Biseptol 480 - instructions for use, dose, side effects, contraindications

Excipients: propylene glycol 400.00 mg, ethyl alcohol 96% 100.00 mg, alcohol gasoline 15.00 mg, sodium disulfite (E223) 1.00 mg, sodium hydroxide 12.63 mg, sodium hydroxide 10% solution to pH 9.5 - 11.0, water for injection up to 1 ml.

In 1 ampoule (5 ml) contains 400 mg of sulfamethoxazole and 80 mg of trimethoprim.

Description:Transparent colorless or slightly yellowish liquid.

Pharmacotherapeutic group:Antimicrobial agent combined.

ATX: & nbsp

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

Pharmacodynamics:

Biseptol is a combined antibacterial agent containing co-trimoxazole - a mixture in a 5: 1 ratio of sulfamethoxazole and trimethoprim. Sulfamethoxazole inhibits the synthesis of folic acid by competitive antagonism with para-aminobenzoic acid, i.e. has a bacteriostatic effect.

Trimethoprim is an inhibitor of bacterial dihydrofolate reductase. Depending on the conditions, it can exert bactericidal or bacteriostatic action. Thus, trimethoprim and sulfamethoxazole block two consecutive stages of purine biosynthesis, and then the nucleic acids required for numerous bacteria.

Biseptol is a broad-spectrum bactericidal drug that is active against the following microorganisms: Streptococcus spp. (Streptococcus pneumoniae), Staphylococcus spp., Neisseria meningitidis, Neisseria gonorrhoeae, Escherichia coli (including enterotoxogenic strains). Salmonella spp. (including Salmonella typhi and Salmonella paratyphi), Vibrio cholerae, Bacillus anthracis, Haemophilus influenzae (including ampicillin-resistant strains), Listeria spp., Nocardia asteroides, Bordetella pertussis, Enterococcus faecalis, Klebsiella spp., Proteus spp., Pasteurella spp., Francisella tularensis. Brucella spp., Mycobacterium spp. (incl. Mycobacterium leprae), Citrobacter, Enterobacter spp., Legionella pneumophila, Providencia, some species Pseudomonas (Besides Pseudomonas aeruginosa), Serratia marcescens, Shigella spp., Yersinia spp., Morganella spp., Pneumocystis carinii; Chlamydia spp. (incl. Chlamydia trachomatis, Chlamydia psittaci); protozoa: Plasmodium spp., Toxoplasma gondii, pathogenic fungi: Actinomyces israelii, Coccidioides immitis, Histoplasma capsulatum, Leishmania spp.

Resistant to the drug: Corynebacterium spp., Pseudomonas aeruginosa, Mycobacterium tuberculosis. Treponema spp., Leptospira spp., viruses.

Pharmacokinetics:The maximum concentration of sulfamethoxazole and trimethoprim, determined after one hour, is higher and is achieved more quickly with intravenous administration, compared with the concentration obtained when taking the drug inside. Significant differences in plasma concentration, half-life and elimination after administration of co-trimoxazole in oral and intravenous form have not been established. Trimethoprim is a weak alkali (pKa = 7.3) with lipophilic properties. The concentration of trimethoprim in tissues is higher than the concentration determined in plasma, especially high in the lungs and kidneys. Higher concentrations of trimethoprim in comparison with plasma are observed in bile, fluid and tissues of the prostate gland, sputum, vaginal discharge.Concentrations of trimethoprim in breast milk, cerebrospinal fluid, the secretion of the middle ear, synovial fluid, intracellular fluid (interstitial) correspond to the concentrations necessary for antibacterial action. Trimethoprim penetrates the amniotic fluid and fetal tissues, reaching a concentration there close to the concentration observed in the mother's blood serum.

Approximately 50% of trimethoprim binds to plasma proteins. The half-life in persons with normal renal function is 8.6 to 17 hours. There were no significant differences in the elderly compared with young patients.

Trimethoprim is excreted mainly by the kidneys - approximately 50% unchanged for 24 hours with urine. Several metabolites of trimethoprim have been identified in the urine.

Sulfamethoxazole is a weak acid with pKa = 6.0. The concentration of the active form of sulfamethoxazole in the amniotic fluid, bile, cerebrospinal fluid, the secretion of the middle ear, sputum, synovial fluid, intracellular of the liquid is 20 to 50% of the sulfamethoxazole present in the plasma.

Approximately 66% of sulfamethoxazole binds to plasma proteins. Period

elimination half-life in individuals with normal renal function is 9 to 11 hours. In subjects with impaired renal function values change in half-life of the active form of sulfamethoxazole not set, but the elongation is observed half-life of the main acetylated metabolite if the creatinine clearance less than 25 mL / min.

Sulfamethoxazole is excreted primarily by the kidneys, from 15 to 30% of the administered dose is found in the urine in the active form. In elderly patients, there is a decrease in renal clearance of sulfamethoxazole.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to co-trimoxazole:

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

- infections of the respiratory tract: chronic bronchitis, treatment and prevention of pneumonia caused by Pneumocystis jiroveci (formerly R. carinii) (PSR);

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

- infection FCT: typhoid fever and paratyphoid, cholera, dysentery, gastroenteritis caused by enterotoxic strains Escherichia coli;

- other bacterial infections: nocardiosis, brucellosis, actinomycosis, South American blastomycosis, toxoplasmosis.

Biseptol 480 should be used in cases when oral administration of the drug is impossible (or not recommended), or, according to the doctor, it is necessary to use a drug containing two antibacterial ingredients.

Contraindications:

- Hypersensitivity to sulfonamides, trimethoprim, co-trimoxazole or any auxiliary component of the drug;

- severe damage to the liver parenchyma;

- severe renal failure (CC less than 15 ml / min);

- liver failure;

- severe hematologic disorders: aplastic anemia, B 12-deficiency anemia, agranulocytosis, leukopenia, deficiency of glucose-6-phosphate dehydrogenase;

- should avoid the introduction of the drug with diagnosed porphyria or patients who have a risk of developing acute porphyria, t. the drug may increase the symptoms of this disease;

- children under 3 years of age (with the exception of treatment or prevention of pneumonia caused by Pneumocystis jiroveci);

- pregnancy and lactation.

Carefully:Caution should be exercised in prescribing Biseptolum to 480 patients with folic acid deficiency (eg, people with Alcohol Dependence,

treatment with anticonvulsants, with malabsorption syndrome and the elderly); patients with bronchial asthma and severe allergy; patients with diseases of the circulatory system and respiratory system; After the introduction of high doses, excessive hydration may occur; patients with thyroid disease. It is recommended that special care is taken in elderly patients, since this group is more susceptible to side effects and more likely to experience significant side effects, especially with concomitant diseases, for example, kidney failure and / or violations of liver function and other medications.

Pregnancy and lactation:

Do not prescribe the drug during pregnancy and during breastfeeding.

Dosing and Administration:Intravenously drip.

Biseptol 480, concentrate for solution for infusion, intended

only for intravenous administration, and it should be diluted immediately before use.After the administration of Biseptol 480 in the infusion solution, the resulting mixture must be vigorously shaken for the purpose of complete mixing. In the event of a precipitate or the appearance of crystals before mixing or during infusion, the mixture should be destroyed and a new one prepared.

Recommended the following scheme of breeding Biseptol 480:
1 ampoule (5 ml) of Biseptol 480 in 125 ml of solution for infusion;

2 ampoules (10 ml) of Biseptol 480 in 250 ml of solution for infusion;

3 ampoules (15 ml) of Biseptol 480 in 500 ml of the infusion solution.
The following solutions for infusion to dilute Biseptol 480:

- 5% and 10% dextrose solution;

- 0.9% solution of sodium chloride;

- Ringer's solution;

- 0.45% solution of sodium chloride with 2.5% dextrose solution.

The prepared infusion solution for Biseptol 480 should not be mixed with other drugs or other infusion solutions.

The duration of the infusion should be approximately 60 - 90 minutes and depends on the degree of hydration of the patient. If a patient is contraindicated in administering a large amount of fluid, a higher concentration of co-trimoxazole, 5 ml in 75 ml of 5% dextrose, is allowed. Unused solution should be poured.

Acute infections

Adults and children over the age of 12: usually apply 2 ampoules (10 ml) every 12 hours.

Children between the ages of 3 and 12: at the rate of 30 mg sulfamethoxazole and 6 mg trimethoprim per kg body weight per day, in 2 injections.

Dosage regimen of the preparation Biseptol 480 (before administration, the drug should be diluted as described above):

- children aged 3 to 5 years: 2.5 ml every 12 hours.

- children aged 6 to 12 years: 5 ml every 12 hours.

In the case of very serious infections in all age groups, doses can be increased by 50%.

Treatment should be performed for at least five days or two days after the symptoms disappear.

Patients with renal insufficiency: in the case of adults and children over 12 years of age (data on children under the age of 12 years are absent) with renal failure, the dosage of the drug should be modified depending on the creatinine clearance.

Clearance creatinine (ml / min)	Recommended dosing
Above 30 ml / min	Usual Dose
From 15 to 30 ml / min	1/2 of the usual dose
Less than 15 ml / min	Application is not recommended

It is recommended to determine the serum sulfamethoxazole concentration every 2-3 days in samples taken 12 hours after the administration of Biseptol 480.

If the total concentration sulfamethoxazole exceeds 150 μg / ml, treatment should be discontinued until the concentration drops below 120 μg / ml.

Pneumonia caused by Pneumocystis jiroveci (formerly R. carinii)

Treatment

At the rate of 100 mg of sulfamethoxazole and 20 mg of trimethoprim per kg of body weight per day in 2 or more divided doses. At the first opportunity, the patient should switch to the oral form of the drug. The course of treatment should not exceed 14 days. The aim of the therapy is to achieve a maximum concentration of trimethoprim in the plasma, greater than or equal to 5 μg / ml (determined in patients receiving the drug intravenously drip for an hour).

Prevention

Usual dosing (intravenously or orally (in the appropriate dosage form), if possible) during the entire exposure time. Toxoplasmosis

For prophylaxis, the same dosing is assumed as for the prevention of PCP (pneumonia caused by Pneumocystis jiroveci).

Side effects:

From the central nervous system: headache, apathy, tremor, aseptic meningitis, convulsions, neuritis, ataxia, dizziness, tinnitus, depression, hallucinations.

From the respiratory system: bronchospasm, cough, shallow breathing, pulmonary infiltrates.

From the digestive system: gastritis, abdominal pain, cholestasis, nausea, vomiting, diarrhea, stomatitis, pseudomembranous colitis, cholestatic hepatitis, increased activity of "liver" transaminases, hyperbilirubinemia, liver necrosis, glossitis, pancreatitis.

From the hematopoiesis: leukopenia, neutropenia, thrombocytopenia, hypoprothrombinemia, agranulocytosis, interregional anemia, aplastic anemia, hemolytic anemia, methemoglobinemia, eosinophilia, purpura, hemolysis in hypersensitive patients with deficiency of glucose-6-phosphate dehydrogenase.

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

From the musculoskeletal system: arthralgia, myalgia.

From the immune system: Serum sickness, anaphylactic reactions, allergic myocarditis, vasomotor rhinitis, drug fever,hemorrhagic vasculitis (Shenlaine-Genocha), nodular periarteritis, systemic lupus erythematosus.

From the skin and subcutaneous tissue: skin rash, photosensitivity, exfoliative dermatitis, persistent drug-induced rash, polymorphic erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), Quincke's edema, reddening of the sclera.

Disturbance of metabolism and alimentation: hyperkalemia, hypoglycemia, hyponatremia, anorexia.

Infections and parasitic diseases: candidiasis.

Local reactions: thrombophlebitis, tenderness at the injection site.

Overdose:

Symptoms: nausea, vomiting, dizziness, headache, confusion. With a severe form of an overdose of trimethoprim, bone marrow depression was noted.

Treatment: In case of side effects, immediately discontinue the drug. Introduction of liquid, correction of electrolyte disturbances. If necessary, hemodialysis.

Interaction:

Co-trimoxazole is compatible with the following preparations: 5% dextrose for intravenous infusions, 0.9% sodium chloride for intravenous infusions, a mixture of 0.18% sodium chloride and 4% dextrose for intravenous infusions, 6% dextran 70 for IV infusions in 5% dextrose or in physiological saline, 10 % dextran 40 for intravenous infusions at 5 % dextrose or saline solution, Ringer's solution for injection.

In elderly patients, biseptol in combination with diuretics, in particular thiazide diuretics, increases the risk of thrombocytopenia. Simultaneous use with cyclosporine reduces its concentration in the blood.

Do not administer the drug intravenously in combination with drugs and solutions containing bicarbonates.

Increases the anticoagulant activity of indirect anticoagulants, enhances the effect of hypoglycemic agents and methotrexate. Reduces the intensity of hepatic metabolism of phenytoin (prolongs its T1 / 2 by 39%) and warfarin, enhancing their effect.When co-trimoxazole and rifampicin are used concomitantly, the half-life of trimethoprim is reduced within a week.

Patients taking prophylactic pyrimethamine (antimalarial drug) in doses exceeding 25 mg / week, in the treatment with co-trimoxazole, cases of megaloblastic anemia development have been noted. It is not recommended to use combination therapy of this type.

With the simultaneous use of co-trimoxazole and zidovudine, the risk of developing hematologic disorders increases, and blood tests should therefore be performed.Increases serum concentrations of digoxin, especially in elderly patients (the control of digoxin concentrations in serum is necessary).

Reduce the therapeutic effect of co-trimoxazole benzocaine, procaine, procainamide and other medicines, as a result of the hydrolysis of which PABC is formed.

Between diuretics (thiazides, furosemide and others) and oral hypoglycemic drugs (sulfonylureas derivatives) on the one hand and antimicrobial sulfonamides on the other - it is possible to develop a cross-allergic reaction. Phenytoin, barbiturates, PASC increase manifestations of folic acid deficiency.

In patients taking cyclosporins (for example, after kidney transplantation) in the treatment with co-trimoxazole, transient impairment of renal function was observed.

With the simultaneous use of co-trimoxazole and procainamide or amantadine, an increase in the serum concentration of the listed drugs may occur.

The derivatives of salicylic acid enhance the action of co-trimoxazole.

Ascorbic acid, hexamethylenetetramine and other drugs, acidifying urine, increase the risk of developing crystalluria.

Co-trimoxazole reduces the reliability of oral contraception (inhibits the intestinal microflora and reduces the intestinal hepatic circulation of hormonal compounds).

Special instructions:

During the use of the drug should maintain proper diuresis. In depleted patients, the risk of sulfonamide crystals is increased.

In the case of long-term administration of the drug, regular laboratory blood tests are recommended, since there is a possibility of hematological changes associated with a deficiency of folic acid.

After using the drug, diarrhea may appear, which may be a symptom of pseudomembranous colitis. It is necessary to stop the use of the drug and to cancel the anti-diarrheal remedies.

Do not use Biseptol 480 in the treatment of pharyngitis caused by group A beta-hemolytic streptococci.

Caution should be exercised in patients using other medications that can cause hyperkalemia, including potassium-sparing diuretics.

It is recommended to monitor the potassium concentration in the serum, given the risk of increasing its concentration (hyperkalemia).

In case of the appearance of the first symptoms of skin rash, stop using the drug.

Given the content of benzyl alcohol in the preparation Biseptol 480 (15 mg benzyl alcohol in 1 ml solution), the drug should not be used in preterm and infants. Benzyl alcohol can cause intoxication and anaphylactoid reactions in infants and children up to 3 years of age.

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

During the treatment period, care must be taken when driving vehicles and engaging in potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Concentrate for the preparation of a solution for infusions (80.00 mg + 16.00 mg) / ml.

Packaging:5 ml per ampoule of colorless hydrolytic glass (class 1, Hebrew Pharm.). Above the place of incision of the ampule is a point of white or red color, and also a strip in the form of a ringlet of yellow color. 5 ampoules are placed in a tray for ampoules made of PVC. Two pallets in a cardboard box with instructions for use.

Storage conditions:Keep in a dark place at temperature not higher than 25 ° С.

Do not freeze!

Keep out of the reach of children.

Shelf life:5 years.

Not apply the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N 015943/01

Date of registration:12.04.2010 / 11.09.2012

Expiration Date:Unlimited

The owner of the registration certificate:Warsaw Pharmaceutical Plant Polfa, JSCWarsaw Pharmaceutical Plant Polfa, JSC Poland

Manufacturer: & nbsp

Warsaw Pharmaceutical Factory Polfa A.O. Poland

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp13.02.2017

Illustrated instructions

Instructions

Biseptol® 480 (Biseptol® 480)