PMS-Cotrim 960mg Imexpharm Treatment Treatment (10 blisters x 10 tablets)

ATC code: J01EE01.

Mechanism of action:

Sulfamethoxazol inhibits competition in the use of para-aminobenzoic acid during the synthesis of dihydrofolate produced by bacterial cells. Trimethoprim inhibits reversible enzyme dihydrofolat reductase (DHFR), is an enzyme that operates in the conversion of folat through the path of moving dihydrofolate into tetrahydrofolate.

Depending on the conditions of influence, it may have bactericidal effects. Therefore, trimethoprim and sulfamethoxazol blocked two consecutive steps in the synthesis of purin and nucleic acid necessary for many bacteria. This coordination mechanism increases antibacterial effects.

Resistance mechanism:

In vitro studies show that resistance bacteria may grow slower when used in combination with sulfamethoxazol and trimethoprim compared to only using Sulfamethoxazol or Trimethoprim.

resistance to sulfamethoxazol can occur according to different mechanisms. Mutated bacteria increase PABA concentration and thus compete with sulfamethoxazole reducing the inhibition of enzyme dihydropteroate synthetase. Another resistance mechanism is that through plasmid intermediaries and leads to the production of transformed dihydropteroat enzymes Synthetase affinity with sulfamethoxazol decreased compared to normal enzymes.

resistance to trimethoprim occurs due to mutations through plasmid intermediaries, resulting in the production of transformed dihydrofolat enzymes that are affinity for trimethoprim to decrease compared to normal enzymes. Trimethoprim is associated with plasma DHFR but less tighter than bacterial enzymes. Its affinity with DHFR mammals is about 50,000 times lower than the bacterial enzyme.

Many pathogenic bacteria are often sensitive to trimethoprim and sulfamethoxazol on in vitro at lower concentrations of blood levels, tissue and urine after recommended dose.

antibacterial spectrum

Sensitive bacteria are common:

Aerobic Gram -positive bacteria: Staphylococcus aureus, Staphylococcus saprophyticus, Streptococcus pyogenes.

Aerobic gram -negative bacteria: En

Bacteria whose antibod antites can be a problem:

Aerobic Gram -positive bacteria: Enterococcus Faecalis, Enterococcus Faecium, Nocardia spp., Staphylococcus Epidermidis, Streptococcus Pneumoniae. Aerobic gram -negative bacteria: Citrobacter spp.

resistant bacteria:

Aerobic gram -negative bacteria: Pseudomonas Aeruginosa, Shigella spp., Vibrio Cholera.

pharmacokinetic

absorption

After taking Trimethoprim and Sulfamethoxazol, it is absorbed quickly and almost completely. The presence of food does not slow down the absorption. The peak concentration in the blood is reached for about 1-4 hours after eating and is related to the dose. Effective concentration for 24 hours after taking the dose of treatment. Stable concentration in adults achieved after taking the drug for 2-3 days.

distribution

about 50% trimethoprim in plasma is linked to protein. Trimethoprim concentration in tissue is usually higher in plasma, especially high in the lungs and kidneys.

The concentration of trimethoprim in bile, fluid and prostate tissue, saliva, sputum and vaginal fluid is higher than the plasma concentration. The concentration of drugs in aquatic, breast milk, cerebrospinal fluid, middle ear fluid, joint fluid and fluid (intestinal tract) reaches the level of treatment. Trimethoprim goes into amniotic fluid and fetal tissue to reach the concentration of the mother's plasma concentrations.

About 66% of sulfamethoxazol in plasma is linked to protein. The concentration of sulfamethoxazol is active in amniotic fluid, aquatic fluid, bile, cerebrospinal fluid, middle ear fluid, sputum, joint and tissue (interstitial fluid) about 20-50% of plasma concentrations.

transformation

The excretion of intact sulfamethoxazol in the kidney accounts for 15-30% of the dose. Sulfamethoxazol is metabolized more than trimethoprim, by acetylation, oxidation or glucuronid. In 72 hours, about 85% of the dose found in urine in the form of unchanged with main metabolites (N4-acetyl).

Elimination

Trimethoprim's waste time in men with normal kidney function is 8.6 - 17 hours. When creatinine clearance is less than 10 ml/minute, the sale time increases to 1.5 - 3.0 times. There is no significant difference in the sale time in elderly patients and young patients.

Trimethoprim is excreted mainly through the kidneys and about 50% of the dose is excreted in urine within 24 hours in constant form. Some metabolites have been determined in urine.

Salfamethoxazol's waste time in men with normal kidney function is about 9 - 11 hours. The sale time of the activity types of sulfamethoxazol does not change when the renal function decreases. However, the semi -cancellation time of acetyl metabolites will extend when the creatinine clearance is less than 25 ml/min.

sulfamethoxazol is excreted mainly through the kidneys; About 15% - 30% of the dose found in urine in the form of operation.

Pharmacokinetics in children with the normal kidney function of both trimethoprim and sulfamethoxazol ingredients depend on age. The elimination of the drug decreased in newborns, during the first two months, then both trimethoprim and sulfamethoxazol increased excretion with higher clearance and shorter selling time. In elderly patients sulfamethoxazol's clearance.

Sulfamethoxazol concentration tests in plasma after 2-3 days of using Cotrim 960 should be done on the samples obtained after 12 hours of medication.

If the concentration of sulfamethoxazol exceeds 150 mcg/ml to stop taking the drug until the concentration is below 120 mcg/ml.

pneumocystis jirovecii:

Dosage mode for treatment:

Children (> 12 years old to 18 years old): 100 mg of sulfamethoxazol + 20 mg trimethoprim/kg/day, divided into 2 or more drinking for 2 weeks. The goal is to achieve the peak concentration of trimethoprim in plasma or serum> 5mcg/ml.

Backup dosage mode:

Adults (18 years old):

Nocardia parasitic infection

Adults (> 18 years old): 3 - 4 capsules/day, in 3 months.

Toxoplasma infection

Dosage based on clinical experience. In case of prophylaxis, the recommended dose is like the case of Pneumocystis Jirovecii

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?

Nausea, vomiting, dizziness and confusion may be a sign of overdose. Bone marrow failure has been reported during the overdose of Trimethoprim.

How to handle

If the patient has no symptoms of vomiting, the method of vomiting may be used.

The gastric lavage also works to remove the drug from the body, although the absorption from the gastrointestinal tract is usually very fast and completely within about two hours. Depending on the condition of the kidney function, it may be accreted if the urine is low.

Both trimethoprim and the activity of sulfamethoxazol can be separated by hemolysis. The peritoneal part is not effective.

In an emergency, call the 115 emergency center immediately or go to the nearest local health station.

What to do when forgetting 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 dose to compensate for missed dose.

Precautions when using

death (though very rare) occurred due to severe reactions, including Stevens-Johnson syndrome, poisoned skin epidermis, spreading liver cell necrosis, leukopenia, abnormal anemia, other blood disorders and the hypersensitivity of the respiratory trail.

Life-threatening skin reactions such as Stevens-Johnson syndrome (SJS) and toxic skin epidermis (Ten) have been reported when using Trimethoprim combined with sulfamethoxazol.

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

If there are symptoms and signs of SJS or ten (for example, the skin rash often has blisters or mucosal lesions), should stop taking the drug.

For good control of SJS and Ten should diagnose early and stop any suspected drug.

If the patient has symptoms SJS or Ten while using trimethoprim and sulfamethoxazol, it is not used to repeat this drug.

Be careful when taking medicine for elderly patients because it is more likely to have more side effects and may be more seriously affected because these patients often have kidney failure, liver failure and/ or simultaneous use of other drugs.

For patients with renal impairment, caution should be taken and adjust the dose according to creatinine clearance.

Need to maintain the appropriate amount of urine. Crystal cases are very rare, although sulphonamid crystals have been found in urine of patients taking drugs. The risk of crystal can increase in malnourished patients.

Regularly monitor the number of blood cells when using trimethoprim and sulfamethoxazol for a long time or patients with folat or the elderly, as there may be abnormal changes in hematology index. Folic acid supplements should be considered during treatment but should also be cautious because it can affect anti -bacterial effect.

In patients with glucose-6-phosphate dehydrogenase (G-6-PD) patients, if the drug may experience hemolytic symptoms.

Be cautious when taking medication for patients with bronchial asthma or severe dermatitis.

Do not use trimethoprim and sulfamethoxazol in the treatment of throat sore throat due to streptococci beta group A hemolysis because the ability to kill bactericidal is less effective than penicillin.

trimethoprim reduces phenylalanin metabolism but this does not make sense for patients with durian phenylceton if the diet is appropriate.

avoid using cotrim 960 for patients who have identified or suspected the risk of porphyrin metabolism disorders. Both Trimethoprim and Sulfonamid are related to the increase in clinical porphyrin.

Strictly monitor potassium and sodium hematoma in patients at risk of hyperkalemia and hypoglycemia.

Cotrim 960 is associated with metabolic acidosis. Need to closely monitor metabolic acidosis if suspected

Do not use cotrim 960 for patients with serious hematological disorders, unless there is strict supervision. Cotrim 960 has been used in patients with cytotoxic poison treatment that has little or no side effects on the bone marrow or peripheral blood.

Cotrim 960 contains excipients with starch (containing gluten with very low content). Therefore, patients allergic to starch should not be used (except for celiac).

Using drugs for women during pregnancy and lactation

Using drugs for pregnant women

trimethoprim and sulfamethoxazol through the placenta and the safety of the drug for pregnant women has not been proven. Animal studies show that trimethoprim and sulfamethoxazol both cause abnormal fetuses. Therefore, drugs should not be taken during pregnancy, especially in the first 3 months, unless it is really necessary. In case of mandatory medication, it is necessary to use according to the doctor's instructions and supplement folat during treatment with cotrim 960.

sulfamethoxazol competes with bilirubin to attach to plasma albumin. When there is a significant increase in the mother's drug concentration in a few days, the risk of increased blood bilirubin in babies, especially in mothers near the birth. Therefore, avoiding drugs for pregnant women.

Using medicine for breastfeeding women

trimethoprim and sulfamethoxazol are excreted in breast milk. Cotrim 960 should not be used at the end of pregnancy and mothers who are breastfeeding or infants are at risk of increased blood bilirubin. In addition, avoid using cotrim 960 in newborns under 8 weeks because these children tend to increase blood bilirubin.

The effect of the drug on driving and operating machinery

There is no evidence of the effect of the drug on the ability to drive and operate machinery.

Interaction of drugs

Interaction with tests: Trimethoprim may affect serum/ plasma creatinine quantitative results when using alkaline picrat reactions (plasma creatinine evaluation results/ high serum 10%). Creatinine clearance decreases: Creatinine secretion in the renal tubules decreased from 23% to 9% while glomerular filtration remains unchanged.

Zidovudin: In some cases, simultaneous treatment with zidovudin may increase the risk of hematology side effects. If you have to simultaneously use cotrim 960 and zidovudin, it is necessary to closely monitor hematology parameters.

Cyclosporin: The impaired renal function has been reported in patients treated with cotrim 960 and cyclosporin after kidney transplant.

Rifampicin: Concomitant use of rifampicin and cotrim 960 reduces trimethoprim's waste time in plasma after about a week.

When used simultaneously trimethoprim with drugs forming cations in physiological pH, and also partially excreted by the active excretion in the kidneys (for example, Procainamid, Amantadin), capable of inhibiting competitive mutual competition. Therefore increasing the plasma concentration of one or both drugs.

Diuretics (thiazid): In elderly patients, simultaneously with diuretics, mainly thiazid, may increase the risk of thrombocytopenia with or without hemorrhage.

pyrimethamine: There has been a report that patients using pyrimethamine higher dose than 25 mg per week may have huge red blood cell anemia should be indicated simultaneously with cotrim 960.

Warfarin: Cotrim 960 increases Warfarin's anticoagulant activity through the selective inhibition of its metabolic process. Sulfamethoxazol can remove warfarin from albumin bonding proteins in test tubes. Therefore, careful control of anticoagulants during treatment with cotrim 960.

Phenytoin: Cotrim 960 extends the selling time of phenytoin and if used simultaneously can lead to increased phenytoin efficiency. Need to closely monitor patient condition and serum phenytoin concentration.

Digoxin: The use of trimethoprim along with digoxin increases plasma digoxin concentrations in some elderly patients.

Methotrexate: Cotrim 960 may increase methotrexate levels in plasma.

If cotrim 960 is indicated in patients taking anti -folat drugs such as methotrexate, should consider supplementing folat.

trimethoprim affects serum methotrexate quantitative dihydrofolate reducing method from lactobacillus casei. With the quantitative method by radioactive test will not be affected.

lamivudin: Using trimethoprim increases 40% of lamivudin pharmacokinetics.

lamivudin does not affect the pharmacokinetics of trimethoprim or sulfamethoxazol.

Hypoglycemic drugs: The interaction with sulphonylurea hypoglycemic drugs is not common but there has been a report on increasing potential.

Hemorrhage hyperpass: Caution should be used when taking drugs that can cause hyperkalemia.

Repaglinid: Trimethoprim may increase the pharmacokinetics of repaglinid, leading to hypoglycemia.

Folic acid: Folic acid supplements can effectively affect the antibiotic effect of trimethoprim and sulfamethoxazol. This has been reported in the prophylaxis and treatment of pneumocystis jirovecii pneumonia.

Birth control pills: Failure to oral contraceptives have been reported when used simultaneously with antibiotics. The mechanism of this effect is not clear. Women treated with antibiotics should temporarily use other contraceptive methods.

Tyeum of drugs

Due to the absence of studies on the correlation of the drug, not mixing this drug with other drugs.