Phthalylsulfatiazole - instructions for use, dose, side effects, contraindications

Antibacterial agent, a sulfonamide derivative. Has a wide spectrum of antimicrobial action. Phtalylsulfatiazole is active against Gram-positive and Gram-negative microorganisms, including pathogens of intestinal infections. Poorly absorbed from the digestive tract. Acts predominantly in the lumen of the intestine, where the sulfonamide part of the sulfatiazole molecule (norsulfazole) is gradually released.

The mechanism of action is associated with competitive antagonism with PABA and competitive inhibition of dihydropteroate synthetase, which leads to a disruption in the synthesis of tetrahydrofolic acid necessary for the synthesis of purines and pyrimidines.

Pharmacokinetics:After oral administration, it is practically not absorbed. In the small intestine under the influence of aminopeptidases gradually cleaves sulfatiazole, which, without having time to adsorb, provides high antimicrobial efficacy in intestinal infections.It is excreted mostly with feces. A small (absorbed) amount (5-10% of the dose) is evenly distributed in the body, acetylated in the liver and excreted in the urine.

Indications:Dysentery (acute and chronic in the acute stage), colitis, gastroenteritis; prevention of infectious complications in surgical interventions on the intestine.

ICD-10

I.A00-A09.A03.9 Shigellosis, unspecified

I.A00-A09.A09 Diarrhea and gastroenteritis of allegedly infectious origin

XI.K50-K52.K51 Ulcerative colitis

XXI.Z20-Z29.Z29.2 Another type of preventive chemotherapy

Contraindications:

Hypersensitivity to phthalylsulfatiazole and other sulfonamides; Hyperbilirubinemia (in children), deficiency of glucose-6-phosphate dehydrogenase (risk of hemolysis), severe renal and hepatic impairment, blood disorders, systemic lupus erythematosus, pregnancy, breast-feeding, neonatal period, infancy.

Diseases of the blood system, hyperthyroidism, glomerulonephritis, acute hepatitis, intestinal obstruction.

Carefully:Renal insufficiency (dose adjustment may be required), hepatic insufficiency, elderly age, bronchial asthma and other allergic reactions in the anamnesis, AIDS (tendency to adverse reactions).

Pregnancy and lactation:

Category of recommendations for FDA is not defined.

Qualitative and well-controlled studies on humans and animals have not been conducted. Some sulfonamides can cause embryonic abnormalities, including cleft palate in animals, but concerns about teratogenic effects in children seem unfounded. Sulfonamides are probably safe in the first trimester of pregnancy, although during pregnancy they should be used only in the absence of a suitable alternative treatment. Because of the possible replacement of indirect bilirubin and the risk of nuclear jaundice in newborns, sulfonamides should be avoided in the last trimester of pregnancy.

Penetrates into breast milk in low concentrations, for healthy children, the risk is insignificant. The risk of nuclear jaundice is higher for premature infants, children with various diseases and pathological conditions, children with hyperbilirubinemia, deficiency glucose-6-phosphate dehydrogenase.

Dosing and Administration:Inside. In acute dysentery, adults are prescribed 1-2 days, 6 g per day (every 4 hours - 1 g), 3-4 days - 4 g (every 6 hours - 1 g), in 5-6 days - 3 g per day (every 8 hours - 1 g). The average exchange dose is 25-30 g.After 5-6 days, the second cycle of treatment is carried out: 1-2 days - 1 g after 4 hours (at night - 8 hours), 3-4 days - 1 g after 4 hours (at night do not give) - 4 g in total day, day 5 - 3 g per day. The total dose in the second cycle is 21 grams, and in the light course - 18 g. Higher doses for adults: single dose - 2 g, daily - 7 g. Children under 3 years - 0.2 g / kg per day in 3 divided doses within 7 days; children older than 3 years - 0.4-0.75 g (depending on age) for admission 4 times a day. For other infections, adults in the first 2-3 days - 1-2 g every 4-6 h, and in the next 2-3 days - half the dose. Children are prescribed 0.1 g / kg per day in equal doses after 4 hours (with an overnight break), in the following days - 0.2-0.5 g every 6-8 hours.

Side effects:

Systemic side effects, characteristic of sulfonamides, are rare due to insignificant absorption.

From the side nervous system: headache, dizziness, depressed mood.

From the side of cardio-vascular system: myocarditis, cyanosis.

From the side system of blood: in rare cases - leukopenia, thrombocytopenia, agranulocytosis, hemolysis of erythrocytes. With prolonged use, anemia may occur due to a deficiency of pantothenic and pteroylglutaric acids produced by microbial cells.

From the side organs of the digestive tract: nausea, vomiting, diarrhea, lesions of the oral cavity (including stomatitis, gingivitis, glossitis), gastritis, cholangitis, hepatitis, insufficiency of B vitamins (due to oppression of the intestinal microflora).

From the side respiratory system: eosinophilic pneumonia.

From the side urinary system: urolithiasis disease.

Allergic and toxic-allergic reactions: drug allergy, including skin manifestations of drug allergy in the form of various rashes, up to nodular and multiform ekssidative erythema, in some cases - epidermal necrolysis (Lyell syndrome). In some cases, there is an allergic edema of the lips and face, nodular periarteritis.

Overdose:

Not described.

Treatment is symptomatic.

Interaction:

Myelotoxic drugs - increased hematotoxicity.

Some sulfonamides, when combined with cyclosporine, can reduce its plasma concentrations.

PASK and barbiturates: the activity of sulfonamides increases.

Salicylates - the activity increases.

Thioacetazone, levomycetin: the possibility of agranulocytosis increases.

Funds that acidify urine - increase the risk of developing crystalluria.

Nitrofurans: the risk of anemia and methemoglobinemia increases.

Oxacillin: decreases the activity of the antibiotic.

Sulfonamides can potentiate the effects of certain drugs, such as oral anticoagulants, methotrexate, phenytoin (this may occur due to the displacement of drugs from the bonds with proteins or the suppression of metabolism).

Combined use of phthalylsulfatiazole with acids and acid-binding agents, hexamethylenetetramine, adrenaline solution is not advisable, since they are chemically incompatible.

With the combined use of phthalylsulfatiazole with preparations containing PABA esters (novocaine, anesthesin, dicaine), the antibacterial activity of sulfanilamide is inactivated by a competitive mechanism. The effect is enhanced by antibiotics and well-absorbed sulfonamides.

Sulfanilamides in high doses can cause a hyperglycemic effect; The antidiabetic effect of sulfonylurea derivatives can be increased by sulfonamides.

Special instructions:

Malotoxic. Usually does not cause side effects.When treating gastrointestinal infections, it is usually used together with antibacterial drugs with high absorption.

To achieve adequate antibiotic prophylaxis in operations on the intestine, it is preferable to use parenteral antibacterial agents.

In order to prevent crystalluria during the period of treatment, it is necessary to drink plenty of liquids (2-3 times per day), the risk of crystalluria can be reduced by basifying urine.

When the rash appears, discontinue treatment because of the risk of developing serious allergic reactions like Stevens-Johnson syndrome.

It may be necessary to monitor blood and urine tests, especially with prolonged treatment.

All sulfonamides have a high degree of binding to proteins, each of them has a different ability to displace indirect bilirubin.

During the period of treatment it is recommended to take B vitamins.

Instructions

Phtalylsulfatiazole (Phthalylsulfathiazolum)