Pharmako kinetics. Absorption from digestive tract - bystry and high. Easily gets through gistogematichesky barriers and it is distributed in fabrics. Reaches high concentration in caseous masses. Moderately gets into cerebrospinal fluid (only at an inflammation of a meninx). The maximum concentration (Stakh) after reception in a dose of 4 g - 75 mkg/ml. Communication with proteins of plasma - 50-60%. The main way of metabolism - acetylation. Are metabolized in a liver (more than 50% are acetylated to inactive metabolites) and partially in a stomach. 80% are removed by kidneys by glomerular filtering within 10 hours (50% - in the form of acetylized derivative). The general clearance depends both on metabolism speed, and on removal by kidneys. An elimination half-life (T1/2) at normal function of kidneys - 30-60 minutes, at a chronic renal failure - till 23 o'clock. Gets into breast milk.

 

Indications to use:

Tuberculosis of various forms and localizations (in a complex with other antitubercular medicines), including at multiple medicinal resistance to other antitubercular medicines.

Route of administration and doses:

Inside, in 0,5-1 h after food, washing down with water, milk, alkaline mineral water, 0,5-2% Natrii hydrocarbonas solution. The adult - on 9-12 g/days (3-4 g 3 times a day); the exhausted adult patient (with body weight less than 50 kg) - 6 g/days in 3-4 receptions. To children - at the rate of 0,2 g/kg/days in 3-4 receptions (a daily dose no more than 10 g).  In the conditions of  out-patient  treatment  it is possible to appoint all daily dose in one step, at bad portability - in 2 receptions. At associated diseases  of digestive tract and initial forms of an amyloidosis the maximum daily dose - 4-6 g/days. The quantity of courses and the general duration of treatment are defined individually.

Features of use:

Apply in a combination with more active antitubercular medicines.
In the course of treatment it is recommended to investigate systematically urine and blood, to control activity of "hepatic" transaminases. Depression of function of kidneys against the background of tubercular intoxication or specific tubercular defeat are not a contraindication to use. Development of a proteinuria and hamaturia demands temporary drug withdrawal. At the first signs indicating allergic reaction, administration of drug should be stopped and carried out the desensibilizing therapy.

INFLUENCE ON ABILITY TO DRIVING OF MOTOR TRANSPORT AND TO CONTROL OF MECHANISMS
Aminosalicylic  acid    does not influence  ability  to  driving  of motor transport  and  performance of work,  demanding  the increased speed of psychomotor reactions.

Side effects:

- From the alimentary system: decrease or loss of appetite, the increased salivation, nausea, vomiting, a meteorism, an abdominal pain, diarrhea  or  a lock;  increase  in activity of "hepatic" transaminases, hyperbilirubinemia, jaundice; seldom - medicinal hepatitis (including with a lethal outcome).
- From bodies of a hemopoiesis: seldom - thrombocytopenia, a leukopenia (up to an agranulocytosis), B12-scarce anemia, hemolitic anemia with positive test of Koombs.
- From urinogenital system: proteinuria, hamaturia, crystalluria.
- Allergic  reactions:  rash  (a small tortoiseshell, a purpura,  an enantema, exfoliative dermatitis, the syndrome     reminding     an infectious mononucleosis    or    a lymphoma),    fever, a bronchospasm, an arthralgia, an eosinophilia.
- Other: in high doses - anti-thyroid action;   at  prolonged  use goitrogenic  effect,  a medicinal  hypothyroidism,  a myxedema;  a pericardis,  a hypoglycemia, an optic neuritis    ,  encephalopathy, Leffler's syndrome (eosinophilic pneumonia, the migrating  pulmonary  infiltrate), a vasculitis, decrease in a prothrombin.

Interaction with other medicines:

Let's combine with other antitubercular medicines. Slows down emergence of resistance to an isoniazid and streptomycin. At combined use with an isoniazid increases its concentration in blood owing to the competition for the general ways of metabolism. Breaks absorption and reduces efficiency of rifampicin, erythromycin and linkomitsnn. Breaks digestion of cyanocobalamine (possibly development of B12-scarce anemia). Reduces concentration of digoxin in blood by 40%. Antiacid means do not break absorption
drug. Strengthens effect of indirect antikoagulyatn - derivatives of coumarin and an indandion (dose adjustment of anticoagulants is required). At  use   of iodinated  hormones of a thyroid gland, their analogs and antagonists (including anti-thyroid means) it is necessary to consider that against the background of para-aminobenzoic acid (PABK) concentration of thyroxine (T4) and thyritropic hormone (TTG) in blood changes.
Ammonium chloride increases risk of development of a crystalluria. The concomitant use with Etioniamidum increases risk of a hepatotoxic.
Difengidramin reduces efficiency of aminosalicylic acid. Probenetsid reduces excretion of aminosalicylic acid, increasing its concentration in plasma.

Contraindications:

Hypersensitivity, renal failure, liver failure, hepatitis, cirrhosis; amyloidosis of internals,
peptic ulcer of a stomach and 12-perstny gut, coloenteritis (aggravation), myxedema (noncompensated), nephrite, dekompensirovanny chronic heart failure (including against the background of heart disease), thrombophlebitis, hypocoagulation, epilepsy, children's age to Zkh of years.

WITH CARE
Moderately expressed liver failure, deficit glyukozo-6-fosfatdegidro-genazy, the compensated hypothyroidism.

PREGNANCY AND the PERIOD of the LACTATION Use of drug during pregnancy is admissible only if the possible advantage  of  treatment  for  mother  exceeds potential risk for a fruit. In the period of a lactation it is necessary to resolve an issue of the termination of breastfeeding for the period of treatment by drug.

Overdose:

Symptoms: strengthening of dozozavisimy side effects is possible.

Treatment: drug withdrawal, symptomatic therapy.

Storage conditions:

To store in the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

The tablets covered with a kishechnorastvorimy cover of 1000 mg.
On 100, 200, 300, 400, 500, 1000 tablets (for hospitals) in bank from polypropylene or to bank from polyethylene of low pressure with a cover from polypropylene or polyethylene of high pressure or to bank from polyethyleneterephthalate for medicines with a cover screw with control of the first opening. On 3, 4, 5, 6, 7, 8, 9, 10, 12, 15 cans together with the corresponding number of application instructions place in a group container.