Biseptol 480 Adamed medicine for infections caused by sensitive microorganisms (1 blister x 20 tablets)

Pharmacokology

Pharmacological group: combining sulfamid and trimethoprim.

ATC code: J01EE01.

Mechanism of action

sulfamethoxazol inhibits the use of para-aminobenzoic acid in the synthesis of dihydrofolate of bacterial cells, resulting in bacteria. Trimethoprim inhibits reversible enzyme dihydrofolat reductase (DHFR) of bacteria, is an enzyme that activates folate transforming pathway from moving to Tetrahydrofolate. As a result, Trimethoprim has a bactericidal effect. Trimethoprim and sulfamethoxazol inhibit the next 2 stages in the biosynthesis of the essential purin and nucleic acids of many bacteria.

trimethoprim is associated with serum DHFR but much inferior to bacteria. The affinity of the drug with DHTR in mammals is about 500,000 times lower than bacteria.

Medicinal resistance mechanism

In vitro studies show that bacterial resistance may grow slower if used in combination with sulfamethoxazol and trimethoprim compared to using antibiotic monopoly.

resistance to sulfamethoxazol can occur by different mechanisms. Mutations may increase the concentration of PABA, compete with sulfamethoxazol results that reduce the effect of inhibiting the enzyme dihydropteroat synthetase. Another mechanism is that through plasmid intermediaries, thereby changing the enzyme dihydropteroat synthetase, the affinity of this enzyme with sulfamethoxazol decreases compared to the original enzyme.

Trimethoprim resistance can occur through Plasmid intermediate mutations that change the enzyme dihydrofolate reductase, the affinity of this enzyme with trimethoprim decreases compared to the original enzyme.

trimethoprim is associated with plasma DHFR but much lower than in bacteria. The affinity for DHFR in mammals is about 50 000 times lower than in bacteria.

Many species of sensitive bacteria in vitro with trimethoprim and sulfamethoxazol are lower than concentrations than the concentration of drugs in blood, tissue, urine after the recommended dose. Like other antibiotics, in vitro activity does not mean clinical activity.

Sensitive fractures

Sensitive fractures for typical pathogenic bacteria:

eucast:

trimethoprim: sulfamethoxazol ratio 1:19. Sensitive fractures represent trimethoprim concentration.

antibacterial spectrum

The resistance may vary depending on geography and over time for the selected bacteria strains and local information about drug resistance is necessary, especially for severe bacterial bacteria. When needed, consult experts if suspected.

This information only gives instructions close to the probability of bacteria can be sensitive to antibiotics.

trimethoprim/sulfamethoxazol works on the following bacteria:

Table 1: Antibacterial spectrum of trimethoprim/sulfamethoxazol Bacteria

Staphylococcus saprophyticus

streptococcus pyogenes

Haemophilus Influenzae

klebsiella oxytoca

Moraxella Catrhalis

salmonella spp.

stenotrophomonas maltophilia

Yersinia spp.

Enterococcus fast

Nocardia spp.

Staphylococcus epidermidis

streptococcus pneumoniae

Gram -negative aerobic microorganisms:

Enerobacter aerogenes

Escherichia Coli

klebsiella pneumoniae *

klebsiella pneumonia

proteus mirabilis

proteus vulgaris

Providencia spp.

Serratia Marcescens

Shigella spp.

Vibrio Cholerae After taking the medicine, Trimethoprim and Sulfamethoxazol absorb quickly and almost completely. The presence of food does not affect the absorption of the drug. The absorption peak is reached from 14 hours after taking the drug, related to the dose and maintain the dose level for 24 hours. The stable concentration of the drug in adults is achieved after 2-3 days of taking the drug. Both antibiotic components do not significantly affect the concentration of the remaining serum.

distribution

approximately 50% trimethoprim links to serum protein. Trimethoprim concentration in tissue is higher than the concentration of drugs in serum, lungs, and kidneys. Trimethoprim concentration in bile fluid, prostate, saliva, sputum and vaginal discharge is higher in serum. Trimethoprim concentration in breast milk, cerebrospinal fluid, middle ear, joint fluid and endothelial fluid is sufficient to work. Trimethoprim passes through the amniotic fluid and into the placenta, achieving the concentration of drugs close to the concentration of the drug in the mother serum.

approximately 66% sulfamethoxazol linked to serum protein. Sulfamethoxazol concentration is active in amniotic fluid, bile, cerebrospinal fluid, middle ear fluid, joint fluid, phlegm and endothelial fluid ranging from 20 to 50% of serum concentration.

Biological metabolism

sulfamethoxazol is excreted intact through the kidneys about 15-30% of the dose. Sulfamethoxazol is more powerful than trimethoprim through acetylation, oxidation and glucuronid. In about 72 hours, nearly 85% of the drug is excreted through the kidneys in the form of non-metabolic with its main metabolites (N4-acetylated).

excretion

Trimethoprim's semi -exhaust time in adults Normal kidney function is about 8.6 to 17 hours. This time increases according to the coefficient of 1.5 to 3 when the creatinine clearance is less than 10 ml/min. There is no significant difference between the group of older patients and a group of young patients. Trimethoprim is excreted mainly through the kidneys and is approximately 50% of the dosage eliminated in the form of unchanged within 24 hours. Some metabolites have been found in urine.

Salfamethoxazol's exhaust time in adult adults normal kidney function is about 9 to 11 hours.

There is no change in the semi -waste time of sulfamethoxazol for cases of renal function but there is a prolonged sale time of its main metabolites such as acetylate metabolites when creatinine clearance is below 25 ml/min.

sulfamethoxazol excreted mainly through the kidneys, about 15% to 30% found in urine in activity. Pharmacokinetics in children with normal kidney function show that both trimethoprim and sulfamethoxazol depend on age. The elimination of trimethoprim/sulfamethoxazole decreases in newborns, in the first 2 months of life, then even trimethoprim sulfamethoxazol shows higher excretion with higher clearance and shorter selling time. The most prominent difference in infants (31.7 months to 24 months) and gradually decreases with age, when compared to children (1 year to 3.6 years old), children (7.5 years old to In the elderly patients, there is a reduction in the kidneys of sulfamethoxazol.

Special patient group:

Patients with renal failureTrimethoprim's semi -exhaust time increases with a factor of 1.5 to 3 when creatinine clearance is less than 10 ml/min. When creatinine clearance is lowered below 30 ml/min, the dose of co-trimoxazol should be reduced.

Patients with liver failure

Be cautious when used with patients with severe liver parenchyma lesions because there are many changes in the absorption and biological metabolism of trimethoprim and sulfamethoxazole.

Elderly patients

There is a slight reduction in the kidney clearance of sulfamethoxazol but have not been observed in trimethoprim.

in children

See in the dose.

Nocardia disease - Adults (> 18 years old):

No consensus for the most appropriate dose. Dosage for adults from 480mg trimethoprim/ 2400mg sulfamethoxazol to 640mg trimethoprim/ 3200mg sulfamethoxazol per day for up to 3 months is used.

Toxoplasma disease:

There is no most suitable dose consensus for treatment or prophylaxis for this infection. The decision should be based on clinical experience. For prophylaxis, the recommended dose for prophylactic pneumonia caused by Pneumocystis Jiroveci may be suitable.

Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.What to do when overdose?

Symptoms:

Nausea, vomiting, dizziness, restlessness may be overdose symptoms. Bone marrow failure has been reported in the overdose of acute Trimethoprim.

Treatment:

Causes vomiting, gastric lavage. Depending on the kidney function, recommend the use of transmission if the urine is low. Both trimethoprim and sulfamethoxazol are separated by hemorrhage. Peritoneal jurisdiction is not effective.

What to do when you forget 1 dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double doses to compensate for missed dose.

Be cautious when using

need to be very careful when taking the drug for patients in the following cases:

Death cases, although very rare, occurred due to serious reactions including Stevens-Johnson syndrome, poisoned epidermal necrosis, acute liver necrosis, granulocytosis, anemia, other blood disorders and the sensitivity of the respiratory tract.

Skin reactions threatening the life of Stevens-Johnson syndrome (SJS) and poisoned epidermal necrosis (Ten) have been reported when using cotrimoxazol.

Patients should be notified of signs and symptoms and closely monitor the skin reactions. The highest risk of SJS or ten is in the first weeks of treatment.

If the patient appears symptoms or signs of sjs or ten when using co-trimoxazole, should stop taking this medication.

Good management SJS and Ten comes from early diagnosis and immediately stop using suspected drugs. Stop taking early drugs is more related to better prognosis.

If the patient appears SJS or ten when using Co-Trimoxazole, do not allow the patient to reuse Co-Trimoxazole at any time.

When starting to treat, the appearance of the whole body fever with pustules, should suspect the acute pustules syndrome (AGEP), should stop taking the drug and contraindicated use of co-trimoxazole alone or in combination with other drugs.

Special care is always encouraged when treating the elderly, because the elderly is more likely to experience adverse reactions and are more likely to suffer more serious effects, especially as a result of complex conditions, such as kidney failure and / or liver failure and / or simultaneous use of other drugs.

For patients with renal impairment should use special monitoring measures.

Should maintain the full amount of urine at all times. There is evidence of Vivo rare crystal, although Sulphonamide crystals have been recorded in urine cooled in patients taking drugs. In malnourished patients with risk of increased risk.

It is advisable to test for a monthly blood formula when taking the drug for a long time or for a folate deficiency or an elderly; Due to the possibility of disadvantaged changes in hematological test indicators due to lack of folate. Folinic acid supplements may be considered during treatment but should be cautious because it can affect antibacterial effect.

In patients with glucose-6-phosphate dehydrogenase (G-6-PD) can occur.

Co-Trimoxazole should be cautious for patients with severe allergies or bronchial asthma.

Co-Trimoxazole should not be used in the treatment of streptococci bacterial sore throats beta-haemolytic group A; Due to less efficiency than penicillin.

Trimethoprim has been recorded as a reduction in phenylalanine metabolism but does not make sense in patients with diet phenylketon, which is having a suitable diet.

Should avoid using co-trimoxazole for patients who have or suspect are at risk of Porphyria. Both trimethoprim and sulphonamide can seriously cause porphyria.

Need to closely monitor serum potassium in patients at risk of hyperkalemia and hypoglycry hypoglycemia.

Co-Trimoxazole is associated with metabolic acidosis when other potential causes have been excluded. Closely monitor when suspected metabolic acidosis.

Unless carefully monitored, co-trimoxazole should not be used for patients with serious hematological disorders. Co-Trimoxazole has been used for patients with little chemotherapy or no side effects on the bone marrow or peripheral blood.

A combination of antibiotics with co-trimoxazole should only be used when according to a doctor's assessment, the benefits of treatment are greater than any risk may occur; Should consider the use of an effective antibacterial agent.

The effect of the drug on driving and operating machinery

No research has assessed the impact of the drug on the ability to drive and operate machinery. Such adverse impacts cannot be predicted from the pharmacology of the drug. However, the patient's clinical status should be noted and the adverse impact records of the drug when considering the patient's ability to operate machinery.

Use drugs for women during pregnancy and lactation

Used in pregnant women:

trimethoprim and sulfamethoxazol through the placenta and the safety of drugs in pregnant women have not been established. Controlled studies have shown that there may be associations between exposure and folate antagonists and birth defects in humans.

Trimethoprim is a folate antagonist and, in animal studies, both active ingredients have been shown to be the cause of fetal defects.

Co-Trimoxazole should not be used during pregnancy, especially in the first three months, unless really necessary. Folate supplements should be considered if Co-Trimoxazole is used during pregnancy. Sulfamethoxazole competes with bilirubin to link with plasma albumin. When Co-Trimoxazole is used for mothers near the time of birth, the drug may remain significant in babies, causing a serious risk of increasing blood bilirubin in infants. This theoretical risk is particularly related in newborns to increase blood bilirubin, such as premature babies and babies with glucose-6-phosphate dehydrogenase deficiency.

Use drugs in breastfeeding women:

The ingredients of the drug (trimethoprim and sulfamethoxazole are excreted through breast milk. Co-trimoxazole should be avoided during the end of pregnancy and in mothers who are breastfeeding, especially when the mother or newborn is suffering from or has the risk of increased blood bilirubin. In addition, avoid using co-trimoxazole in young children for less than eight weeks due to the risk of increased blood bilirubin.

Drug interaction

Interact with laboratory tests:

Trimethoprim may hinder serum/ plasma creatinine measurement when using alkaline picrate reactions. This can lead to increased serum/ plasma creatinine results at 10%. Creatinine clearance decreases: The results of the removal measurement can be reduced from 23% to 9% while the filtration process of the glomeruli remains unchanged.

Zidovudine: In some cases of simultaneous treatment with zidovudine may increase the risk of adverse bloodstream reactions. If combined treatment is necessary, need to monitor hematology indicators.

Cyclosporin: Cotrimoxazol used with cyclosporin can be toxic to the kidneys in the kidney transplant but can recover.

Rifampicin: simultaneously use Rifampicin and Co-Trimoxazole, reducing the half-life of trimethoprim plasma after about a week of treatment. This does not have many clinical meanings.

When Trimethoprim is simultaneously used with cation drugs in the physiological pH, and is partly excreted due to the active excretion in the kidneys (for example: Procainamide, Amantadine), has the ability to inhibit excretion competition and lead to an increase in plasma or both drugs.

Diuretics (Thiazide): In the elderly patients and use diuretics, mainly Thiazide, there is a risk of thrombocytopenia with or without hemorrhage.

pyrimethamine: Co-trimoxazol is simultaneously used with pyrimethamine above 25 mg/week, increasing the risk of huge red blood cell anemia.

warfarin: Co-trimoxazole has been shown to enhance Warfarin's anticoagulant activity through inhibition of metabolic processes. Sulfamethoxazole can replace warfarin from positions attached to plasma proteins in test tubes. Should strictly control anticoagulant therapy while treatment with co-trimoxazole.

phenytoin: Co-trimoxazole extends phenytoin's disposal time and if used simultaneously can lead to phenytoin. Need to closely monitor patient condition and serum phenytoin concentration.

Digoxin: Concomitant use of trimethoprim with digoxin has been shown to increase the concentration of digoxin in plasma in elderly patients.

methotrexate: Co-trimoxazole may increase methotrexate levels in plasma. If Co-Trimoxazole is required to use in patients who are taking other antacidic drugs such as methotrexate, folate should be added. Trimethoprim affects serum methotrexate test when dihydrofolate reductase from lactobacillus casei is used in the test. No effect if methotrexate is measured by radioimmuno test.

lamivudine: Use trimethoprim/sulfamethoxazole 160mg/800mg (co-trimoxazole) increases 40% lamivudine exposure due to the effect of trimethoprim. Lamivudine does not affect the pharmacokinetics of trimethoprim or sulfamethoxazole.

Interaction with sulphonylurea hypoglycemic drugs:

Not common but have been reported.

Hemorrhage hyperpass: Be cautious in patients who use any other drugs that can cause hyperkalemia, such as enzyme inhibitors, angiotensin receptor inhibitors and potassium -keeping diuretics such as spironolactone. Simultaneous use of trimethoprim-sulfamethoxazole (co-trimoxazole) can lead to clinical hyperkalemia.

Repaglinide: Trimethoprim may increase the effect of repaglinide that can lead to hypoglycemia.

Folinic acid: Folinic acid supplementation has been shown to reduce the antibacterial effect of trimethoprim-sulfamethoxazole.This effect is observed in prophylaxis and treatment of pneumocystis jiroveci pneumonia.

contraceptive: Antibiotics may lose the effect of birth control pills. The mechanism of this effect has not been clarified. Women who are treating antibiotics should choose another contraception.

Azathioprine: There are clinical reports on opposition interaction between azathioprine and trimethoprim-sulfamethoxazole, leading to serious hematological abnormalities.