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%.
Biseptol® 480 (Biseptol® 480)
Hypersensitivity and allergic reactions: at the first appearance of skin rash or any other severe adverse reaction, the drug should be discontinued. Patients with a tendency to allergic reactions and bronchial asthma should be prescribed co-trimoxazole with caution.
Infiltrates in the lungs (like eosinophilic and allergic alveolitis) can manifest themselves with symptoms such as cough or shortness of breath. If these symptoms appear or suddenly increase, it is necessary to re-examine the patient and consider stopping treatment with co-trimoxazole.
Renal disorders: Sulfonamides, including co-trimoxazole, may increase diuresis, especially in patients with edema due to heart failure. Careful monitoring of renal function and serum potassium concentrations is necessary in patients receiving high doses of co-trimoxazole (including in the treatment of pneumonia caused by P. jirovecii), as well as in the following groups of patients: patients with a history of impaired potassium metabolism receiving standard doses drug; patients with renal failure; patients receiving drugs that contribute to the development of hyperkalemia.
Serious Adverse Reactions: Fatalities, although rare, have been reported associated with adverse reactions such as blood abnormalities, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), drug reaction with eosinophilia and systemic manifestations (DRESS syndrome), and fulminant liver necrosis.
Special groups of patients: in elderly and senile patients, as well as in patients with concomitant diseases, for example, impaired renal and/or liver function, or while taking other drugs, there is an increased risk of severe adverse reactions; in these cases, the risk is related to the dose and duration of therapy. Patients should be informed of the signs and symptoms of these serious side effects and closely monitored for skin reactions.
The risk of severe skin reactions is greatest in the first few weeks of treatment. If signs or symptoms of severe skin reactions occur (eg, progressive rash, often with blisters or associated mucosal lesions), cotrimoxazole therapy should be discontinued. The course of these reactions is largely determined by early diagnosis and immediate cessation of all suspected medications, which improves the prognosis. Following the occurrence of severe skin reactions associated with the use of co-trimoxazole, the patient should never re-use co-trimoxazole.
The duration of treatment with co-trimoxazole should be as short as possible, especially in elderly and senile patients.
If renal function is impaired, the dose should be adjusted. Patients with severe renal impairment (creatinine clearance 15-30 ml/min) receiving co-trimoxazole should be carefully monitored for the development of symptoms of toxicity (nausea, vomiting, hyperkalemia).
In elderly and senile patients, as well as in patients with pre-existing folic acid deficiency or renal failure, hematological changes characteristic of folic acid deficiency may occur. They disappear after administration of folic acid.
Due to the possibility of hemolysis, co-trimoxazole should not be prescribed to patients with glucose-6-phosphate dehydrogenase deficiency.
As with any sulfonamides, caution must be exercised in patients with thyroid dysfunction.
Patients whose metabolism is characterized by “slow acetylation” are more likely to develop idiosyncrasy to sulfonamides.
Long-term therapy: with long-term administration of co-trimoxazole, it is necessary to regularly determine the number of blood cells.
If there is a significant decrease in the number of any blood cells, co-trimoxazole should be discontinued.
Patients receiving long-term treatment with co-trimoxazole (especially with renal failure) should regularly undergo a general urine test and monitor kidney function. During treatment, it is necessary to ensure sufficient fluid intake and adequate diuresis to prevent crystalluria.
Pseudomembranous colitis caused by Clostridium difficile can appear both during long-term use and 2-3 weeks after stopping treatment; manifested by diarrhea, leukocytosis, fever, abdominal pain (sometimes accompanied by the release of blood and mucus in the stool). If these phenomena occur, in mild cases, it is sufficient to discontinue treatment and use ion exchange resins (colestyramine, colestipol); in severe cases, replacement of the loss of fluid, electrolytes and protein, and the appointment of oral vancomycin or metronidazole are indicated. Do not use medications that inhibit intestinal motility.
The drug Biseptol 480 should not be used in the treatment of pharyngitis caused by beta-hemolytic streptococci from group A. The eradication of these bacteria in the nasopharynx with this drug is less effective than with the use of penicillin.
The administration of co-trimoxazole should be avoided in patients with established porphyria or in patients at risk of developing porphyria. Both trimethoprim and sulfonamides (although not specific to sulfamethoxazole) are associated with clinical exacerbations of porphyria.
Due to the propylene glycol content (2000 mg/5 ml), the drug may cause symptoms similar to those that occur after drinking alcohol.
One ampoule of the drug contains 12.4% vol. ethanol (alcohol), i.e. up to 500 mg/5 ml, which is equivalent to 11.88 ml beer or 4.95 ml wine. It is harmful for patients with alcohol disease. The alcohol content should be taken into account when using the drug in pregnant or breastfeeding women, children and patients at high risk, such as those with liver disease or epilepsy.
Biseptol 480 contains sodium disulfite (5 mg/5 ml), which in rare cases can cause severe hypersensitivity reactions and bronchospasm.
The drug Biseptol 480 contains sodium (39 mg/5 ml). This should be taken into account in patients on a controlled sodium diet.
Biseptol 480 contains two antibacterial components. The drug Biseptol 480 should be used only in cases where, in the opinion of the doctor, the expected benefit from its use exceeds any possible risk; the possibility of using single-component effective antibacterial drugs should be considered.
Biseptol suspension (vial 240mg/5ml 80ml)
A country
Poland
The country of production may vary depending on the batch of goods. Please check with the operator for detailed information when confirming your order.
Active substance
Co-trimoxazole [Sulfamethoxazole + Trimethoprim]
Compound
Bottle 80 ml
Sulfamethoxazole 200 mg, trimethoprim 40 mg per 5 ml. Excipients: macrogol glyceryl hydroxystearate, magnesium aluminosilicate, carmellose sodium, citric acid monohydrate, methylhydroxybenzoate, propylhydroxybenzoate, sodium saccharinate, sodium hydrogen phosphate dodecahydrate, maltitol, strawberry flavoring, propylene glycol, purified water. Suspension for oral administration is white or light cream in color, with a strawberry odor.
pharmachologic effect
Co-trimoxazole is a combined antimicrobial drug consisting of sulfamethoxazole and trimethoprim in a ratio of 5:1. Sulfamethoxazole, similar in structure to para-aminobenzoic acid (PABA), disrupts the synthesis of dihydrofolic acid in bacterial cells, preventing the inclusion of PABA in its molecule. Trimethoprim enhances the effect of sulfamethoxazole by interfering with the reduction of dihydrofolic acid to tetrahydrofolic acid, the active form of folic acid responsible for protein metabolism and microbial cell division. Both components thus disrupt the formation of folic acid, which is necessary for the synthesis of purine compounds by microorganisms, and then nucleic acids (RNA and DNA). This disrupts the formation of proteins and leads to the death of bacteria. In vitro it is a broad-spectrum bactericidal agent, but sensitivity may vary by geographic location. Typically susceptible pathogens (minimum inhibitory concentration (MIC) less than 80 mg/l for sulfamethoxazole): Moraxella (Branhamella) catarrhalis, Haemophilus influenzae (beta-lactamase-forming and beta-lactamase-non-forming strains), Haemophilus parainfluenzae, Escherichia coli (including enterotoxogenic strains), Citrobacter spp. (including Citrobacter freundii), Klebsiella spp. (including Klebsiella pneumoniae, Klebsiella oxytoca), Enterobacter cloaceae, Enterobacter aerogenes, Hafnia alvei, Serratia spp. (including Serratia marcescens, Serratia liquefaciens), Proteus mirabilis, Proteus vulgaris, Morganella morganii. Shigella spp. (including Shigella flexneri. Shigella sonnet). Yersinia spp. (including Yersinia enterocolitica), Vibrio cholerae, Edwardsiella tarda, Alcaligenes faecalis, Burkholderia (Pseudomonas) cepacia, Burkholderia (Pseudomonas) pseudomallei. Also, Brucella spp.. Listeria monocytogenes, Nocardia asteroides, Pneumocystis carinii, Cyclospora cayetanensis may be sensitive. Partially sensitive pathogens (MIC 80-160 mg/l for sulfamethoxazole): coagulase-negative strains of Staphylococcus spp. (including methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus). Streptococcus pneumoniae (penicillin-sensitive and penicillin-resistant strains), Haemophilus ducreyi, Providencia spp. (including Providencia rettgeri), Salmonella typhi. Salmonella enteritidis, Slenotrdphomonas maltophilia (formerly called Xanthomonas maltophilia), Acinetobacter Iwoffii, Acinetobacter baumanii, Aeromonas hydrophila. Resistant pathogens (MIC 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 the local characteristics of drug resistance of possible pathogens of a particular infectious disease. For infections that may be caused by partially susceptible microorganisms, it is recommended to conduct a sensitivity test to exclude pathogen resistance.
Indications for use
Infectious and inflammatory diseases caused by microorganisms sensitive to the drug: - respiratory tract infections: chronic bronchitis (exacerbation), Pneumocystis pneumonia (treatment and prevention) in adults and children; — infections of the ENT organs: otitis media (in children); - infections of the genitourinary organs: urinary tract infections, chancroid; — gastrointestinal infections: typhoid fever, paratyphoid fever, shigellosis (caused by sensitive strains of Shigella flexneri and Shigella sonnei); - travelers' diarrhea caused by enterotoxic strains of Escherichia coli, cholera (in addition to fluid and electrolyte replacement); - other bacterial infections (possibly combined with antibiotics): nocardiosis, brucellosis (acute), actinomycosis, osteomyelitis (acute and chronic), South American blastomycosis, toxoplasmosis (as part of complex therapy).
Side effects
From the nervous system: headache, dizziness, aseptic meningitis, peripheral neuritis, convulsions, ataxia, tinnitus, depression, hallucinations, apathy, nervousness. From the respiratory system: pulmonary infiltrates: eosinophilic infiltrate, allergic alveolitis (cough, shortness of breath). From the digestive system: nausea, vomiting, loss of appetite, diarrhea, gastritis, abdominal pain, glossitis, stomatitis, cholestasis, increased activity of liver transaminases, hepatitis (including cholestatic), hepatonecrosis, “vanishing bile duct” syndrome ( ductopenia), hyperbilirubinemia, pseudomembranous colitis, acute pancreatitis. From the hematopoietic organs: leukopenia, neutropenia, thrombocytopenia, hypoprothrombinemia, agranulocytosis, anemia (megaloblastic, hemolytic/autoimmune or aplastic), methemoglobinemia, eosinophilia. From the urinary system: interstitial nephritis, impaired renal function, hematuria, increased blood urea, hypercreatininemia, toxic nephropathy with oliguria and anuria, crystalluria. From the musculoskeletal system: arthralgia, myalgia, rhabdomyolysis (mainly in patients with AIDS). Allergic reactions: fever, angioedema, itching, photosensitivity, skin rash, urticaria, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, allergic myocarditis, conjunctival hyperemia , sclera, anaphylactic/anaphylactoid reactions, serum sickness, hemorrhagic vasculitis (Henoch-Schönlein purpura), periarteritis nodosa, lupus-like syndrome. Other: hyperkalemia (mainly in AIDS patients during treatment of Pneumocystis pneumonia), hyponatremia, hypoglycemia, weakness, fatigue, insomnia, candidiasis.
Contraindications
- liver and/or renal failure (creatinine clearance less than 15 ml/min);
- aplastic anemia, B12-deficiency anemia, agranulocytosis, leukopenia; - deficiency of glucose-6-phosphate dehydrogenase; - simultaneous use with dofetilide; - lactation period; - children up to 2 months or up to 6 weeks at birth from a mother with HIV infection; - hypersensitivity to sulfonamides, trimethoprim and/or other components of the drug. With caution: dysfunction of the thyroid gland, history of severe allergic reactions, bronchial asthma, folic acid deficiency, porphyria, pregnancy. Use during pregnancy and lactation During pregnancy, the drug should be prescribed only if the expected benefit from its use outweighs the possible risk to the fetus, since both trimethoprim and sulfamethoxazole cross the placental barrier and, thus, can affect the metabolism of folic acid. acids. In late pregnancy, the use of the drug should be avoided due to the possible risk of developing kernicterus in newborns. Due to the fact that trimethoprim and sulfamethoxazole pass into breast milk, the use of co-trimaxazole during lactation is contraindicated. Pregnant women receiving the drug are recommended to take 5 mg of folic acid per day.
Use in children Contraindicated: - children under 2 months of age or up to 6 weeks at birth from a mother with HIV infection. 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.
Use in elderly patients The duration of treatment should be as short as possible, especially in elderly and senile patients.
Mode of application
Inside, after eating with a sufficient amount of liquid. Adults and children over 12 years of age: - 960 mg every 12 hours; - for severe infections - 1440 mg every 12 hours; - for urinary tract infection - 10-14 days, for exacerbation of chronic bronchitis - 14 days, for traveler's diarrhea and shigellosis - 5 days. The minimum dose and dose for long-term treatment (more than 14 days) is 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 urinary tract infections and acute otitis media is 10 days, for shigellosis – 5 days. For severe infections, doses for children can be increased by 50%. For acute infections, the minimum duration of treatment is 5 days; after the symptoms disappear, therapy is continued for 2 days. If after 7 days of therapy there is no clinical improvement, the patient’s condition should be re-evaluated for possible treatment adjustment. Soft chancre - 960 mg every 12 hours; If after 7 days healing of the skin element does not occur, therapy can be extended for another 7 days. However, the lack of effect may indicate resistance of the pathogen. For women with acute uncomplicated urinary tract infections, a single dose of 1920-2880 mg is recommended, if possible in the evening after meals or before bed. For 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 of age - 960 mg/day. For children under 12 years of age - 450 mg/m2 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 instructions: for 0.26 m2 of body surface - 120 mg, respectively for 0.53 m2 - 240 mg, for 1.06 m2 - 480 mg. For other bacterial infections, the dose is selected individually depending on age, body weight, kidney function and severity of the disease, for example, for nocardiosis in adults - 2880-3840 mg/day for at least 3 months (sometimes up to 18 months). The course of treatment for acute brucellosis is 3-4 weeks, for typhoid fever and paratyphoid fever - 1-3 months.
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. During treatment, it is also inadvisable 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 disrupts 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. 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%. Effect on the ability to drive vehicles and operate machinery. Considering the possibility of developing significant side effects, during the treatment period it is necessary to be careful when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
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, IM - 5-15 mg/day of calcium folinate (eliminates the effect of trimethoprim on the bone marrow), if necessary - hemodialysis.
Interaction with other drugs
Increases the anticoagulant activity of indirect anticoagulants (anticoagulant dose adjustment), 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 (extends its T1/2 by 39%), increasing its effect and toxic effect. With simultaneous use of co-trimoxazole with pyrimethamine in doses exceeding 25 mg/week, the risk of developing megaloblastic anemia increases. Diuretics (usually thiazides and in elderly patients) increase the risk of thrombocytopenia. May increase serum digoxin concentrations, especially in elderly patients; monitoring of serum digoxin concentrations is necessary. The effectiveness of tricyclic antidepressants when taken in combination with co-trimoxazole may be reduced. Patients receiving co-trimoxazole and cyclosporine after kidney transplantation may experience a reversible deterioration in renal function, manifested by an increase in creatinine levels. Medicines that inhibit bone marrow hematopoiesis increase the risk of myelosuppression. When co-trimoxazole is used together with indomethacin, the concentration of sulfamethoxazole in the blood may increase. One case of toxic delirium has been described after simultaneous administration of co-trimoxazole and amantadine. When used simultaneously with ACE inhibitors, especially in elderly patients, hyperkalemia may develop. Trimethoprim, by inhibiting the renal transport system, increases the AUC of dofetilide by 103% and the Cmax of dofetilide by 93%. With increasing concentrations, dofetilide may cause ventricular arrhythmias with prolongation of the QT interval, including tachycardia. The simultaneous administration of dofetilide and trimethoprim is contraindicated.
Dispensing conditions in pharmacies
On prescription
