DETKIN [Co-trimoxazole] 240 mg/5 ml Oral suspension
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 5 ml
suspension contains:
active substances: cульфаметоксазол 200 мг,
триметоприм
40 мг;
excipients: xanthan gum, sodium citrate, sodium benzoate,
sucrose, strawberry essence, ethyl alcohol, purified water.
Dosage form
Suspension for oral administration.
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 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; 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 up to 3 months;
•
hypersensitivity to the
components of the drug.
Method of administration and dosage
The drug is taken during or after meals. Drinking plenty of fluids is
recommended during treatment.
The dosage regimen is individual depending on the severity of the
disease, the sensitivity and type of pathogen, and the age of the patient. For
uncomplicated infections, the following are prescribed: from 3 months to 6
months, 2-2.5 ml of suspension 2 times a day, from 6 months to 6 years, 2.5 - 5
ml of suspension 2 times a day, from 6 to 12 years, 5 -10 ml of suspension 2
times a day, over 12 years of age and adults 10-20 ml of suspension 2 times a
day Duration of treatment from 5 to 14 days. In case of prolongation of the
course of treatment for more than 5 days and/or increase in dose, hematological
monitoring is necessary; in case of changes in the blood picture, it is
necessary to prescribe folic acid 5-10 mg per day.
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.
Renal
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 pneumonia caused by P. jirovecii), as well as the following groups
of patients: patients with a history of impaired potassium metabolism,
receiving standard doses of the drug ; patients with renal failure; patients
receiving drugs that contribute to the development of hyperkalemia.
Special
groups of patients: 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. They disappear after administration of folic acid.
Due
to the possibility of hemolysis, Detkin should not be prescribed to patients
with glucose-6-phosphate dehydrogenase deficiency, except for 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 administration 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 use of 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, it is necessary to ensure sufficient fluid
intake and adequate diuresis to prevent crystalluria.
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, impaired renal
function, 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.
Metabolism: 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
sulfonamide overdose - 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
trimethoprim poisoning, 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 15°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 таблеток в блистере из алюминиевой фольги. 1 блистер вместе с инструкцией по применению в картонной коробке.