Co-trimoxazole tablets instructions for use. Release form and composition

Tablets 480 mg. 10 tablets in a blister pack.

1 or 2 packages with instructions for use in a cardboard box.

The drug is a broad-spectrum antibiotic. The product has proven effective against many known strains of bacteria. You can take Co-Trimoxazole only as prescribed by a doctor, since there is a high risk of side effects from the intestines, thyroid gland, circulatory, nervous systems and other organs.

Co-Trimoxazole - instructions for use

The drug should be used to treat infections only as prescribed by a doctor. The instructions for use indicate in detail the method of use and dosage, established in accordance with the age of the patient. These instructions must be followed to avoid adverse reactions and negative phenomena caused by the ingestion of excessive concentrations of medicinal substances into the body.

Composition and release form

The main components of the drug are sulfamethoxazole and trimethoprim, which have a bactericidal effect. The drug is dispensed in the form of tablets or suspension. The concentration of antibacterial substances depending on the form of the medication can be studied in the table:

Pharmacodynamics and pharmacokinetics

The medication is a combined antimicrobial drug with a bactericidal effect. The mechanism of action of the drug is based on blocking the synthesis of folates inside bacterial cells. The death of pathogenic microorganisms occurs due to the fact that sulfamethoxazole disrupts the formation of dihydrofolic acid, and trimethoprim increases disruptions in the formation of tetrahydrofolic acid, destroying proteins vital for the microbe.

Reactions occurring within the body increase the concentration of the drug in the blood plasma several hours after administration. Substances can pass through the placenta to the fetus and into breast milk. Metabolism of sulfonamides occurs in the liver. Metabolites do not have an antimicrobial effect. High antibacterial concentrations are found in urine. Substances are excreted by the kidneys and intestines.

Co-Trimoxazole - indications for use

The medicine can be used separately or as part of complex therapy. The drug Co-Trimoxazole is prescribed to patients for the treatment of the following ailments:

• bronchitis of acute and chronic forms;
• bronchiectasis;
• lobar, pneumocystis, bronchial pneumonia;
• salmonellosis, cholera;
• dysentery, typhoid fever, gastroenteritis;
• cholangitis, paratyphoid fever, cholecystitis;
• tonsillitis, scarlet fever, laryngitis;
• otitis media, sinusitis;
• gonorrhea, inguinal granuloma;
• prostatitis, urethritis;
• pyelitis, cystitis, pyelonephritis;
• furunculosis, pyoderma, severe wound infections.

Co-Trimoxazole is used as part of complex therapy together with other drugs. Combinations of medications are used in the treatment of diseases:

• toxoplasmosis;
• malaria;
• osteomyelitis (acute, chronic);
• osteoarticular infections;
• brucellosis in acute course;
• blastomycosis of South America.

Directions for use and dosage

The instructions for use say that the medicine is to be taken orally. You should take pills or suspension after meals or during meals. To prepare a mixture from granules, you need to add 100 ml of boiled water inside the bottle and mix the contents thoroughly. The duration of treatment depends on the established diagnosis. On average, drug therapy lasts up to 10 days.

Co-Trimoxazole – suspension

The dosage of the medicine is determined by the doctor according to the age and severity of the disease found in the patient. The drug Co-Trimoxazole in the form of a suspension is recommended to be taken in the following doses:

• infants under six months of age - 120 ml twice a day;
• children under 6 years old – 120-240 ml 2 times a day;
• children aged 6-12 years – 480 mg twice a day;
• adolescents and adults – 960 mg 2 times a day.

Co-Trimoxazole tablets

The instructions for the medicine provide a regimen for taking the drug in the form of pills. Experts establish the following dosage regimen for the use of tablets:

• adults and adolescents over 12 years of age are prescribed 960 mg once or 480 mg twice a day;
• for children under 2 years of age, 120 mg 2 times a day is indicated;
• children 2-5 years old – 120-240 mg twice a day;
• children 6-11 years old – 240-480 mg 2 times/day;
• for severe infection, adults are advised to take 480 mg three times a day;
• if the disease is chronic, the daily dose is 480 mg.

special instructions

If drug treatment is carried out for more than 30 days, the possibility of hematological changes increases. The transformations are reversible when the patient is given folic acid. This therapy does not have a significant effect on the effectiveness of the drug. Patients suffering from underlying folate deficiency should take the bactericidal agent with caution.

The drug must be discontinued if diarrhea or rash occurs. To prevent the development of crystalluria, urine output should be maintained in the required volumes. Side effects from taking antimicrobial sulfonamides can occur when the ability of the kidneys to eliminate harmful substances is impaired. During treatment with the drug, it is not recommended to eat greens, cauliflower, tomatoes, beans, carrots, or be exposed to strong ultraviolet radiation.

When treating AIDS patients, the risk of negative reactions increases. The drug is not prescribed for throat infections caused by group A beta-hemolytic streptococcus because strain resistance is widespread. Patients with pathologies of potassium metabolism and renal failure require periodic testing of blood plasma.

In childhood

The drug should be taken with caution in childhood. The dosage and regimen of use should be determined by the doctor, based on the diagnosis and the results of laboratory tests. Incorrect treatment of a child with sulfonamides can lead to the development of jaundice and hemolytic anemia. Treatment of diseases of infants with the drug is prohibited. An exception is the treatment of toxoplasmosis and Pneumocystis pneumonia.

Drug interactions

An antimicrobial drug can have a negative effect on the body when used simultaneously with the following drugs:

• Taking diuretics increases the possibility of developing thrombocytopenia and bleeding. This effect is often observed in older people. To determine the risk of thrombocytopenia in a timely manner, the patient must undergo regular examination.
• Co-administration with Cyclosporine after kidney transplantation may worsen the patient's condition.
• The activity of Warfarin and Phenytoin (anticoagulant drugs) in relation to liver metabolism is reduced.
• Barbiturates, Para-aminosalicylic acid and Phenytoin increase the activity of manifestations of folic acid deficiency.
• The effect of oral contraception is reduced.
• Drugs that are derivatives of salicylic acid enhance the effect of the drug Co Trimoxazole.
• The effect of indirect anticoagulants, the toxic concentration of Methotrexate, the effect of hypoglycemic drugs, and the antimicrobial activity of Chloridine increase.
• Rifampicin helps reduce the half-life of trimethoprim.
• Procaine, Benzocaine and their analogues can reduce the effectiveness of the drug.
• Concomitant use of the drug with Pyrimethamine can cause megaloblastic anemia.
• The use of cholestyramine reduces absorption. A break of several hours is recommended between taking medications.
• Drugs that inhibit the hematopoietic function of the spinal cord increase the risk of myelosuppression.
• Non-steroidal anti-inflammatory drugs (Indomethacin, Naproxen) can enhance the effect of sulfamethoxazole and trimethoprim.

Contraindications

The fight against diseases caused by bacteria using a combination of sulfamethoxazole and trimethoprim is strictly prohibited if the patient has the following factors:

• blood diseases (aplastic anemia, leukopenia, agranulocytosis);
• period of pregnancy and lactation;
• hypersensitivity to sulfonamides;
• deficiency of glucose-6-phosphate dehydrogenase (possible hemolysis of red blood cells);
• renal and liver failure;
• B12 deficiency anemia;
• up to 3 months of age.

In some diseases, the medicine can harm the body. Use with caution and under the supervision of a specialist is required for the following ailments:

• folic acid deficiency;
• diseases of the thyroid gland;
• high risk of allergies;
• bronchial asthma;
• dysfunction of the liver and kidneys.

Side effects

Using a bactericidal drug without a doctor's prescription and without conducting the necessary research may cause side effects. Symptoms appear in several body systems:

• Respiratory: pulmonary infiltrates, bronchospasms.
• Hematopoietic: neutropenia, anemia, polycythemia, leukopenia, agranulocytosis and other pathologies.
• Nervous: depression, tremor, peripheral neuritis, apathy, headache, ringing in the ears, dizziness.
• Digestive: hepatitis, cholestasis, abdominal pain, gastritis, stool disorders, vomiting and nausea, hepatonecrosis, enterocolitis, stomatitis, anorexia.
• Urinary: functional kidney disorders, polyuria, increased urea concentration, toxic nephropathy, accompanied by anuria, oliguria.
• Musculoskeletal system: myalgia, arthralgia.
• Allergic reactions are possible: toxic necrolysis of the epidermis, rash, elevated body temperature, hyperemia of the eye sclera, itching, dermatitis, erythema.

Overdose

Ingestion of sulfamethoxazole should be strictly according to the instructions or prescription of the doctor. Uncontrolled use of tablets or suspensions can lead to unpleasant, dangerous consequences of an overdose. An increase in the concentration of sulfamethoxazole is accompanied by the following symptoms:

• vomiting and feeling of nausea;
• formation of intestinal colic;
• dizziness and headache;
• confusion syndrome, depressive states, drowsiness;
• fainting;
• decreased visual acuity;
• hematuria;
• fever;
• crystalluria;
• thrombocytopenia;
• toxic jaundice;
• megaloblastic anemia;
• leukopenia.

These consequences of overdose must be quickly stopped in order to prevent the development of complications. Treatment is carried out through the following measures:

• withdrawal of medication;
• gastric lavage (carried out within no more than 2 hours after taking an excessive amount of medication);
• acidification of urine to remove trimethoprim;
• drinking plenty of water;
• forced diuresis;
• intramuscular administration of calcium folinate;
• hemodialysis.

Terms of sale and storage

The antimicrobial drug is dispensed from pharmacies only with a doctor's prescription. To purchase it, you should first seek advice from a specialist. The antibiotic must be stored in a dry, dark place out of reach of children. The shelf life of the granules is 2 years at temperatures up to 15 degrees. The finished mixture can be kept in the refrigerator for up to 1 month, in room conditions for up to 2 weeks. The shelf life of Co-Trimoxazole tablets is 5 years.

Analogs

The drug has a similar composition, properties and method of administration to some other drugs belonging to the sulfonamide group. Analogues of the drug are:

• Biseptol is a drug with a wide spectrum of antibacterial action. Shows activity in the fight against staphylococci, streptococci, E. coli and other pathogens. You can buy the drug in the form of tablets, syrup and concentrate for injection.
• Dvaseptol is a combined agent that has a bactericidal effect. The drug is used for urethritis, cystitis, gonorrhea, pneumonia and other diseases caused by bacterial activity. You can buy tablets, syrup, injection concentrate for adults and children.
• Metosulfabol is a combination drug that has a broad spectrum antimicrobial effect. The active substances are sulfamethoxazole and trimethoprim. Dispensed in ampoules according to a doctor's prescription.

Instructions for medical use

medicine

CO - TRIMOXAZOLE

Tradename

Co-trimoxazole

International nonproprietary name

No

Dosage form

Tablets 480 mg

Compound

One tablet contains

active substances: sulfamethoxazole 400 mg, trimethoprim 80 mg;

Excipients: potato starch, povidone, calcium stearate.

Description

Tablets are white or almost white, flat-cylindrical in shape, with a chamfer and a score.

Farmacotherapy group

Antibacterial drugs for systemic use. Sulfonamides and trimethoprim. Sulfonamides in combination with trimethoprim and its derivatives. Co-trimoxazole.

ATX code J01EE01

Pharmacological properties

Pharmacokinetics

After oral administration, trimethoprim and sulfamethoxazole are rapidly and almost completely absorbed. The maximum concentration when taken orally at a dose of 960 mg for sulfamethoxazole is achieved after 3.81 ± 2.49 hours and is 45.00 ± 13.92 mcg/ml, and for trimethoprim - after 2.25 ± 1.78 hours and is 1 .42±0.82 µg/ml. The antibacterial concentration is maintained for 7 hours. A steady state is achieved after 2-3 days of regular use.

In the blood, 42-46% of trimethoprim and about 66-70% of sulfamethoxazole are in a protein-bound state. Both substances easily penetrate through histohematic barriers into all organs and tissues; in the lungs and urine they create concentrations exceeding the level in plasma. Penetrates the blood-brain barrier and is found in high concentrations in the cerebrospinal fluid. Excreted in high concentrations in breast milk. The volume of distribution of sulfamethoxazole is 1.86 l/kg; trimethoprim - 0.29 l/kg. Metabolized in the liver. Sulfamethoxazole undergoes acetylation to form inactive metabolites, trimethoprim forms several oxymetabolites, some of which have weak antimicrobial activity.

Excreted by the kidneys. About 50-70% of trimethoprim and 10-30% of sulfamethoxazole are excreted unchanged. They are excreted in bile in small quantities. The elimination half-life for trimethoprim is about 10 hours, and for sulfamethoxazole it is about 11 hours.

In children, the elimination of co-trimoxazole is accelerated and depends on age: up to 1 year, the half-life periods of trimethoprim and sulfamethoxazole are 7 and 8 hours; at the age of 1-10 years - 5 and 6 hours, respectively. In persons over 60 years of age, as well as in persons with impaired renal function, the elimination of co-trimoxazole slows down.

Pharmacodynamics

The mechanism of action is associated with a disruption of the synthesis of nucleic acids in bacterial and protozoan cells. Co-trimoxazole does not have a negative effect on the synthesis of nucleic acids in human cells.

Highly active against gram-positive aerobic bacteria: Staphylococcus spp.(including beta-lactamase-producing strains) , Streptococcus spp. ( incl. Streptococcus pneumoniae, Streptococcus haemolyticus beta), Branchamella catarrhalis, Corynebacterium diphtheriae, Enterococcus faecalis, Listeria monocytogenes, Nocardia spp.; gram-negative aerobic bacteria: Escherichia coli, Enterobacter spp., Haemophilus spp., Klebsiella spp., Proteus spp., M. catarrhalis, Neisseria gonorrhoeae, Neisseria meningitidis, Providencia spp., Shigella spp., Salmonella spp., Serratia spp., S. maltophilia, Yersinia spp., V. cholerae.

Less active in relation to Acinetobacter spp., Actinomyces spp., Aeromonas hydrophila, Alcaligenes faecalis, Brucella spp., B. abortus, B. mallei, B. pseudomallei, Citrobacter spp., Chlamidia trachomatis, Cedecea spp., Edwardsiella spp., Hafnia alvei, Kluyvera spp. ., Legionella spp., Morganella morganii, Providencia spp.

Active against protozoa Pneumocystis carinii, Toxoplasma gondii, Plasmodium spp., Isospora belli, Isospora natalensis, Cyclosporidium cayetanensis, Cyclosporidium parvum.

Resistant to co-trimoxazole Pseudomonas aeruginosa(weak activity towards Pseudomonas cepacea), Campylobacter spp., Mycoplasma spp., Ureaplasma spp., M. tuberculosis, Leptospira, Borrelia, T. pallidum, rickettsia, pathogens of mycoses and viral infections. Currently, due to the development of resistance to the drug, there are significant fluctuations in the sensitivity of clinical species and strains of microorganisms.

Indications for use

• respiratory tract infections: chronic bronchitis (exacerbation), pneumonia caused by Pneumocystis carinii(treatment and prevention) in adults and children
• ENT infections: otitis media (in children)
• genitourinary infections: urinary tract infections, chancroid
• gastrointestinal tract infections: typhoid fever, paratyphoid shigellosis (caused by sensitive strains Shigellaflexneri And Shigellasonnei) , travelers' diarrhea caused by enterotoxic strains 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)

Directions for use and doses

The drug is taken orally after meals with a full glass (200 ml) of water. During treatment, you should monitor the consumption of a sufficient amount of fluid, and do not skip taking the next dose of the drug.

Adults and children over 12 years of age: 960 mg (2 tablets) 2 times a day every 12 hours. Daily dose - 4 tablets. In case of severe infection, you can increase the single dose to 1440 mg (3 tablets) 2 times a day every 12 hours.

Children from 6 to 12 years old - 480 mg every 12 hours, which approximately corresponds to a dose of 36 mg/kg/day.

Duration of treatment: for exacerbation of chronic bronchitis - 14 days, for traveler's diarrhea and shigellosis - 5 days, for typhoid fever and paratyphoid fever - 1-3 months, for chronic prostatitis - 3 months. The course of treatment for urinary infections and acute otitis media is 10 days. Soft chancroid - 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 acute infections, the minimum course of treatment is 5 days; after the symptoms disappear, therapy is continued for another 2 days. If after 7 days of therapy there is no clinical improvement, the causative agent should be clarified. The minimum dose and dose for long-term treatment (more than 14 days) is 480 mg every 12 hours.

When the course of treatment lasts more than 5 days and/or the dose of the drug is increased, it is necessary to monitor the peripheral blood picture; if pathological changes occur, tetrahydrofolic acid (calcium folinate, leucovorin) or folic acid should be prescribed at a dose of 5-10 mg/day.

When treating Pneumocystis pneumonia, sulfamethoxazole 100 mg/kg and trimethoprim 20 mg/kg per day are prescribed, every 6 hours for 14-21 days.

Prevention of Pneumocystis pneumonia - adults and children over 12 years of age: 960 mg (two tablets of 480 mg) once a day. Children from 6 to 12 years: 960 mg per day, divided into two equal doses every 12 hours for 3 days. The daily dose should not exceed 1920 mg (4 tablets of 480 mg).

Nocardiosis: adults usually take 6 to 8 tablets of Co-trimoxazole 480 mg per day. The course of treatment is 14 days. Then the dose is reduced and maintenance therapy is switched to for 3 months. The dose should be adjusted depending on the patient's age, body weight, renal function and severity of the disease.

For patients with a creatinine clearance of 15-30 ml/min, the dose should be reduced by 2 times; for patients with a creatinine clearance of less than 15 ml/min, the use of Co-trimoxazole is not recommended.

Elderly patients

The drug should be used with caution in elderly patients due to side effects, especially in patients with renal/liver impairment or taking other medications concomitantly.

In the absence of special instructions, standard doses of the drug should be taken.

Side effects

Often

Nausea, vomiting

Anorexia

Itching, rash, urticaria (mild and disappear quickly after discontinuation of the drug)

The frequency and severity of these adverse reactions are dose-dependent.

Not often (≥1/1000,<1/100)

Leukopenia, neutropenia and thrombocytopenia (most often mild or asymptomatic and disappear after discontinuation of the drug)

Rarely

Stomatitis, glossitis, diarrhea

Agranulocytosis, megaloblastic, hemolytic or aplastic anemia, methemoglobinemia, pancytopenia

Very rarely

Pseudomembranous enterocolitis

Fungal infections such as candidiasis

Hypersensitivity reactions, which manifest themselves as increased

body temperature, angioedema, anaphylactoid reactions and serum sickness, pulmonary infiltrates like eosinophilic or allergic alveolitis with cough or shortness of breath. If these symptoms suddenly appear or worsen, the patient should be re-examined and treatment should be stopped.

Progressive but reversible hyperkalemia, hyponatremia, hypoglycemia in persons without diabetes mellitus

Hallucinations

Neuropathy (including peripheral neuritis and paresthesia), uveitis

Increased transaminase activity and serum bilirubin levels, hepatitis, cholestasis, liver necrosis

Photosensitivity

Renal dysfunction, interstitial nephritis, increased blood urea nitrogen, serum creatinine, crystalluria, increased diuresis, especially in patients with cardiac edema

Arthralgia, myalgia

Described isolated cases nodular periarteritis and allergic myocarditis, aseptic meningitis or meningeal symptoms, ataxia, convulsions, dizziness, acute pancreatitis, however, such patients suffered from severe concomitant diseases, including AIDS, “vanishing bile duct” syndrome; isolated reports of cases of toxic epidermal necrolysis (Lyell's syndrome) and Henoch-Schönlein purpura, rhabdomyolysis. Isolated case reports of erythema multiforme and Stevens-Johnson syndrome have occurred (fatal) in several children receiving co-trimoxazole.

Adverse reactions in HIV-infected patients

The range of side effects in HIV-infected patients is the same as in the general population. However, some side effects are more common.

Often

Leukopenia, granulocytopenia and thrombocytopenia

Hyperkalemia

Increased body temperature, usually in combination with macular nodular

Often

Anorexia, nausea with or without vomiting, diarrhea

Increased transaminase levels

Maculo-nodular rash, usually accompanied by itching

Infrequently

• hyponatremia, hypokalemia

Contraindications

• hypersensitivity to sulfonamides, trimethoprim
• insufficiency of liver and kidney function (creatinine clearance less than 15 ml/min)
• B 12 - deficiency anemia, agranulocytosis, leukopenia, aplastic anemia
• glucose-6-phosphate dehydrogenase deficiency
• concomitant use of dofetilide
• pregnancy and lactation
• children up to 6 years old

Drug interactions

Increases serum concentrations of digoxin, especially in elderly patients (monitoring of serum digoxin concentrations is necessary). Reduces the effectiveness of tricyclic antidepressants.

When used together with non-steroidal anti-inflammatory drugs, antidiabetic drugs from the group of sulfonylurea derivatives (glibenclamide, glipizide, gliclazide, gliquidone), indirect anticoagulants and barbiturates, a mutual increase in the activity and toxicity of the drugs occurs.

Novocaine and benzocaine (anesthesin) reduce the antimicrobial activity of co-trimoxazole.

Methenamine (urotropine) and ascorbic acid contribute to the development of crystalluria when taking co-trimoxazole.

Pyrimethamine (more than 25 mg/week) increases the toxicity of co-trimoxazole when used together and the risk of developing macrocytic anemia.

When used simultaneously with combined oral contraceptives, it increases the risk of uterine bleeding and reduces the effectiveness of contraception.

When used together with phenytoin, there is an increase in the activity and toxicity of co-trimoxazole, a slowdown in the elimination of phenytoin with an increase in its toxicity.

When used simultaneously with rifampicin, the elimination of co-thymoxazole is accelerated.

Displaces methotrexate from binding with proteins and increases its toxic effects.

When used simultaneously with thiazide diuretics, the risk of developing thrombocytopenia increases (especially in elderly people).

In patients receiving cyclosporine A after kidney transplantation, co-trimoxazole causes reversible renal dysfunction.

Foods containing large amounts of folic acid: legumes, tomatoes, liver, kidneys reduce the antimicrobial activity of co-trimoxazole. In patients with Pneumocystis infection, it increases the likelihood of the pathogen developing resistance to co-trimoxazole.

Medicines that inhibit bone marrow hematopoiesis increase the risk of myelosuppression. When used simultaneously with indomethacin, an increase in the concentration of sulfamethoxazole in the blood is possible. A case of toxic delirium after simultaneous administration of co-trimoxazole and amantadine is described. When used simultaneously with ACE inhibitors, especially in elderly patients, hyperkalemia may develop. Trimethoprim, by inhibiting the renal transport system, increases AUC by 103%, Cmax by 93% of dofetilide, which increases the risk of developing ventricular arrhythmias with prolongation of the QT interval, including pirouette-type arrhythmias. Concomitant use of dofetilide and trimethoprim is contraindicated.

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.
During treatment with co-trimoxazole, it is necessary to take at least 2 liters of fluid per day and drink slightly alkaline mineral water to reduce the risk of urinary stone formation. During the treatment period, sun and UV irradiation should be avoided, as the risk of developing photodermatoses increases.

Use in persons with streptococcal infection. Co-trimoxazole should not be used as a first-choice drug in the treatment of persons with tonsillitis (tonsillitis), pharyngitis, and pneumococcal pneumonia.

Use with caution necessary when prescribing co-trimoxazole to patients with folic acid deficiency (elderly people, people suffering from alcohol dependence, malabsorption syndrome), porphyria, thyroid dysfunction, bronchial asthma and a history of allergic reactions. If skin rash or diarrhea occurs during treatment with co-trimoxazole, its use should be stopped immediately.

Long-term use. If long-term use of co-trimoxazole is necessary, hematological parameters of peripheral blood, functional state of the liver and kidneys should be monitored every 3 days. If there is a significant decrease in the content of formed elements in the blood or a change in biochemical parameters by more than 2 times, compared with normal limits, co-trimoxazole should be discontinued.

During treatment, it is not advisable to consume foods containing large quantities of PABA - green parts of plants (cauliflower, spinach, legumes), carrots, tomatoes.

If cough or shortness of breath suddenly appears or worsens, the patient should be re-examined and discontinuation of drug treatment should be considered. The risk of side effects increases significantly in patients with AIDS.

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 the blood 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.

In patients taking high doses of co-trimoxazole, serum potassium levels should be regularly monitored. Large doses of the drug for the treatment of Pneumocystis pneumonia can lead to a progressive but reversible increase in serum potassium in a significant number of patients. Hyperkalemia can be caused even by taking the recommended standard doses of the drug if it is prescribed against the background of impaired potassium metabolism, renal failure, or concomitant use of drugs that provoke hyperkalemia.

When treating with large doses of co-trimoxazole, the possibility of hypoglycemia should be considered, usually several days after the start of treatment. The risk of hypoglycemia is higher in patients with impaired renal function, liver disease, and malnutrition.

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 10%.

Pregnancy and lactation

The use of co-trimoxazole during pregnancy is contraindicated. If it is necessary to use the drug during lactation, the issue of stopping breastfeeding during treatment should be decided.

Use in pediatrics

Features of the effect of the drug on the ability to drive vehicles and potentially dangerous mechanisms

During the treatment period, care must be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: in case of acute overdose, nausea, vomiting, intestinal colic, diarrhea, headache, dizziness, visual disturbances, drowsiness, depression, fainting, confusion, fever are observed. In severe cases - crystalluria, hematuria, anuria. With prolonged intoxication, inhibition of hematopoiesis is observed, manifested by thrombocytopenia, leukopenia, megaloblastic anemia; jaundice.

Treatment: drug withdrawal, forced diuresis with urine alkalization. Acidification of the urine increases the excretion of trimethoprim but may increase the risk of crystallization. In severe cases - hemodialysis. Symptomatic therapy. A specific antidote is folinic acid (calcium folinate or leucovorin) 3-10 mg intramuscularly once a day for 5-7 days.