Ко-тримоксазол-Акри®

General characteristics. Structure:

Active ingredients: 0,1 g or 0,4 g of sulfamethoxazole, 0,02 g or 0,08 g of Trimethoprimum in 1 tablet.

Excipients: potato starch, magnesium stearate, polyvinylpirrolidone.

Pharmacological properties:

Pharmacodynamics. The combined antimicrobic drug consisting of sulfamethoxazole and Trimethoprimum. The sulfamethoxazole similar on a structure to paraaminobenzoic acid (PABK), breaks synthesis of dihydrofolic acid in bacterial cells, interfering with inclusion of PABK in its molecule. Trimethoprimum strengthens effect of sulfamethoxazole, breaking recovery of dihydrofolic acid in tetrahydrofolic — the active form of folic acid responsible for protein metabolism and division of a microbic cell.

Is bactericidal drug of a broad spectrum of activity, it is active concerning the following microorganisms: Streptococcus spp. (hemolitic strains are more sensitive to penicillin), Staphylococcus spp., Streptococcus pneumoniae, Neisseria meningitidis, Neisseria gonorrhoeae, Escherichia coli (including enterotoksogenny 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 pneumopnia, Providencia, some types of Pseudomonas (except Ps. aeruginosa), Serratia marcescens, Shigella (flexneri and sonnei), Yersinia spp., Morganella spp. Pneumocystis carini; large viruses — Chlamydia spp. virus (including Chlamydia trachomatis, Chlamydia psittaci); protozoa: Plasmodium spp., Toxoplasma gondii, pathogenic fungi, Actinomyces israelii, Coccidioides immitis, Histoplasma capsulatum, Leishmania spp.

Are steady against drug: Corynebacterium spp., Pseudomonas aeruginosa, Mycobacterium tuberculosis, Treponema spp., Leptospira spp., viruses.

Colibacillus life activity oppresses that leads to reduction of synthesis of thymine, Riboflavinum, niacin, etc. group B vitamins in intestines.

Pharmacokinetics. At oral administration absorption — 90%. Time of achievement of the maximum concentration in a blood plasma (Tcmax) — 1-4 h, the therapeutic level of concentration remains 7 h after a single dose. It is well distributed in an organism. Gets into breast milk, through a blood-brain and placental barrier. In lungs and urine creates the concentration exceeding the content in plasma. To a lesser extent collect in a bronchial secret, vulval allocations, a secret and tissue of a prostate gland, liquid of a middle ear, cerebrospinal fluid, bile, bones, saliva, watery moisture of an eye, breast milk, intersticial liquid. Communication with proteins of plasma — 66% at sulfamethoxazole, at Trimethoprimum — 45%.

Sulfamethoxazole with formation of acetylized derivatives is more metabolized. Metabolites have no antimicrobic activity.

It is removed by kidneys in the form of metabolites (80% during 72 h) and in not changed look (20% of sulfamethoxazole, 50% of Trimethoprimum); insignificant quantity — through intestines. The elimination half-life (T1/2) of sulfamethoxazole — 9-11 h, Trimethoprimum — 10-12 h, at children — significantly less also depends on age: till first year — 7-8 h, 1-10 years — 5-6 h. At elderly and patients with a renal failure of T1/2 increases.

Indications to use:

Infections of urinogenital bodies: urethritis, cystitis, pyelitis, pyelonephritis, prostatitis, epididymite, gonorrhea (men's and women's), venereal ulcer, venereal lymphogranuloma, inguinal granuloma; respiratory infections: bronchitis (acute and chronic), bronchoectatic disease, lung fever, bronchial pneumonia, pleura empyema, lung abscess; infections of ENT organs: average otitis, sinusitis, laryngitis, quinsy; digestive tract infections: a typhoid, a paratyphoid, a salmonellonositelstvo, cholera, dysentery, cholecystitis, a cholangitis, the gastroenteritis caused by enterotoksichny strains E. coli; infections of skin and soft tissues: acne, furunculosis, pyoderma, abscess and wound fever; osteomyelitis (acute and chronic), a brucellosis (acute), sepsis, peritonitis, meningitis, brain abscess, osteoarticulary infections, the South American zymonematosis, malaria (Plasmodium falciparum), a toxoplasmosis and whooping cough (as a part of complex therapy), scarlet fever.

Route of administration and doses:

Drug is used inside in tablets. The dose is established individually taking into account weight of a course of an infection and sensitivity of the activator.

To adults and children 12 years are more senior appoint ^{Co-trimoksazol-Akri®} of a tablet of 0,48 g: on 2 tablets two times a day (in 12 hours). In hard cases — on 3 tablets 2 times a day. At persistent infections — on 1 tablet 2 times a day.

To children up to 12 years appoint ^{Co-trimoksazol-Akri®} of a tablet of 0,12 g. The average daily dose is defined at the rate of sulfamethoxazole of 0,03 g and Trimethoprimum of 0,006 g on 1 kg of body weight. To children aged from 2 up to 5 years usually appoint 2 tablets two times a day (in 12 hours), aged from 6 up to 12 years on 4 tablets two times a day (in 12 hours).

Course of treatment from 7 to 14 days. At persistent infections — longer depending on the course of a disease.

Features of use:

At long courses of treatment regular blood tests as there is a probability of emergence of hematologic changes are necessary (most often symptomless).

It is necessary to be careful at purpose of drug with a hepatic unsufficiency or kidneys (if the clearance of creatinine makes 15-30 ml/min., it is recommended to accept 1/2 usual doses. Extra care has to be shown at treatment of elderly patients or patients with suspicion on initial shortage of folates.

To take the patient with allergic reactions in the anamnesis with caution.
Emergence of skin rash or diarrhea of a heavy current is the indication for drug withdrawal. For prevention of a crystalluria it is recommended to support the sufficient volume of the emitted urine. The probability of toxic and allergic complications of streptocides considerably increases at decrease in filtrational function of kidneys. It is inexpedient to use also against the background of treatment the foodstuff containing paraaminobenzoic acid in large numbers — green parts of plants (a cauliflower, spinach, bean), carrots, tomatoes.

It is necessary to avoid excessive solar and ultra-violet radiation.

Co-trimoxazole can break reaction of definition of creatinine with use of an alkaline pikrinat of Jaffe (increases creatinine level on apprx. 10%).

The risk of side effects is much higher at patients with AIDS.

It is not recommended to apply at the tonsillitis and pharyngitises caused by a beta and hemolitic streptococcus of group A because of eurysynusic resistance of strains.

Pregnancy and period of a lactation. Drug should not be used during pregnancy and feeding of the child a breast as means gets through a placenta and is allocated with mother's milk.

Side effects:

From a nervous system: headache, dizziness; in some cases — aseptic meningitis, a depression, apathy, a tremor, peripheral neuritis.

From respiratory system: bronchospasm, pulmonary infiltrates.

From the alimentary system: nausea, vomiting, anorexia, diarrhea, gastritis, abdominal pains, glossitis, stomatitis, cholestasia, increase in activity of "hepatic" transaminases, hepatitis, гепатонекроз, pseudomembranous coloenteritis.

From bodies of a hemopoiesis: leukopenia, neutropenia, thrombocytopenia, agranulocytosis, megaloblastny anemia.

From an urinary system: a polyuria, intersticial nephrite, a renal failure, a crystalluria, a hamaturia, increase in content of urea, a giperkreatininemiya, a toxic nephropathy with an oliguria and an anury.

From a musculoskeletal system: arthralgia, mialgiya.

Allergic reactions: itch, photosensitization, rash, polymorphic erythema, exfoliative dermatitis, Stephens-Johnson's syndrome, Lyell's disease, allergic myocarditis, fervescence, Quincke's edema, reddening of scleras.

Others: hypoglycemia.

Interaction with other medicines:

Drug is not recommended to be accepted along with thiazide diuretics because of risk of development of thrombocytopenia (bleeding). Increases anticoagulating activity of indirect anticoagulants, action of hypoglycemic means and a methotrexate. Co-trimoxazole reduces intensity of hepatic metabolism of Phenytoinum (extends it with T1/2 for 39%) and warfarin, strengthening their effect. Pyrimethaminum in the doses exceeding 25 mg/week increases risk of development of megaloblastny anemia.

Benzocaine, Procainum, procaineamide reduce effect.

Between diuretics (tiazida, furosemide, etc.) and peroral hypoglycemic drugs (derivative sulfanylurea) on the one hand and antimicrobic streptocides - with another development of cross allergic reaction is possible.

Phenytoinum, barbiturates, p-aminosalicylic acid (PASK) strengthen manifestations of deficit of folic acid. Derivatives of salicylic acid strengthen action. Ascorbic acid, hexamethylenetetramine (etc. the medicines acidifying urine) increase risk of development of a crystalluria. Colestyraminum reduces absorption therefore it should be taken in 1 h after or for 4-6 h before co-trimoxazole reception. Reduces reliability of peroral contraception (oppresses intestinal microflora and reduces enterohepatic circulation of hormonal connections).

Rifampicin reduces Trimethoprimum elimination half-life. The combined purpose of co-trimoxazole and cyclosporine after kidney operations worsens a condition of patients.

Contraindications:

Hypersensitivity (including to streptocides), a liver and/or renal failure (clearance of creatinine less than 15 ml/min.), aplastic anemia, B12-scarce anemia, an agranulocytosis, a leukopenia, deficit glyukozo-6-fosfatdegidrogenazy, pregnancy, the lactation period, children's age up to 3 months (for oral administration), a hyperbilirubinemia at children.

With care use drug at children of early age; at deficit of folic acid, bronchial asthma, diseases of a thyroid gland. Purpose of drug demands control of a blood picture.

Overdose:

Symptoms: nausea, vomiting, intestinal colic, dizziness, headache, drowsiness, depression, syncope, confusion of consciousness, vision disorder, fever, hamaturia, crystalluria; at long overdose — thrombocytopenia, a leukopenia, megaloblastny anemia, jaundice.

Treatment: the gastric lavage, acidulation of urine increases removal of Trimethoprimum, liquid reception inside, in oil — 5-15 mg/days of calcium of a folinat (eliminates action of Trimethoprimum on marrow), if necessary — a hemodialysis.

Storage conditions:

Not to use after the term specified on packaging. List B. To store in the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 4 years.

Issue conditions:

According to the recipe

Packaging:

On 10 or 20 tablets in a blister strip packaging. On 10, 20, 50, 500 or 1000 tablets (on 500 or 1000 tablets — for a hospital) in bank of orange glass. Each can on 10, 20 or 50 tablets or 1, 2, 3, 4 or 5 blister strip packagings on 10 tablets, or on 1 or 2 blister strip packagings on 20 tablets together with the instruction on a medical use is placed in a pack from a cardboard. Each can on 500 or 1000 tablets together with the instruction on a medical use is wrapped paper wrapping or bag and placed in a transport container.