Biseptol®
Pharmacokinetic interaction
Trimethoprim is an inhibitor of organic cation transporter 2 (OCT2), as well as a weak inhibitor of the CYP2C8 isoenzyme. Sulfamethoxazole is a weak inhibitor of the CYP2C9 isoenzyme.
Systemic exposure to drugs transported by OCT2 (eg, dofetilide, amantadine, memantine, and lamivudine) may be increased when trimethoprim-sulfamethoxazole is coadministered.
Trimethoprim-sulfamethoxazole and dofetilide should not be used simultaneously. Trimethoprim inhibits the renal excretion of dofetilide, increases the area under the concentration-time curve AUC by 103% and the maximum concentration of dofetilide by 93%. Increasing concentrations of dofetilide may cause serious ventricular arrhythmias with QT prolongation, including torsades de pointes.
Patients receiving amantadine or memantine have an increased risk of developing nervous system adverse events (such as delirium and myoclonus).
Systemic exposure to drugs predominantly metabolized by CYP2C8 (e.g., paclitaxel, amiodarone, dapsone, repaglinide, rosiglitazone and pioglitazone) may be increased when trimethoprim-sulfamethoxazole is coadministered.
Paclitaxel and amiodarone have a low therapeutic index; their simultaneous use with trimethoprim-sulfamethoxazole is not recommended.
Dapsone and trimethoprim-sulfamethoxazole may cause the development of methemoglobinemia, as there is a potential for their pharmacokinetic and pharmacodynamic interactions. Patients receiving dapsone and trimethoprim-sulfamethoxazole should be closely monitored for the development of methemoglobinemia. If necessary, alternative therapy should be prescribed. Patients receiving repaglinide or pioglitazone should be regularly monitored for the development of hypoglycemia.
Systemic exposure to drugs predominantly metabolized by the CYP2C9 isoenzyme (for example, coumarins (warfarin, acenocoumarol), phenytoin and sulfonylurea derivatives (glibenclamide, gliclazide and glipizide)) may be increased when combined with trimethoprim-sulfamethoxazole.
Blood clotting should be monitored in patients receiving coumarins. Biseptol may inhibit the hepatic metabolism of phenytoin. After administration of standard doses of trimethoprim and sulfamethoxazole, an increase in the half-life of phenytoin by 39% and a decrease in its clearance by 27% were observed. Patients receiving phenytoin should be monitored for phenytoin toxicity. Patients receiving sulfonylurea derivatives (glibenclamide, gliclazide and glipizide) should be monitored for the development of hypoglycemia.
The drug Biseptol can reduce the effectiveness of oral contraceptives. During therapy with Biseptol, women are recommended to use additional methods of contraception.
The simultaneous use of trimethoprim-sulfamethoxazole and indomethacin may cause an increase in the concentration of sulfamethoxazole in the blood plasma.
Biseptol may increase serum digoxin concentrations, especially in elderly patients, so monitoring of serum digoxin concentrations is necessary.
Pharmacodynamic interactions and interactions with unknown mechanism
The incidence and severity of myelotoxic and nephrotoxic adverse events may be increased with concomitant use of trimethoprim-sulfamethoxazole and other drugs that have a myelosuppressive effect or can cause renal impairment (nucleoside analogues, tacrolimus, azathioprine or mercaptopurine). Patients receiving such drugs concomitantly with trimethoprim-sulfamethoxazole should be monitored for the development of hematologic and/or renal toxicity.
Concomitant use with clozapine should be avoided, since the latter is known to cause agranulocytosis.
In elderly and senile patients, with the simultaneous use of certain diuretics (mainly thiazide), an increase in the number of cases of thrombocytopenia was observed.
In patients receiving diuretics, platelet levels in the blood should be regularly monitored.
Patients receiving trimethoprim-sulfamethoxazole and cyclosporine after renal transplantation may experience a reversible deterioration in renal function.
Sulfonamides, including sulfamethoxazole, may compete for protein binding and renal transport of methotrexate, thereby increasing free methotrexate concentrations and systemic effect.
Cases of pancytopenia have been described in patients taking trimethoprim and methotrexate. Trimethoprim has low affinity for human dehydrofolate reductase, but may increase the toxicity of methotrexate, especially in the presence of risk factors such as old age, hypoalbuminemia, renal impairment, bone marrow suppression, and in patients receiving high doses of methotrexate. To prevent myelosuppression, such patients should be prescribed folic acid or calcium folinate.
It can be assumed that when trimethoprim-sulfamethoxazole is co-administered to patients receiving pyrimethamine for malaria prophylaxis in doses greater than 25 mg per week, they may develop interregional anemia. Caution must be exercised during the simultaneous use of trimethoprim-sulfamethoxazole and drugs that increase the concentration of potassium in the blood serum (such as ACE inhibitors, angiotensin receptor blockers, potassium-sparing diuretics and prednisolone), due to the potassium-sparing effect of trimethoprim-sulfamethoxazole.
In addition to other drugs that may cause hyperkalemia, the combined use of trimethoprim-sulfamethoxazole (co-trimoxazole) and spironolactone may result in clinically significant hyperkalemia.
Laboratory research
Trimethoprim-sulfamethoxazole and, in particular, trimethoprim, which is part of it, may affect the results of determining the concentration of methotrexate in serum, carried out by the competitive protein binding method using bacterial dihydrofolate reductase as a ligand. However, when methotrexate is determined by the radioimmune method, there is no influence.
Trimethoprim and sulfamethoxazole can also affect the results of the Jaffe test (determination of creatinine by reaction with picric acid in an alkaline medium), and in the normal range the results are overestimated by approximately 10%.
Biseptol suspension for oral administration 240/5ml 80ml complete with measuring cup
special instructions
Co-trimoxazole should be prescribed only in cases where the advantage of such combination therapy over other antibacterial monotherapy drugs outweighs the possible risk. Because the sensitivity of bacteria to antibacterial drugs in vitro
varies across different geographic areas and over time, local patterns of bacterial susceptibility should be taken into account when selecting 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 administration of folic acid (3-6 mg/day), which does not significantly impair the antimicrobial activity of the drug. Particular caution should be exercised when treating elderly patients or patients with suspected underlying folate deficiency. The administration of folic acid is also advisable for long-term treatment in high doses. If there is a significant decrease in the number of any blood cells, the drug should be discontinued.
It is also inadvisable during treatment to consume foods containing large quantities of PABA - green parts of plants (cauliflower, spinach, legumes), carrots, tomatoes.
For long-term courses (especially in cases of renal failure), it is necessary to regularly conduct a general urine test and monitor kidney function.
To prevent crystalluria, it is recommended to maintain a sufficient volume of urine excreted. 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 skin rash or any other severe adverse reaction, the drug should be discontinued.
If cough or shortness of breath suddenly appears or worsens, the patient should be re-examined and discontinuation of drug treatment should be considered.
Excessive sunlight and ultraviolet radiation should be avoided.
The risk of side effects is significantly higher in patients with AIDS.
It is not recommended for use in diseases caused by group A beta-hemolytic streptococcus due to widespread strain resistance.
Cases of pancytopenia have been described in patients taking co-trimoxazole. Trimethoprim has low affinity for human dehydrofolate reductase, but may increase the toxicity of methotrexate, especially in the presence of other risk factors such as old age, hypoalbuminemia, renal impairment, bone marrow suppression. Such adverse reactions are more likely if methotrexate is prescribed in large doses. To prevent 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 they follow an appropriate diet.
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, trimethoprim, which is part of it, can affect the results of determining the concentration of methotrexate in serum, carried out by the competitive protein binding method using bacterial dihydrofolate reductase as a ligand. However, when methotrexate is determined by the radioimmune method, interference does not occur.
Trimethoprim and sulfamethoxazole can affect the results of the Jaffe test (determination of creatinine by reaction with picric acid in an alkaline medium), and in the normal range the results are overestimated by approximately 10%.
Biseptol Susp. for oral administration 240 mg|5 ml 80 ml №1
Pharmacokinetic interaction
Trimethoprim is an inhibitor of organic cation transporter 2 (OCT2), as well as a weak inhibitor of the CYP2C8 isoenzyme. Sulfamethoxazole is a weak inhibitor of the CYP2C9 isoenzyme.
Systemic exposure to drugs transported by OCT2 (eg, dofetilide, amantadine, memantine, and lamivudine) may be increased when trimethoprim-sulfamethoxazole is coadministered.
Trimethoprim-sulfamethoxazole and dofetilide should not be used simultaneously. Trimethoprim inhibits the renal excretion of dofetilide, increases the area under the concentration-time curve AUC by 103% and the maximum concentration of dofetilide by 93%. Increasing concentrations of dofetilide may cause serious ventricular arrhythmias with QT prolongation, including torsades de pointes.
Patients receiving amantadine or memantine have an increased risk of developing nervous system adverse events (such as delirium and myoclonus).
Systemic exposure to drugs predominantly metabolized by CYP2C8 (e.g., paclitaxel, amiodarone, dapsone, repaglinide, rosiglitazone and pioglitazone) may be increased when trimethoprim-sulfamethoxazole is coadministered.
Paclitaxel and amiodarone have a low therapeutic index; their simultaneous use with trimethoprim-sulfamethoxazole is not recommended.
Dapsone and trimethoprim-sulfamethoxazole may cause the development of methemoglobinemia, as there is a potential for their pharmacokinetic and pharmacodynamic interactions. Patients receiving dapsone and trimethoprim-sulfamethoxazole should be closely monitored for the development of methemoglobinemia. If necessary, alternative therapy should be prescribed. Patients receiving repaglinide or pioglitazone should be regularly monitored for the development of hypoglycemia.
Systemic exposure to drugs predominantly metabolized by the CYP2C9 isoenzyme (for example, coumarins (warfarin, acenocoumarol), phenytoin and sulfonylurea derivatives (glibenclamide, gliclazide and glipizide)) may be increased when combined with trimethoprim-sulfamethoxazole.
Blood clotting should be monitored in patients receiving coumarins. Biseptol may inhibit the hepatic metabolism of phenytoin. After administration of standard doses of trimethoprim and sulfamethoxazole, an increase in the half-life of phenytoin by 39% and a decrease in its clearance by 27% were observed. Patients receiving phenytoin should be monitored for phenytoin toxicity. Patients receiving sulfonylurea derivatives (glibenclamide, gliclazide and glipizide) should be monitored for the development of hypoglycemia.
The drug Biseptol can reduce the effectiveness of oral contraceptives. During therapy with Biseptol, women are recommended to use additional methods of contraception.
The simultaneous use of trimethoprim-sulfamethoxazole and indomethacin may cause an increase in the concentration of sulfamethoxazole in the blood plasma.
Biseptol may increase serum digoxin concentrations, especially in elderly patients, so monitoring of serum digoxin concentrations is necessary.
Pharmacodynamic interactions and interactions with unknown mechanism
The incidence and severity of myelotoxic and nephrotoxic adverse events may be increased with concomitant use of trimethoprim-sulfamethoxazole and other drugs that have a myelosuppressive effect or can cause renal impairment (nucleoside analogues, tacrolimus, azathioprine or mercaptopurine). Patients receiving such drugs concomitantly with trimethoprim-sulfamethoxazole should be monitored for the development of hematologic and/or renal toxicity.
Concomitant use with clozapine should be avoided, since the latter is known to cause agranulocytosis.
In elderly and senile patients, with the simultaneous use of certain diuretics (mainly thiazide), an increase in the number of cases of thrombocytopenia was observed.
In patients receiving diuretics, platelet levels in the blood should be regularly monitored.
Patients receiving trimethoprim-sulfamethoxazole and cyclosporine after renal transplantation may experience a reversible deterioration in renal function.
Sulfonamides, including sulfamethoxazole, may compete for protein binding and renal transport of methotrexate, thereby increasing free methotrexate concentrations and systemic effect.
Cases of pancytopenia have been described in patients taking trimethoprim and methotrexate. Trimethoprim has low affinity for human dehydrofolate reductase, but may increase the toxicity of methotrexate, especially in the presence of risk factors such as old age, hypoalbuminemia, renal impairment, bone marrow suppression, and in patients receiving high doses of methotrexate. To prevent myelosuppression, such patients should be prescribed folic acid or calcium folinate.
It can be assumed that when trimethoprim-sulfamethoxazole is co-administered to patients receiving pyrimethamine for malaria prophylaxis in doses greater than 25 mg per week, they may develop interregional anemia. Caution must be exercised during the simultaneous use of trimethoprim-sulfamethoxazole and drugs that increase the concentration of potassium in the blood serum (such as ACE inhibitors, angiotensin receptor blockers, potassium-sparing diuretics and prednisolone), due to the potassium-sparing effect of trimethoprim-sulfamethoxazole.
In addition to other drugs that may cause hyperkalemia, the combined use of trimethoprim-sulfamethoxazole (co-trimoxazole) and spironolactone may result in clinically significant hyperkalemia.
Laboratory research
Trimethoprim-sulfamethoxazole and, in particular, trimethoprim, which is part of it, may affect the results of determining the concentration of methotrexate in serum, carried out by the competitive protein binding method using bacterial dihydrofolate reductase as a ligand. However, when methotrexate is determined by the radioimmune method, there is no influence.
Trimethoprim and sulfamethoxazole can also affect the results of the Jaffe test (determination of creatinine by reaction with picric acid in an alkaline medium), and in the normal range the results are overestimated by approximately 10%.
