Biseptol suspension 240mg / 5ml, 80ml

• Respiratory tract infections (acute and chronic bronchitis, bronchiectasis, croupous pneumonia, bronchopneumonia, pneumocystis pneumonia, pleural empyema, lung abscess),

• infections of ENT organs (otitis media, sinusitis, laryngitis, tonsillitis, pharyngitis, tonsillitis), scarlet fever,

• infections of the genitourinary organs (pyelonephritis, pyelitis, epididymitis, cystitis, urethritis, salpingitis, prostatitis, gonorrhea in men and women, chancre, lymphogranuloma venereal, inguinal granuloma),

• gastrointestinal tract infections (dysentery, cholera, typhoid fever, salmonella, paratyphoid fever, cholecystitis, cholangitis, gastroenteritis caused by enterotoxic strains of E. coli),

• infections of the skin and soft tissues (acne, furunculosis, pyoderma, abscess, wound infections),

• osteomyelitis (acute and chronic),

• brucellosis (acute),

• sepsis,

• peritonitis,

• meningitis,

• brain abscess

• osteoarticular infections,

• South American blastomycosis,

• malaria,

• whooping cough (as part of complex therapy).

Inside, after eating with a sufficient amount of liquid.

Adults and children over 12 years old: 960 mg every 12 hours;

in severe infections - 1440 mg every 12 hours;

with urinary tract infection - 10-14 days, with exacerbation of chronic bronchitis - 14 days, with travelers' diarrhea and shigellosis - 5 days. The minimum dose and dose for long-term treatment (more than 14 days) is 480 mg every 12 hours.

Children: from 2 months (or 6 weeks at birth from mothers with HIV infection) to 5 months - 120 mg each, from 6 months to 5 years - 240 mg each, from 6 to 12 years old - 480 mg every 12 hours, which approximately corresponds to a dose of 36 mg / kg per day. The course of treatment for urinary tract infections and acute otitis media - 10 days, shigellosis - 5 days. For severe infections, the dose for children can be increased by 50%.

In acute infections, the minimum duration of treatment is 5 days; after the disappearance of symptoms, therapy is continued for 2 days. If, after 7 days of therapy, clinical improvement does not occur, the patient's condition should be re-evaluated for possible correction of treatment. Chancre 960 mg every 12 hours; if after 7 days the healing of the skin element does not occur, you can extend the therapy for another 7 days. However, the lack of effect may indicate the resistance of the pathogen.

For women with acute uncomplicated urinary tract infections, a single dose of 1920-2880 mg is recommended, if possible in the evening after meals or before bedtime.

In pneumonia caused by Pneumocystis carinii - 30 mg / kg 4 times / day with an interval of 6 hours for 14-21 days.

For the prevention of pneumonia caused by Pneumocystis carinii, adults and children over 12 years old - 960 mg / day.

For children under 12 years old - 450 mg / m2 every 12 hours, for 3 consecutive days every week. The total daily dose should not exceed 1920 mg. In this case, you can use the following guidelines: for 0.26 m2 of body surface - 120 mg, respectively, for 0.53 m2 - 240 mg, for 1.06 m2 - 480 mg.

For other bacterial infections, the dose is selected individually depending on age, body weight, renal function and the severity of the disease, for example, with nocardiosis in adults - 2880-3840 mg / day for at least 3 months (sometimes up to 18 months). The course of treatment for acute brucellosis is 3-4 weeks, with typhoid and paratyphoid fever - 1-3 months.

Suspension for oral administration is white or light cream in color, with a strawberry smell.

100 ml

sulfamethoxazole 4 g

trimethoprim 0.8 g

Excipients: macrogol glyceryl hydroxystearate, magnesium aluminosilicate, sodium carmellose, citric acid monohydrate, methyl parahydroxybenzoate, propyl parahydroxybenzoate, sodium saccharinate, sodium hydrogen phosphate dodecahydrate, liquid maltitol, strawberry flavor, propylene glycol.

• Hepatic and / or renal failure (creatinine clearance less than 15 ml / min);

• aplastic anemia, B12-deficiency anemia,

• agranulocytosis,

• leukopenia;

• deficiency of glucose-6-phosphate dehydrogenase;

• simultaneous reception with dofetilide;

• lactation period; children's age up to 2 months or up to 6 weeks at birth from a mother with HIV infection;

• hypersensitivity to sulfonamides, trimethoprim and / or to other components of the drug.

• With care: thyroid dysfunction, history of severe allergic reactions, bronchial asthma, folic acid deficiency, porphyria, pregnancy.

pharmachologic effect

Co-trimoxazole is a combined antimicrobial drug consisting of sulfamethoxazole and trimethoprim in a 5: 1 ratio. Sulfamethoxazole, which is structurally similar to para-aminobenzoic acid (PABA), disrupts the synthesis of dihydrofolic acid in bacterial cells, preventing the incorporation of PABA into its molecule. Trimethoprim enhances the effect of sulfamethoxazole, disrupting the reduction of dihydrofolic acid to tetrahydrofolic acid, the active form of folic acid, which is responsible for protein metabolism and microbial cell division. Both components, therefore, disrupt the formation of folic acid, which is necessary for the synthesis of purine compounds by microorganisms, and then nucleic acids (RNA and DNA). This disrupts the formation of proteins and leads to the death of bacteria. In vitro is a broad-spectrum bactericidal preparation,however, the sensitivity may vary depending on geographic location. Typically sensitive pathogens (minimum inhibitory concentration (MIC) less than 80 mg / l for sulfamethoxazole): Moraxella (Branhamella) catarrhalis, Haemophilus influenzae (beta-lactamase-forming and beta-lactamase-forming strains), Haemophilus parainfluen coli, including Escherbacteriosis strains spp. (including Citrobacter freundii), Klebsiella spp. (including Klebsiella pneumoniae, Klebsiella oxytoca), Enterobacter cloaceae, Enterobacter aerogenes, Hafnia alvei, Serratia spp. (including Serratia marcescens, Serratia liquefaciens), Proteus mirabilis, Proteus vulgaris, Morganella morganii. Shigella spp. (including Shigella flexneri. Shigella sonnet). Yersinia spp. (including Yersinia enterocolitica), Vibrio cholerae, Edwardsiella tarda,Alcaligenes faecalis, Burkholderia (Pseudomonas) cepacia, Burkholderia (Pseudomonas) pseudomallei.

Also, Brucella spp .. Listeria monocytogenes, Nocardia asteroides, Pneumocystis carinii, Cyclospora cayetanensis can be sensitive. Partially sensitive pathogens (IPC 80-160 mg / l for sulfamethoxazole): coagulase-negative strains of Staphylococcus spp. (including methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus). Streptococcus pneumoniae (penicillin-susceptible and penicillin-resistant strains), Haemophilus ducreyi, Providencia spp. (including Providencia rettgeri), Salmonella typhi. Salmonella enteritidis, Slenotrdphomonas maltophilia (formerly Xanthomonas maltophilia), Acinetobacter Iwoffii, Acinetobacter baumanii, Aeromonas hydrophila. Resistant pathogens (IPC more than 160 mg / l for sulfamethoxazole): Mycoplasma spp., Mycobacterium tuberculosis, Treponema pallidum, Pseudomonas aeruginosa.If a drug is prescribed empirically, it is necessary to take into account the local characteristics of drug resistance of possible pathogens of a particular infectious disease.

For infections that can be caused by partially susceptible microorganisms, it is recommended to conduct a sensitivity test to exclude the resistance of the pathogen.

Pharmacokinetics

When taken orally, absorption is fast and almost complete - 90%. After a single dose of 160 mg of trimethoprim + 800 mg of sulfamethoxazole, the Cmax of trimethoprim is 1.5-3 ?g / ml, and of sulfamethoxazole - 40-80 ?g / ml. Cmax in blood plasma is reached after 1-4 hours; the therapeutic level of concentration is maintained for 7 hours after a single dose. With repeated administration with an interval of 12 hours, the minimum equilibrium concentrations are stabilized in the range of 1.3-2.8 ?g / ml for trimethoprim and 32-63 ?g / ml for sulfamethoxazole. The Css of the drug is reached within 2-3 days. It is well distributed in the body. Vd of trimethoprim is about 130 liters, sulfamethoxazole - about 20 liters. Penetrates the blood-brain barrier, placental barrier and into breast milk. In the lungs and urine, it creates concentrations exceeding the content in plasma. Trimethoprim is slightly betterhow sulfamethoxazole penetrates into non-inflamed prostate tissue, seminal fluid, vaginal secretions, - saliva, healthy and - inflamed lung tissue, bile, while both components of the drug penetrate into the cerebrospinal fluid and aqueous humor of the eye equally. Large amounts of trimethoprim and slightly smaller amounts of sulfamethoxazole enter the interstitial and other extravasal body fluids from the bloodstream, while the concentrations of trimethoprim and sulfamethoxazole exceed the MIC for most pathogenic microorganisms. Plasma protein binding - 66% for sulfamethoxazole, for trimethoprim - 45%. It is metabolized in the liver. Some metabolites have antimicrobial activity. Sulfamethoxazole is metabolized primarily by N4-acetylation and, to a lesser extent, by conjugation with glucuronic acid.It is excreted by the kidneys in the form of metabolites (80% within 72 hours) and unchanged (20% sulfamethoxazole, 50% trimethoprim); a small amount - through the intestines. Both substances, as well as their metabolites, are excreted by the kidneys, both by glomerular filtration and tubular secretion, as a result of which the concentration of both active substances in the urine is much higher than in the blood. T1 / 2 of sulfamethoxazole - 9-11 hours, trimethoprim - 10-12 hours, in children - significantly less and depends on age: up to 1 year - 7-8 hours, 1-10 years - 5-6 hours. / or patients with impaired renal function (creatinine clearance (CC) 15-20 ml / min) T1 / 2 increases, which requires dose adjustment.as well as their metabolites, are excreted by the kidneys, both by glomerular filtration and tubular secretion, as a result of which the concentration of both active substances in the urine is much higher than in the blood. T1 / 2 of sulfamethoxazole - 9-11 hours, trimethoprim - 10-12 hours, in children - significantly less and depends on age: up to 1 year - 7-8 hours, 1-10 years - 5-6 hours. / or patients with impaired renal function (creatinine clearance (CC) 15-20 ml / min) T1 / 2 increases, which requires dose adjustment.as well as their metabolites, are excreted by the kidneys, both by glomerular filtration and tubular secretion, as a result of which the concentration of both active substances in the urine is much higher than in the blood. T1 / 2 of sulfamethoxazole - 9-11 hours, trimethoprim - 10-12 hours, in children - significantly less and depends on age: up to 1 year - 7-8 hours, 1-10 years - 5-6 hours. / or patients with impaired renal function (creatinine clearance (CC) 15-20 ml / min) T1 / 2 increases, which requires dose adjustment.In elderly patients and / or patients with impaired renal function (creatinine clearance (CC) 15-20 ml / min) T1 / 2 increases, which requires dose adjustment.In elderly patients and / or patients with impaired renal function (creatinine clearance (CC) 15-20 ml / min) T1 / 2 increases, which requires dose adjustment.

Side effect

From the nervous system: headache, dizziness, aseptic meningitis, peripheral neuritis, convulsions, ataxia, ringing in the ears, depression, hallucinations, apathy, nervousness.

From the respiratory system: pulmonary infiltrates: eosinophilic infiltrate, allergic alveolitis (cough, shortness of breath).

On the part of the digestive system: nausea, vomiting, decreased appetite, diarrhea, gastritis, abdominal pain, glossitis, stomatitis, cholestasis, increased activity of hepatic transaminases, hepatitis (including cholestatic), hepatonecrosis, 'disappearing bile duct' syndrome ( ductopenia), hyperbilirubinemia, pseudomembranous colitis, acute pancreatitis.

From the side of hematopoiesis: leukopenia, neutropenia, thrombocytopenia, hypoprothrombinemia, agranulocytosis, anemia (megaloblastic, hemolytic / autoimmune or aplastic), methemoglobinemia, eosinophilia.

From the urinary system: interstitial nephritis, renal dysfunction, hematuria, increased blood urea, hypercreatininemia, toxic nephropathy with liguria and anuria, crystalluria.

From the musculoskeletal system: arthralgia, myalgia, rhabdomyolysis (mainly in AIDS patients).

Allergic reactions: fever, angioedema, pruritus, photosensitivity, skin rash, urticaria, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, allergic myocarditis, hyperektiva , sclera, anaphylactic / anaphylactoid reactions, serum sickness, hemorrhagic vasculitis (Schonlein-Henoch purpura), periarteritis nodosa, lupus-like syndrome.

Others: hyperkalemia (mainly in AIDS patients in the treatment of pneumocystis pneumonia), hyponatremia, hypoglycemia, weakness, fatigue, insomnia, candidiasis.

Application during pregnancy and lactation

During pregnancy, the drug should be prescribed only if the expected benefit from its use outweighs the possible risk to the fetus, since both trimethoprim and sulfamethoxazole penetrate the placental barrier and, thus, can affect the metabolism of folic acid. In late pregnancy, the use of the drug should be avoided due to the possible risk of developing kernicterus in newborns. Due to the fact that trimethoprim and sulfamethoxazole penetrate into breast milk, the use of co-trimaxozole during lactation is contraindicated. Pregnant women receiving the drug are advised to prescribe 5 mg of folic acid per day.

Application for violations of liver function

Contraindicated: liver failure.

Application for impaired renal function

Contraindicated: renal failure (creatinine clearance less than 15 ml / min).

Use in elderly patients

The duration of treatment should be as short as possible, especially in elderly and senile patients.

special instructions

Co-trimoxazole should be prescribed only in cases where the advantage of such combination therapy over other antibacterial monopreparations outweighs the possible risk. Since the sensitivity of bacteria to antibacterial drugs in vitro varies in different geographic areas and over time, local characteristics of bacterial sensitivity should be taken into account when choosing a drug. With long courses of treatment, regular blood tests are necessary, since there is a possibility of hematological changes (most often asymptomatic). These changes can be reversible with the appointment of folic acid (3-6 mg / day), which does not significantly violate the antimicrobial activity of the drug. Particular caution should be exercised when treating elderly patients or patients with suspected baseline folate deficiency.Folic acid administration is also advisable for long-term treatment in high doses. With a significant decrease in the number of any blood cells, the drug should be discontinued. It is also inappropriate during treatment to consume foods containing large amounts of PABA - green parts of plants (cauliflower, spinach, legumes), carrots, tomatoes. With long courses (especially with renal failure), it is necessary to regularly conduct a general urinalysis and monitor kidney function. For the prevention of crystalluria, it is recommended to maintain a sufficient volume of excreted urine. The likelihood of toxic and allergic complications of sulfonamides increases significantly with a decrease in the filtration function of the kidneys. At the first appearance of a skin rash or any other severe adverse reaction, the drug should be discontinued.In case of a sudden appearance or increase in cough or shortness of breath, the patient should be re-examined and the question of stopping the drug treatment should be considered. Excessive sun and ultraviolet radiation should be avoided. The risk of side effects is significantly higher in AIDS patients. It is not recommended for use in diseases caused by group A beta-hemolytic streptococcus, due to the widespread resistance of the strains. Cases of pancytopenia have been described in patients taking co-trimoxazole. Trimethoprim has a low affinity for human dehydrofolate reductase, but it can increase the toxicity of methotrexate, especially in the presence of other risk factors, such as old age, hypoalbuminemia, renal impairment, and bone marrow suppression. These side effects are more likely if methotrexate is given in high doses.For the prevention of myelosuppression, it is recommended to prescribe folic acid or calcium folinate to such patients. Trimethoprim interferes with phenylalanine metabolism, but this does not affect patients with phenylketonuria, provided that an appropriate diet is followed. Patients whose metabolism is characterized by 'slow acetylation', more The duration of treatment should be as short as possible, especially in elderly and senile patients. Co-trimoxazole and, in particular, its constituent trimethoprim can affect the results of determining the concentration of methotrexate in serum, carried out by the method of competitive binding to proteins using bacterial dihydrofolate reductase as a ligand. However, when determining methotrexate by radioimmunoassay, interference does not occur.Trimethoprim and sulfamethoxazole can affect the results of the Jaffe reaction (determination of creatinine by reaction with picric acid in an alkaline medium), while in the normal range the results are overestimated by about 10%.

Influence on the ability to drive vehicles and use mechanisms

Given the possibility of developing significant side effects, during the period of treatment, care must be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Overdose

Symptoms: nausea, vomiting, intestinal colic, dizziness, headache, drowsiness, depression, fainting, confusion, fever, hematuria, crystalluria; with prolonged overdose - thrombocytopenia, leukopenia, megaloblastic anemia, jaundice. Treatment: gastric lavage, forced diuresis, acidification of urine increases the excretion of trimethoprim, intramuscularly - 5-15 mg / day of calcium folinate (eliminates the effect of trimethoprim on the bone marrow), if necessary - hemodialysis.

Drug interactions

Increases the anticoagulant activity of indirect anticoagulants (dose adjustment of the anticoagulant), as well as the effect of hypoglycemic drugs and methotrexate (competes for protein binding and renal transport of methotrexate, increasing the concentration of free methotrexate). Reduces the intensity of hepatic metabolism of phenytoin (lengthens its T1 / 2 by 39%), enhancing its effect and toxicity. With the simultaneous use of co-trimoxazole with pyrimethamine in doses exceeding 25 mg / week, the risk of developing megaloblastic anemia increases. Diuretics (usually thiazides and in elderly patients) increase the risk of thrombocytopenia. May increase serum digoxin concentrations, especially in elderly patients, monitoring of serum digoxin concentrations is necessary.The effectiveness of tricyclic antidepressants in combination with co-trimoxazole may be reduced. Patients receiving co-trimoxazole and cyclosporine after kidney transplantation may experience a reversible deterioration in renal function, manifested by an increase in creatinine levels. Medicines that inhibit bone marrow hematopoiesis increase the risk of myelosuppression. With the combined use of co-trimoxazole with indomethacin, an increase in the concentration of sulfamethoxazole in the blood is possible. Described one case of toxic delirium after the simultaneous administration of co-trimoxazole and amantadine. With simultaneous use with ACE inhibitors, especially in elderly patients, hyperkalemia may develop. Trimethoprim, inhibiting the transport system of the kidneys, increases the AUC of dofetilide by 103% and Cmax of dofetilide by 93%.When the concentration is increased, dofetilide can cause ventricular arrhythmias with prolongation of the QT interval, including pirouette-type arrhythmias. The simultaneous administration of dofetilide and trimethoprim is contraindicated.