Biseptol oral suspension 240 mg/5 ml bottle 80 ml

Instructions Biseptol oral suspension 240 mg/5 ml bottle 80 ml

Composition

active ingredients: sulfamethoxazole/trimethoprim;

5 ml of suspension contain sulfamethoxazole 200 mg, trimethoprim 40 mg;

excipients: polyethylene glycol (macrogol) hydroxystearate, carmellose sodium, aluminum-magnesium silicate, citric acid monohydrate, sodium hydrogen phosphate dodecahydrate, methyl parahydroxybenzoate (E 218), propyl parahydroxybenzoate (E 216), liquid maltitol, sodium saccharin, strawberry flavoring (flavoring substances, propylene glycol), propylene glycol, purified water.

Dosage form

Oral suspension.

Main physicochemical properties: white or light cream suspension with a strawberry odor.

Pharmacotherapeutic group

Antimicrobials for systemic use; combination of sulfonamides and trimethoprim and its derivatives. ATX code J01E E01.

Pharmacological properties

Pharmacodynamics

The antibacterial activity of co-trimoxazole in vitro extends to both Gram-positive and Gram-negative pathogens, including the following microorganisms, although susceptibility may vary by geographical area.

Usually susceptible pathogens (MIC (minimum inhibitory concentration) 90 ≤ 2 mg/l [trimethoprim]; ≤ 38 mg/l [sulfamethoxazole])

Cocci: Moraxella catarrhalis.

Gram-negative rods: Haemophilus parainfluenzae, Citrobacter freundii, other Citrobacter spp., Klebsiella oxytoca, other Klebsiella spp., Enterobacter cloacae, Enterobacter aerogenes, Hafnia alvei, Serratia marcescens, Serratia liquefaciens, other Serratia spp., Yersinia enterocolitica, other Yersinia spp., Vibrio cholerae.

Various gram-negative bacilli: Edwardsiella tarda, Alcaligenes faecalis, Burkholderia pseudomallei.

Based on clinical experience, the following pathogens are also considered susceptible: Brucella, Listeria monocytogenes, Nocardia asteroides, Pneumocystis jiroveci (P.carinii), Cyclospora cayetanensis.

Partially susceptible pathogens (MIC 90 = 4 mg/l [trimethoprim]; = 76 mg/l [sulfamethoxazole])

Cocci: Staphylococcus aureus (methicillin-susceptible and methicillin-resistant), Staphylococcus spp. (coagulase-negative), Streptococcus pneumoniae (penicillin-susceptible, penicillin-resistant).

Gram-negative rods: Haemophilus influenzae (β-lactamase positive, β-lactamase negative), Haemophilus ducreyi, E. coli, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, other Providencia spp., Salmonella typhi, Salmonella enteritidis, Stenotrophomonas maltophilia (formerly Xanthomonas maltophilia).

Various gram-negative bacilli: Acinetobacter lwoffi, Acinetobacter anitratus (especially A. baumanii), Aeromonas hydrophila.

Resistant pathogens (MIC 90 ≥ 8 mg/L [trimethoprim]; ≥ 152 mg/L [sulfamethoxazole])
Burkholderia (Pseudomonas) cepacia, Pseudomonas aeruginosa, Mycoplasma spp., Mycobacterium tuberculosis, Shigella spp., Treponema pallidum, Neisseria gonorrhoeae, Bacteroides, other exclusively anaerobic pathogens.

When using Biseptol on an empirical basis, it is necessary to take into account the local prevalence of resistance to co-trimoxazole among the bacteria causing the infection being treated.

In infections caused by moderately susceptible pathogens, susceptibility testing should be performed to exclude resistance.

Susceptibility to co-trimoxazole can be determined using standard methods such as the disk method or the dilution method recommended by the Clinical and Laboratory Standards Institute (CLSI). The CLSI recommends the use of the following susceptibility criteria:

Disk: 1.25 mcg of trimethoprim and 23.75 mcg of sulfamethoxazole.

** Trimethoprim (TM) and sulfamethoxazole (SMZ) in a ratio of 1 to 19.

Development of resistance, cross-resistance

Resistance to cotrimoxazole develops during treatment only in rare cases. There is cross-resistance between all sulfonamides; cross-resistance to chemically unrelated antibiotics does not develop as a result of resistance to cotrimoxazole.

Synergism, antagonism

There is a pronounced synergism between sulfamethoxazole and trimethoprim. This synergism is manifested in most cases even in the presence of resistance to one of the two components of the drug.

Pharmacokinetics

In terms of clinically relevant pharmacokinetic properties, trimethoprim and sulfamethoxazole are largely similar.

Absorption

After oral administration of trimethoprim and sulfamethoxazole, these drugs are rapidly and almost completely absorbed (bioavailability 80–100%) in the upper digestive tract. After a single dose of 160 mg of trimethoprim + 800 mg of sulfamethoxazole, the maximum plasma concentration of 1.5–3 mg/l for trimethoprim and 40–80 mg/l for sulfamethoxazole is reached within 1–4 hours. If the dose is repeated every 12 hours, the equilibrium plasma concentration of sulfamethoxazole and trimethoprim is in most cases 50–100% higher than after a single oral dose. The level in the blood plasma is proportional to the dose. The effect of food on the kinetics of the active substances of Biseptol has not been studied. When trimethoprim suspension is taken after a meal, absorption is less than when taken on an empty stomach, although the rate of absorption is not affected by regular food.

Distribution

At the above concentrations, 42–46% of trimethoprim and 66% of sulfamethoxazole bind to blood plasma proteins.

Animal and human studies have shown that co-trimoxazole penetrates well into tissues. A significant amount of trimethoprim and a small amount of sulfamethoxazole pass from the circulation into the interstitial fluid and other extravascular fluids of the body. The concentration of trimethoprim and sulfamethoxazole may be increased in inflamed tissues.

Trimethoprim and sulfamethoxazole have been detected in the fetal placenta, cord blood, amniotic fluid, and fetal tissues (liver, lungs), indicating that these substances cross the placental barrier. Trimethoprim concentrations are generally close to those in the maternal circulation, while sulfamethoxazole levels are lower in the fetus.

Both substances pass into breast milk. The concentration in breast milk is close in value (trimethoprim) or lower (sulfamethoxazole) compared to the concentration of the drug in the mother's blood plasma.

Metabolism

About 50–70% of a dose of trimethoprim and 10–30% of sulfamethoxazole are excreted unchanged in the urine. The main metabolites of trimethoprim are the 1- and 3-oxides and the 3'- and 4'-hydroxy derivatives; some of the metabolites are active. Sulfamethoxazole is metabolized in the liver primarily by N4-acetylation and to a lesser extent by glucuronidation; its metabolites are inactive.

Breeding

Under normal renal function, the half-lives of both components are very similar in value (on average 10 hours for trimethoprim and 11 hours for sulfamethoxazole).

The total clearance rate is about 100 ml/min for trimethoprim and 20 ml/min for sulfamethoxazole.

The half-life of trimethoprim in children is approximately half that of adults, while no significant differences are observed with respect to sulfamethoxazole.

Both substances and their metabolites are excreted primarily by the kidneys, both by glomerular filtration and tubular secretion. The concentration of trimethoprim and sulfamethoxazole in the urine is approximately 100 and 5 times higher than the corresponding concentration in the blood plasma.

Renal clearance is 20–80 mL/min for trimethoprim and 1–5 mL/min for sulfamethoxazole.

Both substances are found in feces in small amounts.

Pharmacokinetics in special patient groups

In elderly patients, as well as in patients with impaired renal function, the half-lives of both components of the drug increase, which necessitates the need for appropriate dose adjustment.
Although the kinetics, especially of trimethoprim, in patients with impaired liver function do not undergo significant changes, caution is indicated when using Biseptol in high doses in severe liver dysfunction. Determination of the drug level in the blood and dose correction are necessary when using hemodialysis.

Indication

Infections caused by microorganisms sensitive to co-trimoxazole, namely:

Upper and lower respiratory tract infections and ear infections: exacerbation of chronic bronchitis, bronchiectasis, pneumonia (including pneumonia caused by Pneumocystis jiroveci), sinusitis, otitis media; genitourinary system infections: acute and chronic cystitis, pyelonephritis, urethritis, prostatitis; gastrointestinal tract infections, including typhoid and paratyphoid fever (including treatment of chronic carriers) and cholera (as an adjunct to fluid and electrolyte replacement); other bacterial infections caused by susceptible microorganisms: acute brucellosis, nocardiosis, actinomycetoma (except those caused by true fungi), South American blastomycosis (Paracoccidioides brasiliensis).

In osteomyelitis - as a last-line drug (for example, if vancomycin is contraindicated), if the sensitivity of multiresistant pathogens to cotrimoxazole has been proven.

Official recommendations for the appropriate use of antibiotics should be followed, especially recommendations for use to prevent the increase in antibiotic resistance.

Contraindication

Hypersensitivity to the active substances, to sulfonamides or trimethoprim or to any of the excipients. Severe parenchymal liver disease. Severe renal impairment (creatinine clearance < 15 ml/min) if it is not possible to periodically determine the concentration of trimethoprim and sulfamethoxazole in the blood plasma. Megaloblastic anemia due to folate deficiency. Immune thrombocytopenia caused by the use of trimethoprim and/or sulfonamides. Hematological disorders. Combination with dofetilide. Glucose-6-phosphate dehydrogenase deficiency. Should not be used in children under 2 months of age. Porphyria. Last trimester of pregnancy and breastfeeding.

Interaction with other medicinal products and other types of interactions

Increased blood digoxin levels may develop during concomitant treatment with co-trimoxazole, especially in elderly patients.

Close supervision of such patients is necessary, and phenytoin plasma levels should be monitored.

The effectiveness of tricyclic antidepressants may be reduced with concomitant use of cotrimoxazole.

Sulfonamides, including sulfamethoxazole, can displace methotrexate from plasma protein binding sites and impair the renal transport of methotrexate, thereby increasing the concentration of free methotrexate and enhancing its effects.

Cotrimoxazole may affect the need for oral antidiabetic agents.

Like other antibiotics, Biseptol may reduce the effectiveness of oral contraceptives. Therefore, patients should be advised to use additional contraceptive measures during treatment with Biseptol.

Concomitant administration of indomethacin and cotrimoxazole may increase the level of sulfamethoxazole in the blood.

An increased incidence of thrombocytopenia with purpura has been observed in elderly patients concomitantly taking certain diuretics, mainly thiazide diuretics.

Cotrimoxazole has been reported to prolong prothrombin time in patients taking the anticoagulant warfarin (sulfamethoxazole may displace warfarin from its binding to plasma albumin). This interaction should be considered when using Biseptol in patients already taking anticoagulants. In such cases, it is necessary to regularly check prothrombin time and monitor blood clotting time in patients.

Reversible deterioration of renal function, as measured by increased serum creatinine levels, has been observed in patients receiving co-trimoxazole and ciclosporin following renal transplantation. This interaction is thought to be mediated by trimethoprim.

Cases of pancytopenia have been reported in patients receiving a combination of trimethoprim and methotrexate (see section 4.4). Trimethoprim has a low affinity for human dihydrofolate reductase and may potentiate the adverse effects of methotrexate, leading to adverse haematological interactions with methotrexate, particularly in the presence of other risk factors such as advanced age, hypoalbuminaemia, renal impairment and reduced bone marrow reserve. These adverse reactions may occur particularly with high doses of methotrexate.

Such patients should be given folic acid or calcium folinate to counteract the effects on hematopoiesis (emergency treatment).

Individual reports indicate that patients taking pyrimethamine-containing drugs for the prevention of malaria in doses exceeding 25 mg pyrimethamine per week may develop megaloblastic anemia while taking co-trimoxazole.

Cases of toxic delirium have been reported after concomitant administration of Biseptol and amantadine.

There is evidence that trimethoprim may interact with dofetilide by inhibiting the renal transport system. Coadministration of trimethoprim 160 mg with sulfamethoxazole 800 mg twice daily and dofetilide 500 mcg twice daily for 4 days resulted in a 103% increase in the area under the concentration-time curve (AUC) and a 93% increase in the maximum plasma concentration (Cmax). Dofetilide may cause serious ventricular arrhythmias associated with QT prolongation, including torsades de pointes, which are directly related to plasma dofetilide concentrations. Concomitant administration of dofetilide and trimethoprim is contraindicated.

Caution should be exercised if the patient is taking other drugs that may cause hyperkalemia.

Also, concomitant use of trimethoprim/sulfamethoxazole (cotrimoxazole) and spironolactone may lead to clinically significant hyperkalemia.

Concomitant use with co-trimoxazole may increase the systemic exposure of medicinal products that are primarily metabolised by CYP2C8, including paclitaxel, amiodarone, dapsone, repaglinide, rosiglitazone and pioglitazone.

Paclitaxel and amiodarone have a narrow therapeutic index. If a patient is receiving paclitaxel or amiodarone, consideration should be given to using an alternative antibiotic.
Both dapsone and cotrimoxazole can cause methemoglobinuria. Patients receiving dapsone in combination with cotrimoxazole should be monitored for methemoglobinuria. Alternative treatments should be used if possible.

Impact on laboratory parameters

Biseptol, namely trimethoprim, which is part of it, may affect the results of determination of methotrexate concentration in serum, carried out by the method of competitive binding to proteins using bacterial dihydrofolate reductase as a ligand. However, when determining methotrexate by the radioimmunoassay method, no interference occurs.

Biseptol may alter the reaction of creatinine determination using alkaline picrate according to the Jaffe method (increases creatinine levels by approximately 10%). Functional disorders of tubular secretion of creatinine may give a false decrease in creatinine clearance.

Co-administration of co-trimoxazole at a dose of 160 mg trimethoprim and 800 mg sulfamethoxazole causes a 40% increase in lamivudine exposure (due to trimethoprim). Lamivudine does not affect the pharmacokinetics of trimethoprim and sulfamethoxazole.

Application features

Biseptol should be used with caution in patients with a history of allergies or bronchial asthma.

Depending on the dose and duration of treatment, the risk of serious adverse reactions may be increased in elderly patients, patients with comorbid conditions such as impaired liver and/or kidney function, and patients taking other medications at the same time. Although rare, fatal outcomes have been reported in association with adverse reactions, namely persistent pathological changes in the cellular composition of the blood (dyscrasias), Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), and fulminant hepatic necrosis.

Life-threatening reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN)) have been reported with sulfamethoxazole. The patient should be informed of the signs and symptoms of skin reactions and the need for close monitoring for this reaction. The greatest risk of developing skin changes associated with Stevens-Johnson syndrome and toxic epidermal necrolysis occurs during the first weeks of treatment with the drug.

If cutaneous symptoms of Stevens-Johnson syndrome or toxic epidermal necrolysis (e.g., bullous skin eruptions or enanthemas) occur, sulfamethoxazole should be discontinued.

The best treatment outcomes for Stevens-Johnson syndrome and toxic epidermal necrolysis are achieved with early diagnosis and immediate discontinuation of the suspected product. Early diagnosis is associated with a better prognosis.

If a patient has been diagnosed with Stevens-Johnson syndrome or toxic epidermal necrolysis, sulfamethoxazole should not be re-administered.

Rare cases of life-threatening complications associated with the use of sulfonamides have been described, including: Stevens-Johnson syndrome, TEN, acute liver necrosis, agranulocytosis, megaloblastic anemia and other bone marrow lesions, as well as hypersensitivity from the respiratory tract.

Except in exceptional cases, Biseptol should not be prescribed to patients with serious persistent changes in the cellular composition of the blood. From time to time, the drug has been prescribed to patients receiving cytotoxic agents for the treatment of leukemia, without any signs of side effects on the bone marrow or peripheral blood.

Due to the possibility of hemolysis, Biseptol should not be prescribed to patients with certain hemoglobinopathies (Hb-Zurich, Hb-Cologne), except in cases of extreme necessity and only in minimal doses.

Treatment should be discontinued immediately at the first appearance of skin rashes or any other serious adverse reactions.

To minimize the risk of adverse reactions, the duration of treatment with Biseptol should be as short as possible, particularly in elderly patients. In case of impaired renal function, the dosage should be adjusted in accordance with the dosage instructions set out in the section "Method of administration and dosage".

In AIDS patients receiving cotrimoxazole for the treatment of Pneumocystis jiroveci infection, adverse reactions such as rash, fever, leukopenia, increased serum aminotransferase levels, hypokalemia, and hyponatremia are more common.
Severe persistent diarrhea during or after treatment may indicate pseudomembranous colitis, which requires urgent treatment. In such cases, it is necessary to stop taking Biseptol and initiate appropriate diagnostic and therapeutic measures (for example, prescribe vancomycin 250 mg 4 times a day orally). Antiperistaltic drugs are contraindicated in such cases.

If Biseptol is taken for a long period of time (longer than 14 days), regular complete blood count is necessary. Folic acid should be considered during treatment, but the possible effect on antibacterial efficacy should be taken into account.

In rare cases, usually in debilitated patients, crystals in the urine have been observed with the use of sulfonamides.

During long-term treatment, renal and urinary function should be monitored, especially in patients with impaired renal function.

To prevent the development of crystalluria during treatment, adequate fluid intake and diuresis should be ensured.

Crystals have been reported rarely in fresh urine, but have been observed in cooled urine of patients during treatment. Patients with hypoalbuminuria may be at increased risk of crystal formation.

Since Biseptol, like other antibiotics, may reduce the effect of oral contraceptives, patients should be advised to use additional contraceptive measures during treatment with Biseptol.

Prolonged treatment with Biseptol may lead to overgrowth of non-susceptible microorganisms and fungi. In case of superinfection, appropriate treatment should be initiated immediately.

Caution is required when treating patients with porphyria or thyroid dysfunction.

Caution is required when treating patients with additional risk factors for folic acid deficiency, such as treatment with phenytoin or other folic acid antagonists and malnutrition.

Cases of pancytopenia have been reported in patients receiving the combination of trimethoprim and methotrexate (see section 4.5).

Trimethoprim has been shown to have an adverse effect on phenylalanine metabolism. However, this does not apply to patients with phenylketonuria who follow an appropriate diet.

Individuals with "slow acetylation" are at increased risk of idiosyncratic reactions to sulfonamides.

In patients at risk of hyperkalemia and hyponatremia, careful monitoring of potassium and sodium in the blood plasma is warranted. Concomitant use of drugs that cause hyperkalemia and spironolactone may lead to severe hyperkalemia.

Use should be avoided in patients at risk or suspected of developing porphyria. The use of trimethoprim and sulfamethoxazole has been associated with exacerbation of porphyria. Since it contains

The excipients include liquid maltitol, so patients with rare hereditary problems of fructose intolerance should not take this medicine. Liquid maltitol may have a mild laxative effect.

The medicine contains methyl parahydroxybenzoate and propyl parahydroxybenzoate, therefore it may cause allergic reactions (possibly delayed).

The medicine contains polyethylene glycol (macrogol) hydroxystearate, so it may cause headache, gastrointestinal irritation and diarrhea.

This medicinal product contains 38 mg sodium per 5 ml. Caution should be exercised when used in patients on a controlled sodium diet.

Ability to influence reaction speed when driving vehicles or other mechanisms

Biseptol usually does not have a direct effect on the ability to drive or use machines. However, there is a possibility of undesirable effects on the nervous system and psyche that may affect this ability, in some cases to a significant extent (see section "Adverse reactions").

Use during pregnancy or breastfeeding

Pregnancy

Trimethoprim and sulfamethoxazole cross the placental barrier; their safety in pregnant women has not been established.
Trimethoprim is a folic acid antagonist, and in animal studies, high doses of cotrimoxazole have been shown to cause malformations. Controlled clinical studies have shown a possible association between the use of folic acid antagonists and congenital malformations in humans, and therefore the drug is not recommended during pregnancy, especially in the first trimester, unless the expected benefit to the mother outweighs the risk to the fetus. If the drug is prescribed during pregnancy, folic acid should be considered.

Use in the third trimester of pregnancy is contraindicated (see section "Contraindications").

Sulfamethoxazole competes with bilirubin for binding to plasma albumin, resulting in significant amounts of the drug crossing the placental barrier and remaining in the newborn's blood for several days. This may lead to the development and exacerbation of hyperbilirubinemia and associated kernicterus if the drug is administered to the mother within a few days of delivery. This theoretical risk is of particular importance in neonates at increased risk of hyperbilirubinemia, such as premature infants or infants with glucose-6-phosphate dehydrogenase deficiency.

Breast-feeding

Since trimethoprim and sulfamethoxazole pass into breast milk, breastfeeding while taking Biseptol is not recommended. If the use of the drug is necessary, breastfeeding should be discontinued.

Method of administration and doses

Biseptol should be taken every 12 hours. Biseptol is best taken after a meal with plenty of fluids. In acute infections, Biseptol should be prescribed for a period of at least 5 days.

The drug should be administered orally.

Shake before use until a homogeneous suspension is obtained.

5 ml of suspension contain 200 mg of sulfamethoxazole and 40 mg of trimethoprim.

A graduated measuring cup is included with the bottle.

Children and adolescents

2–5 months – 2.5 ml (morning and evening) every 12 hours; 6 months – 5 years – 5 ml twice a day every 12 hours; 6–12 years – 10 ml twice a day every 12 hours; Over 12 years – 20 ml twice a day every 12 hours.

The dosage regimen corresponds approximately to a daily dose of 6 mg trimethoprim and 30 mg sulfamethoxazole per 1 kg of body weight. In severe infections, the dose may be increased by 50%.
Adults

Take 20 ml of suspension every 12 hours.

The minimum dose for adults and adolescents aged 12 years and over, as well as for long-term treatment (longer than 14 days), is 10 ml of suspension every 12 hours.

In particularly difficult cases of infection – 30 ml of suspension every 12 hours.

Dosage in special cases.

Pneumonia caused by Pneumocystis jiroveci.

The maximum dose, depending on the patient's body weight, is determined according to the table:

For the prevention of pneumonia caused by Pneumocystis jiroveci, adults should be prescribed 800 mg of sulfamethoxazole and 160 mg of trimethoprim. For children, a dose of 150 mg/m2/day of trimethoprim and 750 mg/m2/day of sulfamethoxazole is recommended, which is administered in 2 equal doses for 3 consecutive days.
The total daily dose should not exceed 320 mg of trimethoprim and 1600 mg of sulfamethoxazole. In this case, the following recommendations can be followed:

Dosage for patients with renal impairment.

Patients on hemodialysis
If Biseptol is indicated for patients on hemodialysis, it should be taken initially in the standard dose, then half or third of the standard dose every 24–48 hours. It is necessary to ensure monitoring of the drug's serum concentration and appropriate dose adjustment.

Children

The drug can be used in children from 2 months of age.

Biseptol should not be prescribed to premature babies, as well as newborns during the first 2 months of life due to the increased risk of kernicterus (bilirubin encephalopathy).

Overdose

Symptoms of acute overdose: nausea, vomiting, diarrhea, colic, headache, vertigo, dizziness, drowsiness, loss of consciousness, confusion, fever, intellectual and visual disorders, jaundice, changes in blood composition, in severe cases - crystalluria, hematuria and anuria.

Symptoms of chronic overdose: inhibition of hematopoiesis (thrombocytopenia, leukopenia, megaloblastic anemia), as well as other pathological changes in the blood picture due to folic acid deficiency.

Treatment (depending on symptoms): gastric lavage, use of drugs that induce vomiting, increased renal excretion by forced diuresis (alkalinization of urine promotes the excretion of sulfamethoxazole), hemodialysis (peritoneal dialysis is ineffective). It is necessary to monitor the blood picture and electrolyte levels. In case of pronounced pathological changes in the blood picture or jaundice, specific treatment is prescribed. To eliminate the effect of trimethoprim on hematopoiesis, calcium folinate can be prescribed in a dose of
3–6 mg intramuscularly for 5–7 days.

Adverse reactions

The main adverse reactions are skin reactions and mild gastrointestinal disorders, which occur during treatment in approximately 5% of cases.
Infections and parasitic diseases: fungal infections, namely candidiasis.

From the blood and lymphatic system: leukopenia, granulocytopenia, thrombocytopenia, eosinophilia, agranulocytosis, anemia (megaloblastic, immunohemolytic, aplastic), methemoglobinemia, pancytopenia, neutropenia, polycythemia, hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency. The most frequently observed changes in the blood were mild, asymptomatic and reversible after discontinuation of the drug.

On the part of the immune system: allergic reactions, namely fever, drug fever, angioedema, urticaria, anaphylactoid reactions and serum sickness, periarteritis nodosa, allergic vasculitis, allergic myocarditis, exfoliative dermatitis, systemic lupus erythematosus, hypersensitivity reactions.

Metabolic and nutritional disorders: Elevated serum potassium - In a significant proportion of patients with Pneumocystis jiroveci pneumonia, high doses of trimethoprim cause a progressive but reversible increase in serum potassium. In patients with impaired potassium metabolism or renal failure or in those receiving drugs that induce hyperkalemia, trimethoprim can very commonly cause hyperkalemia (in more than 60% of patients), even when used at recommended doses. In such patients, careful monitoring of potassium levels is necessary.

Hyponatremia

Hypoglycemia in non-diabetic patients usually occurs within the first few days of treatment. Patients with renal impairment, liver disease, or malnutrition, as well as those taking high doses of trimethoprim-sulfamethoxazole, are at particular risk.

Psychiatric: hallucinations, depression, apathy, insomnia, increased fatigue, sleep disturbances. Delirium and psychosis, particularly in elderly patients.

Respiratory: pneumonitis with eosinophilic infiltration, dyspnea, cough, shallow breathing, pulmonary infiltrates. Cough, shallow breathing, pulmonary infiltrates may be early indicators of respiratory hypersensitivity, which very rarely had a fatal outcome.

Gastrointestinal: nausea (with or without vomiting), anorexia, stomatitis, glossitis, gingivitis, diarrhea, pseudomembranous enterocolitis, acute pancreatitis in seriously ill patients, gastritis, abdominal pain.

From the hepatobiliary system: increased levels of transaminases and bilirubin, hepatitis, cholestasis, jaundice, liver necrosis, bile duct obliterating syndrome, fulminant hepatitis, inflammation of the liver parenchyma.

Skin: rash. These side effects are in most cases mild and disappear quickly after discontinuation of the drug.

As with other sulfonamide-containing drugs, very rare adverse reactions include erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), purpura, Henoch-Schonlein purpura, photosensitivity. Not known: Drug rash with eosinophilia and systemic symptoms (DRESS)

Musculoskeletal system: arthralgia, myalgia, rhabdomyolysis.

Renal and urinary disorders: renal dysfunction and renal failure, oliguria, anuria, interstitial nephritis, increased blood urea nitrogen, increased serum creatinine, crystalluria. Sulfonamides, including Biseptol, may increase diuresis, particularly in patients with edema due to cardiovascular disease.

The product contains methyl parahydroxybenzoate (E 218) and propyl parahydroxybenzoate (E 216), which may cause allergic reactions (possibly delayed).
Adverse effects in HIV-infected patients: HIV-infected patients with frequent comorbidities and their treatment usually receive long-term prophylaxis or treatment of pneumonia caused by Pneumocystis jiroveci with the use of high doses of Biseptol. Apart from a small number of additional side effects, the side effect profile in such patients is similar to that in the population of patients who are not HIV-infected. However, some side effects are observed more often (in approximately 65% of patients) and are often more severe, which necessitates the interruption of treatment with Biseptol in 20-25% of patients.

In particular, the following adverse reactions were observed in addition or with a higher frequency:

From the blood and lymphatic system: mainly neutropenia, but also anemia, leukopenia, granulocytopenia and thrombocytopenia, agranulocytosis.

Immune system disorders: fever, usually associated with skin rashes, allergic reactions such as angioedema, anaphylactoid reactions and serum sickness, hypersensitivity reactions.

Metabolism and nutrition disorders: hyperkalemia. In such patients, careful monitoring of serum potassium levels is necessary; hyponatremia, hypoglycemia.

Psychiatric disorders: acute psychosis.

Nervous system: neuropathy (including peripheral neuritis and paresthesia), hallucinations, uveitis. Aseptic meningitis or meningitis-like symptoms, ataxia, convulsions, Parkinson-like resting tremor, sometimes combined with apathy, leg cramps and shuffling gait, vertigo, tinnitus.

Respiratory: pneumonitis with eosinophilic infiltration.

On the part of the digestive tract: anorexia, nausea with or without vomiting, as well as diarrhea, stomatitis, glossitis, pancreatitis.

Hepatobiliary system: increased liver enzymes/liver enzymes