Co-trimoxazole

Co-trimoxazole – the combined antimicrobic sulfanamide drug.

Form of release and structure

• Tablets of 120 mg (on 10 pieces in packagings planimetric cell, 3 packagings in a pack cardboard; on 20 pieces in banks, 1 bank in a pack cardboard; on 10 pieces in packagings of planimetric bezjyacheykovy, 100 packagings in a box cardboard);
• Tablets of 480 mg (on 10 pieces in blisters, 1 or 2 blisters in a pack cardboard; on 10 pieces in packagings planimetric cell, 3 packagings in a pack cardboard; on 20 pieces in banks, 1 bank in a pack cardboard; on 10 pieces in packagings of planimetric bezjyacheykovy, 100 packagings in a box cardboard);
• Tablets of 960 mg (in packagings on 10, 20, 100 or 500 pieces);
• Suspension for intake (on 50, 100 or 125 mg in dark glass bottles, 1 bottle complete with a dosing spoon in a pack cardboard);
• Granules for preparation of suspension for intake (on 4,8 g in bottles of 100 ml, in packaging of 1 or 20 bottles).

Active agents as a part of drug:

• 1 tablet of 120 mg: sulfamethoxazole – 100 mg and Trimethoprimum – 20 mg;
• 1 tablet of 480 mg: sulfamethoxazole – 400 mg and Trimethoprimum – 80 mg;
• 1 tablet of 960 mg: sulfamethoxazole – 800 mg and Trimethoprimum – 160 mg;
• 5 ml of suspension: sulfamethoxazole – 200 mg and Trimethoprimum – 40 mg;
• 5 ml of the suspension prepared from granules: sulfamethoxazole – 200 mg and Trimethoprimum – 40 mg.

Indications to use

Monotherapy:

• Respiratory infections: acute and chronic bronchitis, bronchial pneumonia, lung and pneumocystic fever, bronchoectatic disease;
• Digestive tract infections: cholera, a salmonellonositelstvo, a cholangitis, dysentery, a paratyphoid, cholecystitis, a typhoid and the gastroenteritis caused by enterotoksichny strains of Escherichia coli;
• Infections of ENT organs: quinsy, laryngitis, sinusitis, scarlet fever, average otitis;
• Infections of urinogenital bodies: gonorrhea (men's and women's), inguinal granuloma, venereal lymphogranuloma, venereal ulcer, epididymite, prostatitis, pyelitis, cystitis, pyelonephritis, urethritis;
• Infections of soft tissues and skin: wound fevers, furunculosis, acne, pyoderma.

Complex therapy:

• Acute brucellosis;
• Toxoplasmosis;
• Plasmodium falciparum;
• South American zymonematosis;
• Acute and chronic osteomyelitis;
• Other osteoarticulary infections.

Contraindications

Absolute:

• Renal failure (clearance of creatinine less than 15 ml/min.);
• B12 - scarce anemia;
• Aplastic anemia;
• Liver failure;
• Deficit glyukozo-6-fosfatdegidrogenazy;
• Agranulocytosis, leukopenia;
• Hyperbilirubinemia at children;
• Children's age up to 3 months;
• Pregnancy and lactation;
• Hypersensitivity to drug or other streptocides.

Relative:

• Bronchial asthma;
• Deficit of folic acid;
• Diseases of a thyroid gland;
• Renal failure and liver;
• Allergic reactions in the anamnesis.

Route of administration and dosage

Co-trimoxazole should be accepted inside in time or after food.

From granules prepare suspension. For this purpose add 100 ml of boiled water to a bottle and carefully mix.

The recommended drug doses in the form of tablets:

• Adults and children are more senior than 12 years: 960 mg are 1 times/days old or on 480 mg 2 times/days, in hard cases – on 480 mg 3 times/days, at persistent infections – on 480 mg 2 times/days;
• Children of 6-12 years: on 240-480 mg 2 times/days;
• Children of 2-6 years: on 120-240 mg 2 times/days;
• Children of 1-2 years: on 120 mg 2 times/days.

The recommended drug doses in the form of the suspension including prepared from granules:

• Adults and teenagers are more senior than 12 years: on 960 mg 2 times/days;
• Children of 7-12 years: on 480 mg 2 times/days;
• Children of 4-6 years: on 240-480 mg 2 times/days;
• Children from 7 months to 6 years: on 120-240 mg 2 times/days;
• Children of 3-6 months: on 120 mg 2 times/days.

Duration of treatment depends on the indication and the overall clinical picture, usually makes from 5 to 10 days. After clinical symptoms of a disease disappear, administration of drug should be continued within 2 days. Therapy of an acute brucellosis lasts 3-4 weeks, a paratyphoid and a typhoid – 1-3 months. Treatment of persistent infections longer.

For prevention of a recurrence of persistent infections of an urinary system Co-trimoxazole is appointed to adults and teenagers 12 years on 480 mg of 1 times a day for the night, to children up to 12 years – on 12 mg/kg/days are more senior. The course can last from 3 to 12 months.

At acute cystitis at children at the age of 7-16 years appoint 480 mg 2 times/days within 3 days.

The recommended dose at the pneumonia caused by Pneumocystis carinii makes 120 mg/kg/days in stages bucketed 6 hours for 14 days.

The initial dose at typhus makes 3 times/days on 960 mg, after heat falling off the dose is reduced to 960 mg by 2 times/days, treatment is continued within at least 2 weeks. To children the dose is reduced twice.

To patients with gonorrheal pharyngitis Co-trimoxazole is appointed in case of hypersensitivity to penicillin: in a dose of 4320 mg once in days within 5 days.

At some diseases at adults the doctor can recommend a single dose of drug or carrying out short-term courses. For example:

• Uncomplicated cystitis at women: 2400 mg once with a large amount of water;
• Shankroid: 3840 mg once with a large amount of water;
• Uncomplicated acute gonorrhea: 2400 mg once, 8 hours later – reception of a similar dose.

More than 25 ml/minute dose adjustment is not required to patients with a renal failure at the clearance of creatinine (CC), at KK from 15 to 25 ml/minute appoint a standard dose during the first 3 days of therapy, further – on ½ standard doses. Patients with KK less than 15 ml/minute can apply ½ standard doses only provided that the patient passes a hemodialysis.

Side effects

• From bodies of a hemopoiesis: agranulocytosis, thrombocytopenia, megaloblastny anemia, neutropenia, leukopenia;
• From a nervous system: вертиго, headache; in some cases – a tremor, apathy, peripheral neuritis, a depression, aseptic meningitis;
• From respiratory system: pulmonary infiltrates, bronchospasm;
• From the alimentary system: stomatitis, glossitis, gastritis, diarrhea, abdominal pain, loss of appetite, cholestasia, nausea, vomiting, increase in activity of hepatic transaminases, pseudomembranous coloenteritis, гепатонекроз, hepatitis;
• From an urinary system: a hamaturia, a crystalluria, a giperkreatininemiya, a polyuria, increase in concentration of urea, a renal failure, intersticial nephrite, a toxic nephropathy with an oliguria and an anury;
• From a musculoskeletal system: mialgiya, arthralgia;
• Allergic reactions: rash, itch, exfoliative dermatitis, hyperemia of scleras, Quincke's disease, fervescence, allergic myocarditis, photosensitization, toxic epidermal necrolysis, multiformny exudative erythema;
• Others: hypoglycemia.

Special instructions

At prolonged treatment (more than 1 month) it is regularly necessary to do blood test since there is a risk of emergence of hematologic changes (including symptomless). These changes can be reversible thanks to reception of folic acid (in a daily dose of 3-6 mg), at the same time antimicrobic activity of drug significantly is not broken. Extra care should be observed at treatment of elderly people and patients with suspicion on initial shortage of folates. Additional purpose of folic acid is also reasonable at prolonged treatment by Co-trimoxazole in high doses. Besides, at prolonged treatment it is necessary to watch a functional condition of a liver and kidneys.

In order to avoid development of a crystalluria it is necessary to provide adequate water loading and to support the sufficient volume of the emitted urine. At decrease in filtrational function of kidneys the risk of development of allergic and toxic complications of streptocides considerably increases.

During treatment it is recommended to avoid excessive solar and ultra-violet radiation, and also to exclude from a diet products which contain in large numbers paraaminobenzoic acid (PABK), such as tomatoes, carrots, green parts of plants (spinach, a cauliflower and bean).

At patients with a syndrome of the acquired immune deficit (AIDS) the risk of development of side effects is much higher.

Because of eurysynusic resistance of strains it is not recommended to appoint Co-trimoxazole at the pharyngitises and tonsillitis caused by a beta and hemolitic streptococcus of group A.

Medicinal interaction

• Derivatives of salicylic acid: effect of Co-trimoxazole amplifies;
• Methotrexate: its toxicity increases;
• Hypoglycemic drugs: their action amplifies;
• Indirect anticoagulants: their activity increases;
• Phenytoinum, warfarin: intensity of their hepatic metabolism decreases, effects amplify;
• Oral contraceptives: their efficiency decreases;
• Procainum, benzocaine, procaineamide and other medicines as a result of which hydrolysis PABK is formed: reduce effect of Co-trimoxazole;
• Rifampicin: Trimethoprimum elimination half-life is reduced;
• Pyrimethaminum in doses more than 25 mg/week: the risk of development of megaloblastny anemia increases;
• Diuretics (especially tiazida): the risk of development of thrombocytopenia, especially at elderly people increases;
• P-aminosalicylic acid, Phenytoinum, barbiturates: manifestations of deficit of folic acid amplify;
• Colestyraminum: Co-trimoxazole absorption decreases (in this regard drug should be accepted through in 1 hour prior to or in 4-6 hours after reception of Colestyraminum);
• The drugs oppressing a marrowy hemopoiesis: the risk of a miyelosupressiya increases;
• Indometacin, Butadionum, Naproxenum, salicylates and some other non-steroidal anti-inflammatory drugs: strengthening of effect of Co-trimoxazole with development of undesirable effects is possible;
• Chloridinum: antimicrobic effect of drug amplifies.

Between diuretics (furosemide, tiazida, etc.) and peroral hypoglycemic drugs (sulphonylurea derivatives), on the one hand, and antimicrobic streptocides, on the other hand, development of cross allergic reaction is possible.

Terms and storage conditions

To store in dry, protected from light and the place, unavailable to children. Tablets and granules – at a temperature of 15-25 ºС, suspension – at a temperature up to 15 ºС.

Period of validity of tablets – 5 years, suspension and granules – 2 years. The suspension prepared from granules can be stored within 2 weeks at the room temperature, up to 4 weeks – in the refrigerator.