Biseptol - instructions for use, doses, side effects, contraindications

Excipients: macrogol glyceryl hydroxy stearate, magnesium aluminosilicate; carmellose sodium; citric acid monohydrate; methylparahydroxybenzoate; propyl parahydroxybenzoate; sodium saccharinate; sodium hydrophosphate dodecahydrate; maltitol; flavoringstrawberry; propylene glycol; purified water.

Description:Suspension of white or light cream color with strawberry odor.

Pharmacotherapeutic group:Antimicrobial agent combined.

ATX: & nbsp

J.01.E.E.01 Co-trimoxazole [sulfamethoxazole in combination with trimethoprim]

Pharmacodynamics:

Co-trimoxazole is a combined antimicrobial drug consisting of sulfamethoxazole and trimethoprim in a 5: 1 ratio.

Sulfamethoxazole, similar in structure to para-aminobenzoic acid (PABA), disrupts the synthesis of dihydrofolic acid in bacterial cells, preventing inclusion of PABA in its molecule.

Trimethoprim enhances the action of sulfamethoxazole, violating the restoring dihydrofolic acid to tetrahydrofolic - the active form of folic acid, responsible for protein metabolism and division of a microbial cell.

Both components, thus, violate the process of the formation of folic acid, necessary for the synthesis by microorganisms of purine compounds, and then of nucleic acids (RNA and DNA). This breaks the formation of proteins and leads to the death of bacteria.

In vitro is a broad-spectrum bactericidal drug,However, the sensitivity may depend on the geographical location.

Usually, sensitive pathogens (minimal inhibitory concentration (MIC) less than 80 mg / l for sulfamethoxazole): Moraxella (Branhamella) catarrhalis, Haemophilus influenzae (beta-lactamase-forming and beta-lactamase-forming strains), Haemophilus parainfluenzae, Escherichia coli (including entero-genotoxic strains), Citrobacter spp. (incl. Citrobacter freundii), Klebsiella spp. (incl. Klebsiella pneumoniae, Klebsiella oxytoca), Enterobacter cloaceae, Enterobacter aerogenes, Hajhia alvei, Serratia spp. (incl. Serratia marcescens, Serratia liquefaciens), Proteus mirabilis, Proteus vulgaris, Morganella morganii. Shigella spp. (incl. Shigella flexneri. Shigella sonnet), Yersinia spp. (incl. Yersinia enterocolitica), Vibrio cholerae, Edwardsiella tarda, Alcaligenes faecalis, Burkholderia (Pseudomonas) cepacia, Burkholderia (Pseudomonas) pseudomallei.

Also, there may be sensitive Brucella spp. Listeria monocytogenes, Nocardia asteroides, Pneumocystis carinii, Cyclospora cayetanensis.

Partially sensitive pathogens (MIC of 80-160 mg / l for sulfamethoxazole): coagulase negative strains Staphylococcus spp. (including methicillin-sensitive and methicillin-resistant strains Staphylococcus aureus). Streptococcus pneumonia (penicillin-sensitive and penicillin-resistant strains), Haemophilus ducreyi, Providencia spp. (incl. Providencia rettgeri), Salmonella typhi, Salmonella enteritidis, Stenotrophomonas maltophilia (previously called Xanthomonas maltophilia), Acinetobacter Iwoffii, Acinetobacter baumanii, Aeromonas hydrophila.

Stable pathogens (MIC of more than 160 mg / l for sulfamethoxazole): Mycoplasma spp., Mycobacterium tuberculosis, Treponema pallidum. Pseudomonas aeruginosa.

If the drug is prescribed empirically, it is necessary to take into account local characteristics of resistance to the drug of possible pathogens of a specific infectious disease.In infections that can be caused by partially sensitive microorganisms, it is recommended that the sample be tested for sensitivity in order to exclude the resistance of the pathogen.

Pharmacokinetics:

When taken orally, absorption is rapid and almost complete - 90%. After a single administration of 160 mg of trimethoprim + 800 mg of sulfamethoxazole, the maximum concentration (Cmah) of trimethoprim - 1.5-3 μg / ml, and sulfamethoxazole - 40-80 μg / ml. Stam in the blood plasma is reached in 1-4 hours; the therapeutic level of concentration persists for 7 hours after a single dose. With repeated administration with an interval of 12 hours, the minimum equilibrium concentrations (Css) stabilized in the range 1.3-2.8 μg / ml for trimethoprim and 32-63 μg / ml for sulfamethoxazole. Css the drug is achieved within 2-3 days.

Well distributed in the body. Volume of distribution (Vd) trimethoprim is about 130 liters, sulfamethoxazole - about 20 liters. Penetrates through the blood-brain barrier, placental barrier and into breast milk. In the lungs and urine creates concentrations exceeding the content in the plasma. Trimethoprim is somewhat better than sulfamethoxazole penetrates into the non-inflamed prostate tissue, seminal fluid, vaginal secretions, saliva, healthy and inflamed lung tissue, bile, while in the cerebrospinal fluid and watery eyes, both components of the drug penetrate equally. Large amounts of trimethoprim and slightly smaller amounts of sulfamethoxazole come from the bloodstream into the interstitial and other extravasal body fluids, with concentrations of trimethoprim and sulfamethoxazole exceeding the MIC for most pathogens.

The connection with plasma proteins is 66% in sulfamethoxazole, in trimethoprim 45%.

Metabolised in the liver. Some metabolites have antimicrobial activity. Sulfamethoxazole is metabolized predominantly by N4-acetylation and, to a lesser extent, 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 intestine.

Both substances, as well as their metabolites, are excreted by the kidneys, both by glomerular filtration and tubular secretion, so that the concentrations of both active substances in the urine are significantly higher than in the blood.

The half-life period (T1 / 2) of sulfamethoxazole is 9-11 h, trimethoprim is 10-12 h, in children it is much less and depends on the age: up to 1 year - 7-8 h, 1-10 years - 5-6 h.In elderly patients and / or patients with impaired renal function (creatinine clearance (CK) 15-20 ml / min) T1 / 2 increases, which requires dose adjustment.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to the preparation:

- infections of the respiratory tract: chronic bronchitis (exacerbation), pneumocystis

pneumonia (treatment and prevention) in adults and children;

- infection of the ENT organs: otitis media (in children);

- infections of the urino-genital organs: urinary tract infections, mild chancroid;

- gastrointestinal tract infections: typhoid fever, paratyphoid, shigellosis (caused by susceptible strains Shigella flexneri and Shigella sonnei); travelers diarrhea caused by enterotoxic strains Escherichia coli, Cholera (in addition to replenishment of fluid and electrolytes);

- other bacterial infections (possible combination with antibiotics): nocardiosis, brucellosis (acute), actinomycosis, osteomyelitis (acute and chronic), South American blastomycosis, toxoplasmosis (as part of complex therapy).

Contraindications:

- Hypersensitivity to sulfonamides, trimethoprim and / or to other components of the drug;

- hepatic and / or renal insufficiency (creatinine clearance less than 15 ml / min);

- aplastic anemia, B 12-deficiency anemia, agranulocytosis, leukopenia;

- deficiency of glucose-6-phosphate dehydrogenase;

- simultaneous reception with dofetilide;

- lactation period;

- children under 2 months of age or up to 6 weeks of age from a mother with HIV infection.

Carefully:Dysfunction of the thyroid gland, severe allergic reactions in history, bronchial asthma, deficiency of folic acid, porphyria, pregnancy.

Pregnancy and lactation:

In pregnancy, the drug should be given only if the expected benefit from its use exceeds the possible risk to the fetus, because both trimethoprim and sulfamethoxazole penetrate the placental barrier and, thus, can affect the exchange of folic acid.

In late pregnancy, the use of the drug should be avoided because of the possible risk of developing nuclear jaundice in newborns.

Due to the fact that trimethoprim and sulfamethoxazole penetrate into breast milk, the use of co-trimoxazole during the lactation period is contraindicated.

Pregnant women who receive the drug, it is recommended to appoint 5 mg of folic acid per day.

Dosing and Administration:

Inside, after eating with enough liquid.

Adults and children over 12 years of age: 960 mg every 12 hours; in severe infections - 1440 mg every 12 hours; with a 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) - 480 mg every 12 hours.

Children: from 2 months (or 6 weeks at birth from mothers with HIV infection) to 5 months - 120 mg, from 6 months to 5 years - 240 mg, from 6 to 12 years - 480 mg every 12 hours, which approximately corresponds to a dose of 36 mg / kg per day.

The course of treatment for infections of the urinary tract and acute otitis - 10 days, shigellosis - 5 days. In severe infections, doses 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 there is no clinical improvement, the patient's condition should be reassessed for possible correction of treatment.

Soft chancre - 960 mg every 12 hours; if after 7 days of healing of the skin element does not occur, you can extend the therapy for another 7 days. However, lack of effect may indicate resistance of the pathogen.

Women with acute uncomplicated urinary tract infections recommend a single dose of 1920-2880 mg, possibly in the evening after a meal or at bedtime ..

With pneumonia caused by Pneumocystis carinii - 30 mg / kg 4 times a 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 - 960 mg per day. For children under 12 years - 450 mg / sq. M 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: 0.26 square meters of the body surface - 120 mg, respectively, 0.53 square meters - 240 mg, 1.06 square meters - 480 mg.

In other bacterial infections, the dose is selected individually depending on the age, body weight, kidney function and severity of the disease, for example, in nocardiosis, adults - 2880-3840 mg / day for at least 3 months (sometimes up to 18 months).

The course of treatment for acute brucellosis - 3-4 weeks, with typhoid fever and paratyphoid - 1-3 months.

Side effects:

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, dyspnea).

From the side of the digestive system: nausea, vomiting, decreased appetite, diarrhea, gastritis, abdominal pain, glossitis, stomatitis, cholestasis, increased activity of "liver" transaminases, hepatitis (including cholestatic), hepatonecrosis, the syndrome of the "vanishing bile duct" (duktopenia), hyperbilirubinemia, pseudomembranous colitis, acute pancreatitis.

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

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

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

Allergic reactions: (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, allergic myocarditis, conjunctival hyperemia, sclera, hypertension, anaphylactic / anaphylactoid reactions, serum sickness, hemorrhagic vasculitis (purpura Shenlaine-Genocha), nodular periarteritis, lupus-like syndrome.

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

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,in / m - 5-15 mg / day calcium folinata (eliminates the effect of trimethoprim on the bone marrow), if necessary - hemodialysis.

Interaction:

Increases the anticoagulant activity of indirect anticoagulants (correction of the anticoagulant dose), 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 (prolongs its T1 / 2 by 39%), enhancing its effect and toxic effect.

With the simultaneous use of co-trimoxazole with pyrimethamine in doses exceeding 25 mg / week, the risk of megaloblastic anemia increases.

Diuretics (more often thiazides and in elderly patients) increase the risk of thrombocytopenia.

It may increase serum concentrations of digoxin, especially in elderly patients, it is necessary to monitor serum concentrations of digoxin.

The effectiveness of tricyclic antidepressants in combination with co-trimoxazole can be reduced.

In patients receiving co-trimoxazole and ciclosporin after a kidney transplant, there may be a reversible impairment of kidney function, manifested by an increase in the level of creatinine.

Drugs that inhibit bone marrow hematopoies increase the risk of myelosuppression.

When co-trimoxazole is combined with indomethacin, an increase in the concentration of sulfamethoxazole in the blood is possible.

One case of toxic delirium is described after simultaneous administration of co-trimoxazole and amantadine.

When used simultaneously with angiotensin-converting enzyme (ACE) inhibitors, especially in elderly patients, hyperkalemia may develop.

Trimethoprim, by inhibiting the kidney transport system, increases the area under the drug concentration-time curve (AUC) by 103% and Cm93% dofetilide. With an increase in concentration, dofetilide can cause ventricular arrhythmias with an interval lengthening Q-T, including arrhythmia of the "pirouette" type. The simultaneous administration of dofetilide and trimethoprim is contraindicated.

Special instructions:

Co-trimoxazole should be given only in cases where the advantage of such combination therapy over other antibacterial mono drugs exceeds the possible risk. Because the sensitivity of bacteria to antibacterial drugs in vitro changes in different geographical areas and in time, when choosing a drug, local peculiarities of bacterial sensitivity should be taken into account.

With long-term courses of treatment, regular blood tests are necessary, since there is a possibility of hematological changes (most often asymptomatic). These changes can be reversible in the appointment of folic acid (3-6 mg / day), which does not significantly violate the antimicrobial activity of the drug. Particular caution should be shown in the treatment of elderly patients or patients with a suspected initial lack of folate. The purpose of folic acid is also suitable for long-term treatment in high doses. With a significant reduction in the number of any blood cells, the drug should be discarded.

It is also inappropriate to use food products containing large quantities of PABC - green parts of plants (cauliflower, spinach, beans), carrots, tomatoes.

At long courses (especially at a renal failure), it is necessary to spend on a regular basis the general analysis of urine and to supervise function of kidneys.

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 significantly increases with a decrease in the filtration function of the kidneys.

When the first appearance of skin rash or any other serious adverse reaction, the drug should be discarded.

When suddenly appearing or growing cough or shortness of breath, you need to re-examine the patient and consider stopping treatment with the drug.

Excessive sunlight and ultraviolet radiation should be avoided.

The risk of side effects is much higher in patients with AIDS.

It is not recommended for use in diseases caused by beta-hemolytic streptococcus group A, due to the widespread resistance of strains.

In patients taking co-trimoxazole, cases of pancytopenia have been described. 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 senile age, hypoalbuminemia, impaired renal function, bone marrow depression. Such side reactions are more likely if methotrexate appoint in large doses. To prevent myelosuppression, it is recommended that folic acid or calcium folinate.

Trimethoprim disrupts the exchange of phenylalanine, but this does not affect patients with phenylketonuria, provided that the appropriate diet is observed.

Patients whose metabolism is characterized by "slow acetylation" are more likely to develop idiosyncrasy to sulfonamides.

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

Co-trimoxazole and, in particular, the trimethoprim included in its composition may affect the results of determination of serum mono-methotrexate concentration by competitive binding with proteins using bacterial dihydrofolate reductase as a ligand. However, in the definition of methotrexate by radioimmunity, interference does not occur.

Trimethoprim and sulfamethoxazole can affect the results of the Jaffe reaction (determination of creatinine by reaction with picric acid in alkaline medium), while in the range of normal values the results are overestimated by approximately 10%.

Effect on the ability to drive transp. cf. and fur:

Given the potential for the development of significant side effects, during the treatment period, care must be taken when driving vehicles and occupations, potentially hazardous activities requiring increased concentration and speed of psychomotor reactions.

Form release / dosage:

Suspension for oral administration 240 mg / 5 ml.

Packaging:For 80 ml of the drug in bottles of dark glass with screwed lids made of polyethylene. 1 bottle with instructions for use and a polypropylene gauge with a scale in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C. Protect from light.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N014891 / 01

Date of registration:24.06.2008 / 18.08.2010

Expiration Date:Unlimited

The owner of the registration certificate:Medan Pharma, Joint Stock CompanyMedan Pharma, Joint Stock Company Poland

Manufacturer: & nbsp

MEDANA PHARMA, S.A. Poland

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp13.02.2017

Illustrated instructions

Instructions

Biseptol® (Biseptol®)