DETKIN [Co-trimoxazole] 480 mg Tablets
instructions for the medical use of
the medicinal product
DETKIN
Tradename
Detkin, Деткин
International non-proprietary name
or generic name
Co-trimoxazole
(sulfamethoxazole+trimethoprim),
Ко-тримоксазол (cульфаметоксазол+триметоприм)
Composition
Each tablet
contains:
active ingredients: sulfamethoxazole 400 mg, trimethoprim 80 mg;
excipients: starch, dextrin, microcrystalline cellulose,
hypromellose, talc, magnesium stearate.
Dosage form
Tablets.
Pharmacotherapeutic group
Combined antimicrobial agent.
ATX code – J01EE01
Pharmacological
properties
Pharmacodynamics
A combined antibacterial drug
containing sulfamethoxazole and trimethoprim.
Sulfamethoxazole,
similar in structure to para-aminobenzoic acid (PABA), disrupts the synthesis
of dihydrofolic acid in bacterial cells, preventing the inclusion of PABA in
its molecule.
Trimethoprim
enhances the effect of sulfamethoxazole by interfering with the reduction of
dihydrofolic acid into tetrahydrofolic acid, the active form of folic acid
responsible for protein metabolism and microbial cell division.
It is a broad-spectrum
bactericidal drug.
Active
against the following microorganisms: Streptococcus spp. (hemolytic strains are
more sensitive 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 spp.,
Enterobacter spp., Legionella pneumopbila, Providencia, some Pseudomonas
species (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; Actinomyces israelii; pathogenic fungi - 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
thiamine, riboflavin, nicotinic acid and other B vitamins in the intestines.
The
duration of therapeutic action is 7 hours.
Pharmacokinetics
Suction
After
taking the drug orally, the active substances are completely absorbed from the
gastrointestinal tract. Cmax in blood plasma is achieved within 1-4 hours after
oral administration.
Distribution
Trimethoprim
penetrates well into the tissues and biological environments of the body:
lungs, kidneys, prostate, bile, saliva, sputum, cerebrospinal fluid. The
binding of trimethoprim to plasma proteins is 50%; sulfamethoxazole - 66%.
Removal
T1/2
of trimethoprim - 8.6-17 hours, sulfamethoxazole - 9-11 hours. The main route
of elimination is the kidneys; in this case, trimethoprim is excreted unchanged
up to 50%; sulfamethoxazole - 15-30% in active form.
Indications for use
Treatment of infectious and
inflammatory diseases caused by microorganisms sensitive to the drug:
• respiratory tract infections
(including bronchitis, pneumonia, lung abscess, pleural empyema);
• otitis media, sinusitis;
• infections of the
genitourinary system (including pyelonephritis, urethritis, salpingitis,
prostatitis);
• gastrointestinal infections
(including typhoid fever, paratyphoid fever, bacterial dysentery, cholera,
diarrhea);
• infections of the skin and
soft tissues (including furunculosis, pyoderma).
• infections caused by a
number of microorganisms (combination with other antibiotics is possible), for
example: brucellosis, acute and chronic osteomyelitis, nocardiosis,
actinomycosis, toxoplasmosis.
Contraindications
• established diagnosis of liver parenchyma damage;
• severe renal dysfunction in the absence of the ability to control the
concentration of the drug in the blood plasma;
• severe renal failure (creatinine clearance less than 15 ml/min);
• severe blood diseases (aplastic anemia, B12-deficiency anemia,
agranulocytosis, leukopenia, megaloblastic anemia, anemia, hyperbilirubinemia
in children associated with folic acid deficiency);
• deficiency of glucose-6-phosphate dehydrogenase (risk of hemolysis);
• pregnancy;
• lactation;
• children under 3 years of age;
• hypersensitivity to the components of the drug.
Method of administration and dosage
The drug is taken
orally after meals with a sufficient amount of liquid. The dose is set
individually.
For children aged 3 to 5 years, the drug is prescribed 240 mg 2 times a day; children aged 6 to 12 years - 480 mg 2
times a day.
For pneumonia, the drug is prescribed at the
rate of 100 mg of sulfamethoxazole per 1 kg of body weight/day. The interval
between doses is 6 hours, duration of use is 14 days.
For adults and children over 12 years of age, the drug is prescribed 960 mg 2 times/day, for
long-term therapy - 480 mg 2 times/day.
The duration of
treatment is from 5 to 14 days.
When the course
of therapy lasts more than 5 days and/or the dose of the drug is increased, it
is necessary to monitor the peripheral blood picture; if pathological changes
occur, folic acid should be prescribed at a dose of 5-10 mg/day.
In patients with renal failure with CC 15-30 ml/min, the standard dose of the drug should be reduced by
50%.
Special instructions and precautions
Before
using the drug, consult your doctor.
The
drug should be prescribed only in cases where the advantage of such combination
therapy over other antibacterial single drugs outweighs the possible risk.
Because the sensitivity of bacteria to antibacterial drugs in vitro varies
across different geographic areas and over time, local patterns of bacterial
susceptibility should be taken into account when selecting a drug.
Hypersensitivity and allergic reactions
At
the first appearance of skin rash or any other severe adverse reaction, the
drug should be discontinued. Patients with a tendency to allergic reactions and
bronchial asthma should prescribe Detkin with caution.
Infiltrates
in the lungs (like eosinophilic or allergic alveolitis) can manifest themselves
with symptoms such as cough or shortness of breath. If these symptoms appear or
suddenly increase, it is necessary to re-examine the patient and consider
stopping treatment with Detkin.
Kidney disorders
Sulfonamides,
including Detkin, may increase diuresis, especially in patients with edema
caused by heart failure. Careful monitoring of renal function and potassium
concentration in the blood serum is necessary for patients receiving high doses
of the drug (including during treatment of Pneumocystis jirovecii pneumonia),
as well as the following groups of patients: patients with a history of
impaired potassium metabolism receiving standard doses drug; patients with
renal failure; patients receiving drugs that contribute to the development of
hyperkalemia.
Special patient groups
In
elderly and senile patients, as well as in patients with concomitant diseases,
for example, impaired renal and/or liver function, or while taking other drugs,
there is an increased risk of severe adverse reactions; in these cases, the
risk of development is related to the dose and duration of therapy.
The
duration of treatment with Detkin should be as short as possible, especially in
elderly and senile patients. If renal function is impaired, the dose should be adjusted.
Patients with severe renal impairment (creatinine clearance 15-30 ml/min)
receiving trimethoprim-sulfamethoxazole should be carefully monitored for the
development of toxicity symptoms (nausea, vomiting, hyperkalemia).
For
patients with severe hematological diseases, Detkin can be prescribed only as
an exception.
In
elderly and senile patients, as well as in patients with pre-existing folic
acid deficiency or renal failure, hematological changes characteristic of folic
acid deficiency may occur. These changes disappear after administration of
folic acid.
Due
to the possibility of hemolysis, the drug should not be prescribed to patients
with glucose-6-phosphate dehydrogenase deficiency, except in the presence of
absolute indications and only in minimal doses.
As
with any sulfonamides, caution should be exercised in patients with porphyria
or thyroid dysfunction. Patients whose metabolism is characterized by “slow
acetylation” are more likely to develop idiosyncrasy to sulfonamides.
Long-term therapy
With
long-term use of the drug Detkin, it is necessary to regularly determine the
number of blood cells. If there is a significant decrease in the number of any
blood cells, the drug should be discontinued.
Patients
receiving long-term treatment with Detkin (especially with renal failure)
should regularly undergo a general urine test and monitor kidney function.
During treatment, sufficient fluid intake and adequate diuresis should be
ensured to prevent crystalluria.
Impact on laboratory results
Trimethoprim
may change the results of determining the level of methotrexate in serum,
carried out by the enzymatic method, but does not affect the result when
choosing a radioimmunological method.
Co-trimoxazole
can increase the results of the Jaffe reaction with picric acid for the
quantitative determination of creatinine by 10%.
Influence
on the ability to drive vehicles and mechanisms
The drug may
cause undesirable symptoms such as headache, tremor, nervousness, and fatigue;
caution should be exercised when driving or servicing machinery.
Interaction with
other medicinal products
When using the drug
simultaneously with thiazide diuretics, there is a risk of developing
thrombocytopenia and bleeding (the combination is not recommended).
Co-trimoxazole increases the
anticoagulant activity of indirect anticoagulants, as well as the effect of
hypoglycemic drugs and methotrexate.
Co-trimoxazole reduces the
intensity of hepatic metabolism of phenytoin (increases its T1/2 by 39%) and
warfarin, enhancing their effect.
Rifampicin reduces T1/2 of
trimethoprim.
With simultaneous use of
pyrimethamine, the risk of developing megaloblastic anemia increases.
With the simultaneous use of
diuretics (usually thiazide), the risk of developing thrombocytopenia
increases.
Benzocaine, procaine,
procainamide (as well as other drugs, as a result of the hydrolysis of which
PABA is formed) reduce the effectiveness of Detkin.
Between diuretics (including
thiazides, furosemide) and oral hypoglycemic agents (sulfonylurea derivatives),
on the one hand, and antibacterial agents of the sulfonamide group, on the
other hand, the development of a cross-allergic reaction is possible.
Phenytoin, barbiturates,
para-aminosalicylic acid increase the manifestations of folic acid deficiency
when used simultaneously with Detkin.
Salicylic acid derivatives
enhance the effect of the drug.
Ascorbic acid,
hexamethylenetetramine (as well as other drugs that acidify urine) increase the
risk of developing crystalluria during the use of Detkin.
Cholestyramine reduces
absorption when taken concomitantly with other drugs, so it should be taken 1
hour after or 4-6 hours before taking co-trimoxazole.
When used simultaneously with
drugs that inhibit bone marrow hematopoiesis, the risk of developing
myelosuppression increases.
Detkin may increase plasma
concentrations of digoxin in some elderly patients and may reduce the
effectiveness of tricyclic antidepressants.
Concomitant use with
dofetilide, paclitaxel, amiodarone and clozapine is contraindicated.
In patients after kidney
transplantation, with the simultaneous use of co-trimoxazole and cyclosporine,
a transient dysfunction of the transplanted kidney is observed, manifested by
an increase in serum creatinine concentrations, which is probably caused by the
effect of trimethoprim.
Side effect
From the nervous
system: headache, dizziness; in some cases - aseptic meningitis, depression,
apathy, tremor, peripheral neuritis.
From the
respiratory system: bronchospasm, suffocation, cough, pulmonary infiltrates.
From the
digestive system: nausea, vomiting, loss of appetite, diarrhea, gastritis, abdominal
pain, glossitis, stomatitis, cholestasis, increased activity of liver
transaminases, hepatitis, sometimes with cholestatic jaundice, hepatonecrosis,
pseudomembranous enterocolitis, pancreatitis.
From the
hematopoietic system: leukopenia, neutropenia, thrombocytopenia, agranulocytosis,
megaloblastic anemia, aplastic and hemolytic anemia, eosinophilia,
hypoprothrombinemia, methemoglobinemia.
From the urinary
system: polyuria, interstitial nephritis, renal dysfunction, crystalluria,
hematuria, increased urea concentration, hypercreatininemia, toxic nephropathy
with oliguria and anuria.
From the
musculoskeletal system: arthralgia, myalgia.
Allergic
reactions: itching, photosensitivity, urticaria, drug fever, rash, exudative
erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal
necrolysis (Lyell's syndrome), exfoliative dermatitis, allergic myocarditis,
fever, angioedema, scleral hyperemia.
Metabolic: hypoglycemia, hyperkalemia,
hyponatremia.
If any of the
side effects indicated in the instructions get worse, or you notice any other
side effects not listed in the instructions, tell your doctor.
Symptoms: in case of an overdose of sulfonamide - lack of
appetite, intestinal colic, nausea, vomiting, dizziness, headache, drowsiness,
loss of consciousness, fever, hematuria, crystalluria are also possible. Bone
marrow suppression and jaundice may develop later.
After
acute poisoning with trimethoprim, nausea, vomiting, dizziness, headache,
depression, disturbance of consciousness, and suppression of bone marrow
function are possible.
It
is not known what dose of co-trimoxazole can be life-threatening.
Chronic
poisoning: Use of co-trimoxazole in high doses over a long period can lead to
suppression of bone marrow function, manifested by thrombocytopenia, leukopenia
or megaloblastic anemia.
Treatment: discontinuation of the drug and taking measures
aimed at removing it from the gastrointestinal tract (carry out gastric lavage
no later than 2 hours after taking the drug or induce vomiting), drinking
plenty of fluids if diuresis is insufficient and renal function is preserved.
Administer calcium folinate (5-10 mg/day). Acidic urine accelerates the
elimination of trimethoprim, but may also increase the risk of sulfonamide
crystallization in the kidneys.
The
blood picture, the composition of plasma electrolytes and other biochemical
parameters should be monitored. Hemodialysis is moderately effective, but
peritoneal dialysis is ineffective.
Storage conditions
Store at a temperature not exceeding 25°C.
Keep out of the reach of children!
Shelf life
3 years. Do not use after the expiry date stated on
the packaging.
Vacation conditions
Dispensed by prescription.
Release form
10 tablets in an aluminum foil blister. 1 blister along with instructions for use in a cardboard box.