Biseptrim

General characteristics. Structure:

Active agents: sulfamethoxazole of 400 mg, Trimethoprimum of 80 mg.

Excipients: potato starch, sodium of starch glikolit, silicon dioxide colloid (aerosil), calcium stearate.

Pharmacological properties:

Pharmacokinetics. Both components of drug are quickly soaked up from a digestive tract; their maximum concentration in blood serum is reached in 1-4 hours after intake.

Trimethoprimum contacts proteins of serum approximately for 50%, sulfamethoxazole - for 66%. Distribution of both connections differs: streptocide is distributed only in an extracellular kompartment, Trimethoprimum - in all fluid mediums of an organism. High concentration of Trimethoprimum is observed, including, in a secret of bronchial glands, prostates and in bile. Concentration of sulfamethoxazole in biological liquids are lower. Both connections collect in effective concentration in a phlegm, vulval allocations and a secret of a middle ear. Active components of drug get into breast milk and through a placental barrier. Both substances are metabolized in a liver: streptocide - by acetylation and linkng with glucuronic acid, Trimethoprimum - by oxidation and a hydroxylation. Components of drug are brought out of an organism generally through kidneys, as by filtering, and active canalicular secretion. Concentration of active connections in urine are much higher, than in blood. Within 72 hours with urine 84,5% of the accepted dose of streptocide and 66,8% of Trimethoprimum are removed. The elimination half-life of Trimethoprimum makes 8,6-17 hours, sulfamethoxazole - 9-11 h.

Pharmacodynamics. Biseptrim - an antimicrobic microbicide of a broad spectrum of activity. The combined drug contains co-trimoxazole - mix of Trimethoprimum and sulfamethoxazole (1:5). The effect is connected with the double blocking effect of drug on metabolism of bacteria. Sulfamethoxazole breaks synthesis of dihydrofolic acid in bacterial cells, and Trimethoprimum interferes with transformation of dihydrofolic acid into tetrahydrofolic. High concentration of drug is created in tissues of lungs, kidneys, a prostate, in cerebrospinal fluid, bile, bones. Biseptrim is active concerning gram-positive bacteria: streptococci (Streptococcus pneumoniae, S. agalactiae, S. viridans), stafilokokk (Staphylococcus aureus, Staphylococcus epidermidis), Branhamella catarrhalis, Listeria monocytogenes, Nocardia asteroides and gram-negative, including 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, Cyclospora cayetanensis, Cirobacter, Hafnia alvei, Serratia, Morganella morganii, Vibrio cholera, Edwardsiella tarda, Alcaligenes faecalis, Pseudomonas cepacia, Burkholderia (Pseudomonas) pseudomallei, Haemopilus ducreyi, Providentia, Stenotrophomonas maltophilia, Acinetobacter lwoffi, Acinetobacter anitratus, Aeromonas hydrophilia.

Mycobacteriaceae sticks, viruses, the majority of anaerobic bacteria and mushrooms are steady against drug.

Indications to use:

- infections of upper and lower urinary tract (urethritis, cystitis, pyelitis, pyelonephritis);

- infections of upper and lower respiratory tracts (bronchitis acute and chronic, a bronchoectatic disease, the pneumonia including caused by Pneumocystis carinii);

- infections of ENT organs (acute average otitis, sinusitis);

- digestive tract infections (typhoid, paratyphoid, salmonellonositelstvo, cholera, dysentery);

- infections of skin and soft tissues (pyoderma, abscess, wound fever);

- osteomyelitis acute and chronic;

- a brucellosis, a nocardiosis, an actinomycosis, a toxoplasmosis, the South American zymonematosis (the combination to other antibiotics is possible).

Route of administration and doses:

Drug is used inside, after meal, with enough liquid. Drug should be used strictly on doctor's orders.

Children are from 6 to 12 years old: 240-480 mg 2 times a day every 12 hours, the daily dose makes 48 mg/kg of body weight. Adults and children are more senior than 12 years: 960 mg (2 tablets on 480 mg) 2 times a day every 12 hours. The daily dose should not exceed 1920 mg (4 tablets on 480 mg).

The course of treatment makes 7-10 days. In the absence of positive clinical effect in 7 days of therapy, it is necessary to reconsider treatment of the patient.

At persistent infections a course of treatment longer also depends on disease severity.

Dosing in special cases. Patients with clearance of creatinine of 15-30 ml/min. should reduce a dose twice. At clearance of creatinine less than 15 ml/min. Biseptrim's use is not recommended.

Patients of advanced age. Drug should be accepted carefully to patients of advanced age owing to increase in risk of side effects, especially at patients with a renal/liver failure or accepting at the same time other medicines.

In the absence of special instructions it is necessary to accept standard doses of drug.

Features of use:

Biseptrim it is necessary to appoint only when, according to the doctor, advantages of such therapy exceed possible risk. It is necessary to decide whether it is possible to manage use of one effective antibacterial agent.

Patients of advanced age, and also at associated diseases of a liver and kidneys or a concomitant use of other drugs have higher risk of development of heavy allergic reactions, such as an exudative multiformny erythema (Stephens-Johnson's syndrome), a toxic epidermal necrolysis (Lyell's disease) and a fulminant necrosis of a liver. For reduction of risk of similar reactions treatment by Biseptrim has to be as much as possible short-term, especially at elderly.

At damage of kidneys the dose should be corrected as directed the section "Dosing in Special Cases".

At the first emergence of skin rash or any other heavy side reaction drug needs to be cancelled.

At sudden emergence or increase of cough or asthma it is necessary to inspect repeatedly the patient and to consider a question of the termination of treatment by Biseptrim.

Biseptrim it is necessary to appoint with care the patient with tendency to allergic reactions, with bronchial asthma, dysfunction of a thyroid gland, a serious illness of cardiovascular system. In these cases the dose of drug needs to be reduced, and to increase intervals between receptions.

At therapy course duration more than 5 days and/or increase in a dose of drug it is necessary to control a pattern of peripheral blood; at emergence of pathological changes it is necessary to appoint folic acid in a dose of 5-10 mg/days or фолинат calcium. At considerable decrease in number of any blood cells Biseptrim is recommended to cancel.

Patients of advanced age, and also with deficit of folic acid or a renal failure can have hematologic changes characteristic of a lack of folic acid.

The patient, it is long receiving Biseptrim (especially at a renal failure), regular control of the general analysis of urine and function of kidneys is necessary. During treatment it is necessary to provide sufficient intake of liquid in an organism, an adequate diuresis for prevention of a crystalluria.

Trimethoprimum breaks phenylalanine exchange, however it does not influence a condition of patients with a fenilketonuriya on condition of observance of the corresponding diet.

It is inexpedient to use against the background of treatment the foodstuff containing in large numbers of PABK (para-aminobenzoic acid) - green parts of plants (a cauliflower, spinach, bean), carrots, tomatoes.

During treatment it is necessary to avoid direct solar and UF-radiations, in connection with risk of development of a photosensitization.

At patients with AIDS who apply Biseptrim in connection with a pneumocystic infection such symptoms as rash, fever, a leukopenia, increase in activity of aminotransferases, a hyperpotassemia and a hyponatremia develop more often.

It is not recommended to use drug at the diseases caused by a beta and hemolitic streptococcus of group A because of eurysynusic resistance of strains.

Because of a possibility of hemolysis by the patient with deficit of a glyukozo-6-phosphate-dehydrogenase Biseptrim appoint only according to absolute indications and in the minimum doses.

At the patients accepting Biseptrim in high doses it is regularly necessary to control potassium level in blood serum.

The high doses of drug which are used at treatment of pneumocystic pneumonia can bring to progressing, but to reversible increase in content of potassium in serum at considerable number of patients. Even reception of the recommended drug doses can cause a hyperpotassemia if it is appointed against the background of disturbances of potassium exchange, a renal failure or a concomitant use of the drugs provoking a hyperpotassemia.

At treatment by high doses of Biseptrim it is necessary to consider a possibility of development of a hypoglycemia, usually in several days after an initiation of treatment. The risk of a hypoglycemia is higher at patients with renal failures, liver diseases, insufficiently adequate diet of food.

Patients whose metabolism is characterized by slow acetylation are more inclined to development of an idiosyncrasy to streptocides.

Considering a possibility of side effects of drug, it is necessary to be careful when driving or potentially dangerous mechanisms.

Side effects:

Often (> 0,01):

- lack of appetite, nausea, vomiting, diarrhea;

- a skin itch, rash (are expressed poorly and quickly disappear after drug withdrawal ).

Seldom (> 0,0001):

- a leukopenia, a neutropenia, thrombocytopenia (are most often expressed poorly or proceed asymptomatically and disappear after drug withdrawal);

- agranulocytosis, pancytopenia, megaloblastichesky, hemolitic or aplastic anemia, methemoglobinemia;

- stomatitis, a glossitis, emergence of dysbacteriosis and risk of developing of a candidosis infection, pseudomembranous colitis is possible;

- headache, dizziness, sonitus.

Very seldom (<0,0001):

- pseudomembranous coloenteritis;

- fungal infections, such as candidiasis;

- hypersensitivity reactions (fervescence, a Quincke's disease, anaphylactoid reactions, such as a serum disease, pulmonary infiltrates as an eosinophilic or allergic alveolitis with cough or short wind);

- progressing, but a reversible hyperpotassemia, a hyponatremia, especially at advanced age;

- hyperglycemia;

- hallucinations;

- neuropathy (including, peripheral neuritis and paresthesias), uveitis;

- increase in activity of transaminases and concentration of bilirubin in blood serum, hepatitis, a cholestasia, a liver necrosis;

- photosensitization;

- a renal failure (increase in an urea nitrogen, creatinine in blood serum, intersticial nephrite, a crystalluria);

- arthralgias, mialgiya.

Isolated cases of a nodular periarteritis, allergic myocarditis, aseptic meningitis or meningeal symptomatology, ataxy, spasms, dizzinesses, acute pancreatitis are described, however such patients had serious associated diseases, including AIDS, a syndrome of "a disappearing bilious channel", a multiformny erythema, Stephens-Johnson's syndrome, a toxic epidermal necrolysis (Lyell's disease), a hemorrhagic vasculitis, rabdomiolizy.

Interaction with other medicines:

At Biseptrim's appointment patients who already receive anticoagulants should remember possible strengthening of anticoagulative effect. In such cases it is necessary to define a blood clotting time repeatedly. Drug extends half-life of Phenytoinum and, thereby, increases its anticonvulsant activity. At co-administration of drugs careful monitoring of a condition of the patient and concentration of Phenytoinum in blood serum is necessary.

At the patients receiving Biseptrim and cyclosporine after transplantation of a kidney the reversible deterioration in function of kidneys which is shown increase in level of creatinine in blood serum can be observed.

Increase in serumal concentration of digoxin, especially at elderly patients is possible, at a concomitant use with Biseptrim.

Drug can reduce efficiency of tricyclic antidepressants.

At the patients accepting Biseptrim and a methotrexate pancytopenia cases are described. Trimethoprimum which is Biseptrim's part has low affinity to a degidrofolatreduktaza of the person, however can increase toxicity of a methotrexate, especially in the presence of other risk factors, such as advanced age, a hypoalbuminemia, a renal failure, oppression of marrow. These side reactions are more probable if the methotrexate is appointed in high doses. Therefore at a concomitant use with Biseptrim it is necessary to lower a methotrexate dose in order to avoid strengthening of its toxic effects.

At a concomitant use with APF inhibitors the risk of development of a heavy hyperpotassemia increases.

At co-administration of Biseptrim by the patient which receive Pyrimethaminum for prevention of malaria in doses more than 25 mg a week megaloblastichesky anemia can develop.

As well as other streptocides, Biseptrim can exponentiate effect of peroral glucose-lowering drugs from group of sulphonylurea.

Joint reception of diuretics (is more often tiazidovy and at elderly patients) increases risk of development of thrombocytopenia.

At simultaneous use with NPVP increase in concentration of sulfamethoxazole in blood is possible.

Simultaneous use of Biseptrim and rifampicin can lead to increase in concentration of rifampicin in blood serum and to delay of half-life of Trimethoprimum.

The concomitant use of antiviral drugs (zidovudine) can increase risk of development of hematologic side reactions of Biseptrim.

Trimethoprimum, inhibiting transport system of kidneys, increases AUC by 103% and Cmax for 93% of a dofetilid that increases risk of development of ventricular arrhythmias with lengthening of an interval of QT, including arrhythmia like "pirouette". Simultaneous use of a dofetilid and Trimethoprimum is contraindicated.

Laboratory researches. Biseptrim can affect results of definition of concentration of a methotrexate in serum by method of competitive linkng with proteins when as a ligand the bacterial digidrofolatreduktaza is applied. When determining a methotrexate by a radio immune method of distortions does not arise.

Results of reaction of Jaffe - definition of creatinine on reaction with picric acid in the alkaline environment - can be overestimated approximately by 10% at the patients accepting Biseptrim.

Contraindications:

- hypersensitivity to streptocides, Trimethoprimum and/or other components of drug;

- heavy liver failure;

- heavy renal failure;

- serious illness of system of a hemopoiesis (aplastic anemia, B12-scarce anemia, leukopenia, agranulocytosis), porphyria;

- treatment of the tonsillitis caused by a β-hemolitic streptococcus;

- a concomitant use with dofetilidy;

- children's age up to 6 years;

- pregnancy and period of a lactation.

Overdose:

Symptoms: nausea, vomiting, dizziness, a headache, drowsiness, an ataxy, the general weakness, puffiness of the person, frustration of an urination, oppression of a hemopoiesis (pancytopenia) - at long administration of drug.

Treatment: a gastric lavage, reception of the adsorbed coal, a large amount of liquid for maintenance of a diuresis, correction of electrolytic disturbances. At emergence of symptoms of oppression of marrow appoint the corresponding therapy.

Storage conditions:

To store in the dry, protected from light place at a temperature not above 30 °C. 

 

To store in the place, unavailable to children!

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging from a film of polyvinyl chloride and aluminum foil.

On 2 planimetric packagings together with the approved instruction on a medical use in the state and Russian languages put in a pack from a cardboard.