Co-trimoxazole – a combined antimicrobial, belonging to the group of sulfonamides.
Co-trimoxazole chemotherapeutic agent with a broad spectrum bactericidal action due to the blocking of biosynthesis of folate in microbial cells: testosterone cypionate vs propionate digidrofolevoy violates the synthesis of acid and trimethoprim prevents the conversion of dihydrofolate tetrahydrofolic acid. Both components are thus disrupt the formation of folic acid required for the synthesis of purine compounds by microorganisms, and then the nucleic acids (RNA and DNA). This disrupts the formation of proteins and results in the death of the bacteria.
Drug activity shown against nearly all groups of microorganisms: Staphylococcus aureus, Staphylococcus saprophyticus, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus viridans, and Pneumocystis carinii, Salmonella spp, (including Salmonella typhi and Salmonella. paratyphi), Shigella spp., Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Enterobacter spp., Serratia spp., Escherichia coli, Haemophilus influenzae, Morganella morganii, Yersinia spp., Brucella spp., Neisseria meningitidis, Neisseria gonorrhoeae, (including enterogenous strains), Vibrio cholerae, Bacillus anthracis, Listeria spp., Nocardia asteroides, Bordetella pertussis, Enterococcus faecalis, Pasteurella spp., Francisella tularensis, Brucella spp., Mycobacterium spp. (includingMycobacterium leprae ), Citrobacter, Enterobacter spp, Legionella pneumopnia, Providencia,. some species of Pseudomonas (except Ps.aeruginosa ) major viruses – of Chlamydia spp. (including of Chlamydia trachomatis, of Chlamydia psittaci ), the simplest: Plazmodium spp, with Toxoplasma gondii,. pathogenic fungi, – of Actinomyces . israelii, Coccidioides immitis, Histoplasma capsulatum
, Leishmania spp resistant to the drug: Corynebacterium spp, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Treponema spp, Leptospira spp,… viruses.
Inhibits vital activity of Escherichia coli, which leads to a decrease of synthesis of thiamin, riboflavin, nicotinic acid and others. B vitamins in the intestine.
When administered orally, the two components of the drug absorbed from the gastrointestinal tract of 90%. The therapeutic level of concentration of active substances in the blood and tissues is set at 60 minutes after administration and is maintained for 12 hours. The maximum plasma concentration is reached after 4.1 hours. The drug is well distributed in the body. It penetrates the GEB, placental barrier and into breast milk. The lungs and urine concentrations creates excess in plasma. To a lesser extent accumulate in bronchial secretions, vaginal secretions, secretions and prostate tissue, middle ear fluid, cerebrospinal fluid, bile, bone, saliva, the aqueous humor of the eye, breast milk, interstitial fluid.
Contact with plasma proteins – 66% for testosterone cypionate vs propionate, trimethoprim at – 45%. testosterone cypionate vs propionate and trimethoprim is metabolized in the liver. Mostly testosterone cypionate vs propionate is metabolised to produce acetylated derivatives. Metobolity not have antimicrobial activity.
Excreted by the kidneys as metabolites (80% for 72 hours) and in unchanged form (20% testosterone cypionate vs propionate, trimethoprim 50%); a small amount – through the intestines. T 1/2 testosterone cypionate vs propionate – 9-11 hours, trimethoprim – 10-12 hours, at children – significantly less, depending on age: up to the first year – 7-8 hours, 1-10 years – 5-6 hours and Older. patients with impaired renal function T 1/2 increases.
The drug is used to treat diseases caused by susceptible to malaria infections:
- respiratory tract infections: bronchitis (acute and chronic), bronchiectasis, lobar pneumonia, bronchopneumonia, Pneumocystis pneumonia, empyema, lung abscess,
- infection of upper respiratory tract: otitis media, sinusitis, laryngitis, tonsillitis, pharyngitis, tonsillitis; scarlet fever,
- urinary organs infections: pyelonephritis, pyelitis, epididymitis, cystitis, urethritis, salpingitis, prostatitis, gonorrhea (male and female), chancroid, lymphogranuloma venereum, granuloma inguinale,
- Gastrointestinal infections: dysentery, cholera, typhoid, paratyphoid, salmonellonositelstvo, cholera, cholecystitis, cholangitis, gastroenteritis caused by E. coli strains enterotoksichnymi, skin and soft tissue infections: acne, furunculosis, pyoderma, abscesses and wound infections,
And also: osteomyelitis (acute and chronic), brucellosis (acute), sepsis, peritonitis, meningitis, brain abscess, osteoarticular infections, South American blastomycosis, malaria (Plasmodium falciparum), whooping cough (in the complex therapy).
Hypersensitivity to trimethoprim and / or sulfonamides, pregnancy, breastfeeding, children under 3 months of age, deficiency of glucose-6-phosphate dehydrogenase, liver and / or renal insufficiency (creatinine clearance less than 15 ml / min), aplastic anemia, in 12 -scarce anemia, agranulocytosis, leukopenia, hyperbilirubinemia in children.
with care apply at deficiency of folic acid, asthma, thyroid disease.
Dosing and Administration
The drug is taken during or immediately after a meal with plenty of fluids. Before use, stir until a homogeneous suspension.
5 ml of the suspension contains 200 mg testosterone cypionate vs propionate and 40 mg trimethoprim. The pack is attached to the scale of measurement.
Children generally used from 20 mg to 30 mg of testosterone cypionate vs propionate and from 4 mg to 6 mg of trimethoprim per 1 kg of body weight per day.
|from 3 months
to 6 months (6-8 kg)
|from 7 months
to 3 years (9-15 kg)
|4 year of age
to 6 years (16-22 kg)
|7 year of age
up to 12 years (23-42 kg)
|2.5 ml||every 12 hours|
|2.5-5 ml||every 12 hours|
|5.10 ml||every 12 hours|
|10 ml||every 12 hours|
Adults and children over 12 years – 20 ml every 12 hours.
The duration of treatment 5 to 14 days. In severe and / or chronic infections is acceptable increase in a single dose by 30-50%.
The drug is taken during or after a meal. In the course of treatment is recommended to drink plenty of liquids. In case of extension of the course of treatment for more than 5 days and / or increasing the dose necessary to carry out haematological monitoring; in the case of changes in the blood picture of folic acid is necessary for the purpose of 5-10 mg per day.
Usually the drug is well tolerated. In some cases, there are headaches, depression, lethargy, dizziness, tremor, aseptic meningitis, peripheral neuritis.
The respiratory system: bronchospasm, pulmonary infiltrates. From the digestive system: anorexia, gastritis, abdominal pain, glossitis, stomatitis, cholestasis, increased activity of “liver” transaminases, rarely – hepatitis, pseudomembranous enterocolitis.
From the side of hematopoiesis: thrombocytopenia, neutropenia, rarely – agranulocytosis, megablastnaya anemia.
From the urinary excretory system: polyuria, interstitsilny nephritis, renal failure, crystalluria, hematuria, elevated levels of urea, hypercreatininemia, toxic nephropathy with oliguria and anuria from the musculoskeletal system:. arthralgia, myalgia.
Allergic reactions: itching, photosensitivity, rash, increase in body temperature, redness of the sclera, in some cases – polymorphonuclear bullous erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis Lyell, eksfolialny dermatitis, allergic myocarditis, angioedema.
Symptoms include nausea, vomiting, confusion, fainting, intestinal colic, dizziness, headache, drowsiness, depression, blurred vision, fever, hematuria, crystalluria; For prolonged overdose – thrombocytopenia, leukopenia, megaloblastic anemia, jaundice.
Treatment: removal of the drug, gastric lavage (no later than 2 hours after the overdose), acidification of urine increases the excretion of trimethoprim, drinking plenty of fluids, in / m – 5-15 mg / day folinic acid (eliminates the effect of trimethoprim on the bone marrow), the forcing of diuresis, if necessary – hemodialysis.
During long-term treatment need regular blood tests, because there is the risk of hematological changes (often asymptomatic).
Caution should be exercised when administering the drug to the liver or kidney failure (if creatinine clearance 15-30 ml / min. Is recommended to take half the usual dose). Particular caution should be exercised when treating elderly patients or patients with suspected initial lack of folate. Folic acid is also advisable Assignment prolonged treatment at high dosages. Precautions to take for patients with allergic reactions in the anamnesis. The appearance of skin rash or severe course of diarrhea is an indication for discontinuation of the drug.
To prevent crystalluria is recommended to maintain adequate urine output. The likelihood of toxic and allergic complications sulfonamides increases significantly with a decrease in the filtration function of kidneys. It is inappropriate and against the background of treatment to use foods that contain large amounts of PABA – green parts of plants (cauliflower, spinach, beans), carrots, tomatoes. Avoid excessive sun and UV radiation.
Biseptolum may interfere with the creatinine determination reaction using an alkali pikrinata Jaffe (creatinine level increases by approx. 10%). The risk of side effects is much higher in patients with AIDS.
Not recommended for pharyngitis and tonsillitis caused by beta-hemolytic streptococcus group A because of widespread resistance strains of.
Pregnancy and lactation
The drug should not be used during pregnancy and breastfeeding, as a means to cross the placenta and is excreted in breast milk.
Interaction with Drug
The drug is not recommended to take in conjunction with thiazide diuretics because of the risk of thrombocytopenia (bleeding). Increases the anticoagulant activity of indirect anticoagulants, increases the effects of hypoglycemic agents and methotrexate. Co-trimoxazole reduces the intensity of the hepatic metabolism of phenytoin (extends its T 1/2 at 39%) and warfarin, increasing their effect. Pyrimethamine at doses exceeding 25 mg / week, increases the risk of megaloblastic anemia. Reduce the effect of benzocaine, procaine, procainamide (et al. PM, as a result of which a PLBK hydrolysis). Between diuretics (thiazides, furosemide et al.) And oral hypoglycemic drugs (sulfonylurea derivatives) on the one hand and antimicrobial sulfonamides – the other may develop allergic cross-reaction. Phenytoin, barbiturates, Pasco increase the expression of folate deficiency. Salicylic acid derivatives enhance the effect. Ascorbic acid, hexamethylenetetramine (et al. PM, acidifying the urine) increases the risk of crystalluria.Cholestyramine reduces the absorption, it should be taken 1 hour after or 4-6 hours before receiving co-trimoxazole. Reduces the reliability of oral contraceptives (inhibits the intestinal microflora and reduces the enterohepatic circulation of hormonal compounds).
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Rifampicin reduces the half-life of trimethoprim. Combined appointment of cotrimoxazole and cyclosporin after operations on the kidneys worsen the condition of patients.
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