Co-trimoxazole

Co-trimoxazole is a combined antibacterial drug . Co-trimoxazole is a chemotherapeutic agent with a wide spectrum of bactericidal action due to the blocking of folate biosynthesis in microbial cells: sulfamethoxazole disrupts the synthesis of dihydrofolic acid , and Trimethoprim prevents the conversion of dihydrofolic acid to tetrahydrofolic acid.

The activity of the drug is manifested in relation to almost all groups of microorganisms: gram-negative - Salmonella spp., Shigella spp., Neisseria spp., Proteus vulgaris , Vibrio cholerae , Yersinia spp., Escherichia coli ; gram-positive - Staphylococcus spp., Corynebacterium and others. Chlamydia , actinomycetes , and Klebsiella are also sensitive to the drug.

The activity of co-trimoxazole against pneumocystis Pneumocystis carinii , an important causative agent of pneumocystic pneumonia in weakened, immunodeficient patients, especially HIV-infected patients, is of great clinical importance.

Pharmacokinetics

When administered, both components of the drug are completely absorbed from the gastrointestinal tract. The maximum concentration of the active components of the drug is observed after 1-4 hours. Trimethoprim differs in good penetration into cells and through tissue barriers - into the lungs, kidneys, prostate, bile, saliva, sputum, cerebrospinal fluid. The binding of trimethoprim to proteins of 50%, its half-life is normal from 8.6 to 17 hours. The main route of elimination of trimethoprim is through the kidneys, 50% unchanged. Sulfamethoxazole: its binding to plasma proteins is 66%, the half-life from 9 to 11 hours is normal. The main route of elimination is the kidneys, moreover, from 15 to 30% in active form.

The drug is used to treat infections: the respiratory tract ( bronchitis , pneumonia , lung abscess , pleural empyema , otitis media , sinusitis ), meningitis, brain abscess, urogenital system ( pyelonephritis , urethritis , salpingitis , prostatitis ), including gonorrheal nature, gastrointestinal intestinal ( dysentery , cholera , typhoid fever , paratyphoid , diarrhea ), skin and soft tissues ( pyoderma , furunculosis , etc.).

Hypersensitivity to trimethoprim and / or sulfonamides, pregnancy, newborns up to 6 weeks of life, severe cardiac, hepatic, renal and hematological diseases, glucose-6-phosphate dehydrogenase deficiency.

Precautions in childhood.

The drug is taken orally after a meal with a sufficient amount of liquid. The dose is prescribed individually. Children from 2 to 5 years: 2 tablets (120 mg) 2 times a day. Children from 6 to 12 years: 4 tablets (120 mg) or 1 tablet (480 mg) 2 times a day. With pneumonia - 100 mg / kg / day (based on sulfamethoxazole), the interval between doses is 6 hours, the course of treatment is 14 days. With gonorrhea - 2 g of sulfamethoxazole 2 times a day with an interval of 12 hours. Adults and children over 12 years of age: 960 mg 2 times a day, with prolonged therapy 480 mg 2 times a day. The duration of the course of treatment is from 5 to 14 days. In severe cases and / or in the chronic form of infectious diseases, a single dose increase of 30-50% is permissible.

In the case of prolonging the course of treatment for more than 5 days and / or increasing the dose, it is necessary to conduct hematological control; in case of a change in the blood picture, an additional appointment of folic acid at 5-10 mg per day is necessary.

• From the organs of the gastrointestinal tract - gastritis, dyspepsia, nausea, vomiting, anorexia, rarely - cholestatic and necrotic hepatitis, increased levels of transaminases and bilirubin, pseudo-membranous enterocolitis, pancreatitis, stomatitis, glossitis.
• On the part of the hematopoietic organs - agranulocytosis, aplastic anemia, thrombocytopenia, hemolytic anemia, megaloblastic anemia, hypothrombinemia, methemoglobinemia, eosinophilia.
• From the urinary system - crystallurgy, renal failure, interstitial nephritis, increased plasma creatine levels. Toxic nephropathy with oligouria and anuria.
• Allergic reactions - urticaria, rash, toxic epidermal necrolysis (Lyell syndrome), Steven-Johnson syndrome, allergic myocarditis, erythema multiforme, exfoliative dermatitis, Quincke edema, itching, redness of the sclera, fever.
• Others - hyperkalemia, hyponatremia, aseptic meningitis, peripheral neuritis, headache, depression, arthralgia, myalgia, weakness, photosensitivity

Symptoms - anorexia, nausea, vomiting, weakness, abdominal pain, headache, drowsiness, hematuria, crystalluria, blurred consciousness. Measures taken: drug withdrawal, gastric lavage (no later than 2 hours after taking an excessive dose), heavy drinking, forced diuresis, calcium folate (5-10 mg / day), if necessary, hemodialysis.

The drug is not recommended to be taken simultaneously with thiazide diuretics due to the risk of thrombocytopenia (bleeding). Co-trimoxazole enhances the anticoagulant activity of warfarin and anticonvulsant phenytoin. Trimethoprim potentiates the action of antidiabetic drugs of sulfonylurea derivatives. Rifampicin shortens the half-life of trimethoprim. The combined use of co-trimoxazole and cyclosporine after kidney surgery worsens the condition of patients. The simultaneous administration of the drug with salicylates, butadione, naproxen and derivatives of para-aminobenzoic acid is not recommended.

With caution, a drug is prescribed for folic acid deficiency in the body, bronchial asthma , a burdened allergic history .

Store in a dry, dark place. Keep out of the reach of children. Shelf life 5 years. Do not use an expired drug.

In connection with the undesirable effects of co-trimoxazole, a special public committee was created in the UK, according to which 130 deaths associated with the use of the drug were recorded. The most dangerous are serious, potentially fatal skin reactions (mucocutaneous febrile syndromes) - toxic epidermal necrolysis syndrome (Lyell syndrome) and Stevens-Johnson syndrome. When sulfonamides and co-trimoxazole are used, the relative risk of their development is approximately 10–20 times higher than when using b-lactam antibiotics [3].

The use of co-trimoxazole requires careful monitoring of undesirable drug reactions, the underestimation of which can lead to death. From the microbiological, clinical and pharmacoeconomic points of view, with the vast majority of common infections that have traditionally been indications for the use of co-trimoxazole, monotherapy with trimethoprim or antibiotics of other groups should be preferred

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