Biseptolum

General characteristics. Structure:

Active agents: sulfamethoxazole of 200 mg / 5 ml; Trimethoprimum of 40 mg / 5 ml.

Pharmacological properties:

Pharmacodynamics. Chemotherapeutic means which contains streptocide and derivative a diaminopyrimidine — Trimethoprimum in the ratio 5:1. The combination of these two drugs allowed to provide, except bacteriostatic, also bactericidal activity.
Biseptolum — drug of a broad spectrum of activity, seldom there are strains of the bacteria steady against it. Development of gram-positive microorganisms brakes in vitro: streptococci (Streptococcus pneumoniae, S. agalactiae, S. viridans), stafilokokk (Staphylococcus aureus, Staphylococcus epidermidis), Listeria monocytogenes, Nocardia asteroides and gram-negative: majority of sticks of Enterobacteriaceae (types of Salmonella, Shigella, Klebsiella, Proteus mirabilis, Enterobacter, part of strains of Escherichia coli), part of strains of H. Influenzae, Legionella spp., Yersinia enterocolitica, Brucella spp., Neisseria meningitidis, Neisseria gonorrhoeae, and also Pneumocystis carinii. It is inefficient concerning a stick of tuberculosis, viruses, the majority of anaerobic microorganisms and mushrooms.

Pharmacokinetics. After intake in a therapeutic dose quickly and almost it is completely soaked up in an upper part of a small intestine, and in 60 min. resistant effective concentration in blood and fabrics which remains for about 12 h is established. Both components are connected with proteins of a blood plasma — Trimethoprimum for 45%, and sulfamethoxazole — for 60%. Gets into fabrics and liquids of an organism: in tissue of lungs, palatine tonsils, liquor, a prostate, kidneys, liquor of an inner ear, a secret of bronchial tubes and a vagina, and also is removed with breast milk (can exert undesirable impact on newborns with insufficiency glyukozo-6-fosfatdegidrogenazy) and gets through a placental barrier. Cmax in blood is noted in 2–4 h. Biological Т½ sulfamethoxazole makes 9–11 h, Trimethoprimum — 10–12 h Т½ at children depend on age: on the first year of life — 7–8 h, 1–10 years — 5–6 h. At patients of advanced age and at renal failure Т½ increases. Out of a human body it is brought with urine: 20% of sulfamethoxazole and about 60% of Trimethoprimum are removed in not changed look, the others — in the form of metabolites.

Indications to use:

Treatment of the infections caused by microorganisms, sensitive to drug:

• respiratory infections (bronchitis, bronchial pneumonia, pneumonia, including pneumocystic);
• sinusitis, average otitis;
• infections of uric ways and kidneys (pyelonephritis, pyelitis, cystitis, urethritis, prostatitis, venereal ulcer);
• infections of bodies of a GIT (a typhoid and a paratyphoid, bacterial dysentery, cholera (in addition to recovery of liquid and electrolytes)), the diarrhea of travelers caused by enterotoksichny strains of Escherichia coli;
• other bacterial infections (treatment in a combination with other antibiotics is possible), for example a nocardiosis.

Route of administration and doses:

Drug is used orally.
Before use shake up before receiving homogeneous suspension.
5 ml of suspension contain 200 mg of sulfamethoxazole and 40 mg of Trimethoprimum.
The measure with divisions is added to a bottle.
Apply at the rate of 6 mg of Trimethoprimum and 30 mg of sulfamethoxazole on 1 kg of body weight for a while.
Usually appoint to children aged:
6 weeks-5 of month — 2,5 ml (in the morning and in the evening) with an interval of 12 h;
6 months-5 of years — 5 ml 2 times a day with an interval of 12 h;
6–12 years — 10 ml 2 times a day with an interval of 12 h.
The dosing mode for children approximately corresponds to a daily dose of 6 mg of Trimethoprimum and 30 mg of sulfamethoxazole on 1 kg of body weight.
To adults and children 12 years — 20 ml (960 mg) (in the morning and in the evening) with an interval of 12 h for 5–7 days are aged more senior. If for 7 days of treatment clinical improvement is not noticeable, it is necessary to carry out repeatedly assessment of a condition of the patient and to otkorrigirovat the scheme of treatment.
Dosing in special cases
At infection of Pneumocystis carinii of 20 mg of Trimethoprimum and 100 mg of sulfamethoxazole on 1 kg of body weight a day in equal doses each 6 h, for 14 days. The upper bound of a dose is determined by the table:

Body weight, kg	Measured spoons (doses for reception with an interval of 6 h, ml)
8	1 (5)
16	2 (10)
24	3 (15)
32	4 (20)
40	5 (25)
48	6 (30)
64	8 (40)
80

For prevention of the pneumonia caused by Pneumocystis carinii adult appoint 800 mg of sulfamethoxazole and 160 mg of Trimethoprimum. Trimethoprimum in a dose of 150 mg/sq.m/days and sulfamethoxazole — 750 mg/sq.m/days in 2 equal receptions for 3 days in a row is recommended to children.
The total daily dose should not exceed 320 mg of Trimethoprimum and 1600 mg of sulfamethoxazole. At the same time it is possible to follow the following recommendations:

Surface area of a body, sq.m	Measured spoons (doses for reception with an interval of 12 h, ml)
0,26	0,5 (2,5)
0,53	1(5)
1,06	2 (10)

At a renal or liver failure
At clearance of creatinine> 30 ml/min. — a usual dose;
at clearance of creatinine of 15-30 ml/min. — 1/2 usual doses;
at clearance of creatinine <15 ml/min. are not recommended to apply Biseptolum.

Features of use:

With extra care to apply at patients with a renal and liver failure and to patients with tendency to allergic reactions.
Treatment of patients of advanced age should not be long. At damage of kidneys the dose of drug should be otkorrigirovat according to recommendations of the section USE.
Patients of advanced age, and also patients with the available deficit of folic acid or a renal failure at treatment with Biseptolum can have hematologic changes indicating a lack of folic acid. They disappear after purpose of folic acid.
During treatment by Biseptolum in case of skin rash or other side reactions drug needs to be cancelled at once.
Patients have to use enough liquid and have an adequate diuresis for the prevention of a crystalluria.
At more long treatment it is necessary to control a blood pattern carefully. At considerable reduction of quantity of any blood cells drug should be cancelled. The patient with heavy hematologic disturbances drug is appointed only in exceptional cases.
Due to a possibility of hemolysis at patients with deficit of a glyukozo-6-phosphate-dehydrogenase drug is appointed only according to absolute indications in the minimum doses. Trimethoprimum breaks phenylalanine exchange, however it does not influence patients with a fenilketonuriya on condition of observance of the corresponding diet.
As well as at purpose of any sulfonamides, it is necessary to be the careful patient with a porphyria and dysfunction of a thyroid gland.
Use during pregnancy and feeding by a breast. Drug is not recommended to be used during pregnancy and feeding by a breast.
Children. Do not appoint to children aged to 6 weeks. Premature children cannot appoint it.
Ability to influence speed of response at control of vehicles or work with other mechanisms. It is necessary to inform the patient on need to limit control of vehicles, service of mobile mechanisms or performance of other works which demand high psychophysical activity, when developing a headache and dizziness, a disorientation, a depression, a vision disorder.

Side effects:

The recommended Biseptolum doses usually well are transferred. If side reactions arise, they are, as a rule, expressed poorly. The most frequent side effects — skin rash and gastrointestinal frustration.
Allergic reactions can develop: fervescence, Quincke's disease, anaphylactoid reactions, serum disease. In the rare occurences there can be an uzlekovy periarthritis and allergic myocarditis. Cases of fungal infections, such as candidiasis are described.
The following side effects are described (as decrease in frequency):
From a GIT: nausea (with vomiting or without), lack of appetite, stomatitis, diarrhea, is very rare — an abdominal pain, an inflammation of a mucous membrane of a stomach, isolated cases of hepatitis, a liver necrosis, separate cases of a pseudomembranous coloenteritis, increase in activity of transaminases and concentration of bilirubin. Cases of acute pancreatitis are described, however such patients had serious associated diseases including AIDS.
From system of blood: the majority of changes which revealed, were slight, asymptomatic and disappeared after drug withdrawal. Most often noted a leukopenia, thrombocytopenia and a neutropenia. In isolated cases there can be an agranulocytosis, megaloblastny, hemolitic or aplastic anemia, a methemoglobinemia, a pancytopenia or a purpura. Patients who applied Trimethoprimum combination with a methotrexate have messages on pancytopenia cases (see INTERACTIONS).
From urinary tract: in isolated cases — a renal failure, intersticial nephrite, increase in maintenance of an urea nitrogen of blood, creatinine in a blood plasma, a crystalluria. Sulfonamides, including Biseptolum, can cause increase in a diuresis, especially in patients with the hypostases caused by diseases of cardiovascular system.
From TsNS: neuropathy (including peripheral neuritis and paresthesias), hallucinations, uveitis, isolated cases of aseptic meningitis or meningeal symptomatology, ataxy, spasms, dizziness.
From a respiratory organs: separate cases of pulmonary infiltrates, similar arising at an eosinophilic or allergic alveolitis. Clinically they are shown by cough or short wind. At sudden emergence of these symptoms it is necessary to conduct examination of the patient and to consider a question of the treatment termination by Biseptolum.
From skin: side reactions are usually slight and quickly disappear after drug withdrawal. As well as for many other sulphonamide drugs, in some cases reception of Biseptolum was followed by development of a photosensitization, multiformny erythema. Very seldom chances of essential side effects from use of streptocides: Stephens's syndrome — Johnson, a Lyell's disease and Shenleyn's purpura — Genokh.
From a musculoskeletal system: seldom — arthralgias and mialgiya, separate cases of a rabdomioliz are described.
From outside metabolism: Trimethoprimum in high doses for treatment of pneumocystic pneumonia is led to oboratimy increase in level of potassium in a blood plasma. The hyperpotassemia can arise even at reception of Trimethoprimum in usual doses if at the patient potassium exchange, a renal failure is broken or at simultaneous use of the drugs provoking a hyperpotassemia. At such patients it is necessary to control potassium level in a blood plasma. Hyponatremia cases, occasionally — a hypoglycemia at patients with a renal failure, a liver disease, a hyponutrient are described or at administration of drug in high doses.
Side reactions at patients with AIDS: frequency of side reactions, especially skin rash, fever, a leukopenia and increase in activity of aminotransferases in a blood plasma at patients with AIDS is much higher, than at other patients.

Interaction with other medicines:

Biseptolum in a combination with diuretics, especially groups of tiazid, increases probability of thrombocytopenia with displays of hemorrhagic diathesis. Drug can extend a prothrombin time at those who accept anticoagulants of indirect action (for example warfarin). Brakes biotransformation in dipheninum liver (increases it Т½ to 39%). Can also increase concentration of a free methotrexate in a blood plasma (its linkng with blood proteins decreases). At patients who apply Trimethoprimum and a methotrexate pancytopenia cases were described. Trimethoprimum has insignificant affinity to human degidrofolatny reductase, but can increase toxicity of a methotrexate, especially in the presence of other risk factors — such as advanced age, hypoalbuminemia, renal failure, oppression of marrow. So, side effect of drug can be shown especially when the methotrexate is applied in high doses. It is recommended to appoint to such patients folic acid or фолинат calcium for the purpose of prevention of influence on a hemogenesis.
Strengthens effect of anti-diabetic drugs — sulphonylurea derivatives.
Phenylbutazone, salicylates and indometacin can force out streptocides from connections with proteins of a blood plasma, increasing their concentration in blood.
Barbiturates strengthen side effects of Biseptolum.
Urotropin, ascorbic acid increase risk of a crystalluria.
Biseptolum can change reaction of definition of creatinine by means of alkaline picrate by Jaffe's method (increases creatinine level approximately for 10%).
Trimethoprimum cannot be applied combined with dofetilidy. Purpose of Trimethoprimum of 160 mg and sulfamethoxazole of 800 mg 2 times a day in a combination from dofetilidy 500 mkg 2 times a day within 4 days causes increase in Cmax of a dofetilid that leads to emergence of serious ventrikulyarny arrhythmias.
At the patients accepting Biseptolum and cyclosporine after renal transplantation can note oboratimy deterioration in function of kidneys that is shown by increase in level of creatinine.
Biseptolum can reduce efficiency of tricyclic antidepressants.
Separate messages allow to assume that at co-administration by the patient Biseptola for prevention of malaria in doses over 25 mg/week, at them can develop megaloblastny anemia.
One case of a toxic delirium after a concomitant use of Biseptolum and an amantadin is described.
Biseptolum, namely Trimethoprimum which is its part can affect results of definition of concentration of the methotrexate in a blood plasma which is carried out by method of competitive linkng with proteins using a bacterial digidrofolatreduktaza as a ligand. However when determining a methotrexate by a radio immune method of an interference does not arise.

Contraindications:

Hypersensitivity to streptocides, Trimethoprimum and other components of drug; period of pregnancy and feeding by a breast; insufficiency glyukozo-6-fosfatdegidrogenazy; serious illness of a liver and kidneys (clearance of creatinine <15 ml/min.).
Not to appoint drug at an agranulocytosis, a leukopenia, megaloblastny anemia, a hyperbilirubinemia at children.
Not to appoint to premature, newborn children of chest age to 6 weeks.
It is not recommended to apply at streptococcal quinsy.
It is impossible to appoint in a combination with dofetilidy.
Not to appoint to patients to whom the chemotherapy is carried out.

Overdose:

Acute poisoning — nausea, vomiting, gripes, diarrhea, a headache and dizziness, drowsiness, a loss of consciousness, high temperature of a body, a vision disorder, a depression, a disorientation, a hamaturia and a crystalluria. Disturbances of indicators of a gemogramma and jaundice are late symptoms of overdose. In this case appoint specific treatment. For elimination of action of Trimethoprimum it is possible to appoint to a hemopoiesis фолинат calcium in a dose 3–6 mg for 5–7 days.
Chronic intoxication — use of limit doses and/or long treatment can be the cause of oppression of function of marrow which is shown by thrombocytopenia, a leukopenia, megaloblastny anemia. Other pathological changes of a picture of blood — a consequence of insufficiency of folic acid.
Treatment (depending on symptomatology): to stop drug use, to cause vomiting, to wash out a stomach; strengthening of renal excretion by an artificial diuresis (alkalization of urine promotes sulfamethoxazole removal), a hemodialysis (peritoneal dialysis is inefficient). It is necessary to control a pattern of blood and indicators of electrolytes. At the expressed pathological changes of a picture of blood or jaundice appoint nonspecific treatment. For elimination of action of Trimethoprimum it is possible to appoint to a hemopoiesis фолинат calcium in a dose 3–6 mg for 5–7 days.

Storage conditions:

To store in original packaging at a temperature not above 25 °C. After opening of a bottle to store with densely closed cover within 8 months.

Issue conditions:

According to the recipe

Packaging:

Susp. for перорал. comment of 240 mg / 5 ml фл. 80 ml, No. 1.