A typical clinical and pharmacological article
This information is a reference and it is not enough that the drug was prescribed by a doctor. .
PHARMACHOLOGIC EFFECT
Combined antimicrobial drug consisting of sulfamethoxazole and trimethoprim. Sulfamethoxazole, similar in structure to para-aminobenzoic acid (PABA), disrupts the synthesis of dihydrofolic acid in bacterial cells, preventing the incorporation of PABA into its molecule. Trimethoprim enhances the action of sulfamethoxazole, disrupting the reduction of dihydrofolic acid into a tetrahydrofolic - active form of folic acid, responsible for protein metabolism and division of the microbial cell.
It is a broad-spectrum bactericidal drug that is active against the following microorganisms: Streptococcus spp. (haemolytic strains are more susceptible to penicillin), Staphylococcus spp., Streptococcus pneumoniae, Neisseria meningitidis, Neisseria gonorrhoeae, Escherichia coli (including enterotoxigenic strains), Salmonella spp.(including Salmonella typhi and Salmonella paratyphi), Vibrio cholerae, Bacillus anthracis, Haemophilus influenzae (including ampicillin-resistant strains), Listeria spp., Nocardia asteroides, Bordetella pertussis, Enterococcus faecalis, Klebsiella spp., Proteus spp., Pasteurella spp., Francisella tularensis , Brucella spp., Mycobacterium spp. (including Mycobacterium leprae), Citrobacter, Enterobacter spp., Legionella pneumophila, Providencia, some species of Pseudomonas (except Pseudomonas aeruginosa), Serratia marcescens, Shigella spp., Yersinia spp., Morganella spp., Pneumocystis carinii; Chlamydia spp. (including Chlamydia trachomatis, Chlamydia psittaci); protozoa: Plasmodium spp., Toxoplasma gondii, pathogenic fungi, Actinomyces israelii, Coccidioides immitis, Histoplasma capsulatum, Leishmania spp.
Resistant to the drug: Corynebacterium spp., Pseudomonas aeruginosa, Mycobacterium tuberculosis, Treponema spp., Leptospira spp., Viruses.
Inhibits the vital activity of E. coli, which leads to a decrease in the synthesis of thymine, riboflavin, nicotinic acid, and other vitamins of group B in the intestine.
PHARMACOKINETICS
When taken orally, absorption is 90%. T Cmax is 1-4 hours, the therapeutic concentration level is maintained for 7 hours after a single dose. Well distributed in the body. It penetrates the GEB, the placental barrier and into breast milk. In the lungs and urine creates concentrations exceeding the content in the plasma. To a lesser extent, it accumulates in bronchial secretion, vaginal secretions, secretion and prostate tissue, middle ear fluid (with its inflammation), cerebrospinal fluid, bile, bones, saliva, watery eyes, breast milk, interstitial fluid. The connection with plasma proteins is 66% in sulfamethoxazole, in trimethoprim 45%.
More sulfamethoxazole is metabolized with the formation of acetylated derivatives. Metabolites do not have antimicrobial activity.
It is excreted by the kidneys in the form of metabolites (80% within 72 hours) and unchanged (20% sulfamethoxazole, 50% trimethoprim); a small amount - through the intestine. T 1/2 sulfamethoxazole - 9-11 h, trimethoprim - 10-12 h, in children - significantly less and depends on age: up to 1 year - 7-8 h, 1-10 years - 5-6 h. In the elderly and patients with impaired renal function T 1/2 increases.
INDICATIONS
- Urinary tract infections: urethritis, cystitis, pyelitis, pyelonephritis, prostatitis, epididymitis, gonorrhea (male and female), mild chancroid, venereal lymphogranuloma, inguinal granuloma;
- respiratory tract infections: bronchitis (acute and chronic), bronchiectasis, croupous pneumonia, bronchopneumonia, pneumocystis pneumonia;
- ENT-organs infections: otitis media, sinusitis, laryngitis, tonsillitis; scarlet fever;
- Gastrointestinal infections: typhoid fever, paratyphoid, salmonella, cholera, dysentery, cholecystitis, cholangitis, gastroenteritis caused by enterotoxic strains of Escherichia coli;
- skin and soft tissue infections: acne, furunculosis, pyoderma, wound infections;
- osteomyelitis (acute and chronic), etc. osteoarticular infections, brucellosis (acute), South American blastomycosis, malaria (Plasmodium falciparum), toxoplasmosis (as part of complex therapy).
DOSING MODE
Inside, in / in, / m. In each dosage form, the quantitative ratio of trimethoprim and sulfamethoxazole is 1: 5.
Inside ( tablets ), adults and children over 12 years - 960 mg once, or 480 mg 2 times a day. In severe infections - 480 mg 3 times a day, with chronic infections, amaintenance dose of 480 mg 2 times a day. Children 1-2 years - 120 mg 2 times a day, 2-6 years - 120-240 mg 2 times a day, 6-12 years - 240-480 mg 2 times a day.
Suspension : children 3-6 months - 120 mg twice a day, 7 months-3 years - 120-240 mg twice a day, 4-6 years - 240-480 mg twice a day, 7-12 years - 480 mg 2 times a day, adults and children over 12 years - 960 mg 2 times a day. Syrup for children: children 1-2 years - 120 mg 2 times a day, 2-6 years - 180-240 mg 2 times a day, 6-12 years - 240-480 mg 2 times a day.
The minimum duration of treatment is 4 days; After the disappearance of symptoms, therapy is continued for 2 days. With chronic infections, the course of treatment is longer. With acute brucellosis - 3-4 weeks, with typhoid fever and paratyphoid - 1-3 months.
To prevent the recurrence of chronic urinary tract infections, adults and children over 12 years of age - 480 mg once a day at night, children under 12 years - 12 mg / kg / day. Duration of treatment - 3-12 months. The course of treatment of acute cystitis in children 7-16 years - 480 mg 2 times a day for 3 days.
With gonorrhea - 1920-2880 mg / day for 3 doses.
With gonorrheal pharyngitis (with hypersensitivity to penicillin) - 4320 mg once a day for 5 days. In pneumonia caused by Pneumocystis carinii , 120 mg / kg / day with an interval of 6 hours for 14 days.
Parenteral: in / m adults and children over 12 years - 480 mg every 12 hours, children 6-12 years - 240 mg every 12 hours.
In / in drip , adults and children over 12 years - 960-1920 mg every 12 hours, children 6-12 years - 480 mg 2 times a day; 6 months-5 years - 240 mg 2 times a day; 6 weeks to 5 months - 120 mg 2 times a day.
To achieve maximum efficacy, a constant concentration of trimethoprim in plasma or serum should be maintained at 5 Ојg / ml or higher.
Malaria caused by Plasmodium falciparum is an intravenous infusion (1920 mg twice daily) for 2 days. Children will need a correspondingly reduced dose.
To achieve higher concentrations in CSF, I / drip (dissolved in 200 ml of solvent) for 1 hour 2 times a day.
In case of renal insufficiency, the dose depends on the value of CC: with a QC greater than 25 ml / min - the standard dose; at 15-25 ml / min - the standard dose for 3 days, then half the standard dose. When QC is less than 15 ml / mint, half the standard dose is prescribed only against hemodialysis.
Dissolve in the following proportions immediately before administration: 480 mg (5 ml infusion solution) for 125 ml, 960 mg (10 ml) for 250 ml, 1440 mg (15 ml) for 500 ml infusion solution.
If there is clouding or crystallization of the solution before or during infusion, the mixture can not be used. The duration of administration is 1-1.5 hours (should be consistent with the needs of the patient in the liquid).
If necessary, the restriction in the volume of the injected liquid is introduced at higher concentrations - 5 ml is dissolved in 50-75 ml of a 5% solution of dextrose in water. In severe infections in all age groups, the dose can be increased by 50%.
SIDE EFFECT
From the side of the nervous system: headache, dizziness; in some cases - aseptic meningitis, depression, apathy, tremor, peripheral neuritis.
On the part of the respiratory system: bronchospasm, pulmonary infiltrates.
On the part of the digestive system: nausea, vomiting, decreased appetite, diarrhea, gastritis, abdominal pain, glossitis, stomatitis, cholestasis, increased activity of "hepatic" transaminases, hepatitis, hepatonecrosis, pseudomembranous enterocolitis.
On the part of the hematopoiesis: leukopenia, neutropenia, thrombocytopenia, agranulocytosis, megaloblastic anemia.
From the urinary system: polyuria, interstitial nephritis, renal dysfunction, crystalluria, hematuria, increased urea concentration, hypercreatininaemia, toxic nephropathy with oliguria and anuria.
From the musculoskeletal system: arthralgia, myalgia.
Allergic reactions: itching, photosensitivity, rash, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, allergic myocarditis, fever, angioedema, hyperemia sclera.
Local reactions: thrombophlebitis (in place of venipuncture), tenderness at the site of administration.
Other: hypoglycemia.
CONTRAINDICATIONS
- hypersensitivity (including sulfanilamides);
- liver failure;
- renal failure (CC less than 15 ml / min);
- Aplastic anemia;
- B 12 -deficient anemia;
- agranulocytosis, leukopenia;
- deficiency of glucose-6-phosphate dehydrogenase;
- Pregnancy;
- lactation period;
- age up to 6 years (for the / m introduction);
- Children's age (up to 3 months - for oral administration);
- Hyperbilirubinemia in children.
With caution : deficiency of folic acid, bronchial asthma, thyroid gland diseases.
PREGNANCY AND LACTATION
Contraindicated in pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
In case of renal insufficiency, the dose depends on the value of CC: with a QC greater than 25 ml / min - the standard dose; at 15-25 ml / min - the standard dose for 3 days, then half the standard dose. When QC is less than 15 ml / mint, half the standard dose is prescribed only against hemodialysis.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in liver failure.
APPLICATION FOR CHILDREN
For children, the drug is prescribed according to the indications and according to the recommended dosage regimen. In / m administration is contraindicated at the age of up to 6 years, ingestion - children up to 3 months.
APPLICATION IN ELDERLY PATIENTS
In the elderly and patients with impaired renal function, T 1/2 increases.
SPECIAL INSTRUCTIONS
It is desirable to determine the concentration of sulfamethoxazole in the plasma every 2-3 days just before the next infusion. If the concentration of sulfamethoxazole exceeds 150 Ојg / ml, treatment should be interrupted until it falls below 120 Ојg / ml.
With long (more than a month) treatment courses, regular blood tests are necessary, since there is a possibility of hematological changes (most often asymptomatic).These changes can be reversible in the appointment of folic acid (3-6 mg / day), which does not significantly violate the antimicrobial activity of the drug. Particular caution should be shown in the treatment of elderly patients or patients with a suspected initial lack of folate. The purpose of folic acid is also suitable for long-term treatment in high doses.
For the prevention of crystalluria it is recommended to maintain a sufficient volume of excreted urine. The likelihood of toxic and allergic complications of sulfonamides significantly increases with a decrease in the filtration function of the kidneys.
It is also inappropriate to use food products containing large quantities of PABC, green parts of plants (cauliflower, spinach, beans), carrots, tomatoes.
Excessive sunlight and UV irradiation should be avoided.
The risk of side effects is much higher in patients with AIDS.
It is not recommended for use in tonsillitis and pharyngitis caused by beta-hemolytic streptococcus group A, due to widespread resistance of strains.
OVERDOSE
Symptoms: nausea, vomiting, intestinal colic, dizziness, headache, drowsiness, depression, fainting, confusion, visual impairment, fever, hematuria, crystalluria; with prolonged overdose - thrombocytopenia, leukopenia, megaloblastic anemia, jaundice.
Treatment: gastric lavage, acidification of urine increases the excretion of trimethoprim, intake of fluid inside, in / m - 5-15 mg / day of calcium folinate (eliminates the effect of trimethoprim on the bone marrow), if necessary - hemodialysis.
DRUG INTERACTION
Pharmaceutically compatible with the following medicines: dextrose for IV infusions 5 and 10%, levulosis for IV infusions 5%, sodium chloride for IV infusions 0.9%, a mixture of 0.18% sodium chloride and 4% dextrose for IV infusions, 6% dextran 70 for IV infusions in 5% dextrose or in 0.9% sodium chloride solution, 10% dextran 40 for IV infusions in 5% dextrose or 0.9% sodium chloride solution, Ringer's injection.
Increases the anticoagulant activity of indirect anticoagulants, as well as the effect of hypoglycemic drugs and methotrexate.
Reduces the intensity of hepatic metabolism of phenytoin (prolongs its T 1/2 by 39%) and warfarin, enhancing their effect.
Reduces the reliability of oral contraception (inhibits the intestinal microflora and reduces the intestinal-hepatic circulation of hormonal compounds).
Rifampicin reduces T 1/2 trimethoprim.
Pyrimethamine in doses exceeding 25 mg / week increases the risk of megaloblastic anemia.
Diuretics (often thiazides) increase the risk of thrombocytopenia.
Reduce the effect of benzocaine, procaine, procainamide (and other medicines, as a result of hydrolysis of which formed PABC).
Between diuretics (thiazides, furosemide, etc.) and oral hypoglycemic drugs (sulfonylureas), on the one hand, and antimicrobial sulfonamides, on the other, it is possible to develop a cross-allergic reaction.
Phenytoin, barbiturates, PASC intensify manifestations of folic acid deficiency.
The derivatives of salicylic acid intensify the action.
Kolestyramine lowers absorption, so it should be taken 1 hour after or 4-6 hours before taking co-trimoxazole.
Drugs that depress bone marrow hematopoies, increase the risk of myelosuppression.
