anavar results

Bactrim contains two active substances that have a synergistic effect by blocking two enzymes catalyzing successive stages folinic acid biosynthesis in microorganisms. Through this mechanism, in vitro bactericidal effect is achieved at concentrations such that the individual components of the preparation have a bacteriostatic effect. In addition, Bactrim often effective against pathogens which are resistant to one of its components.

In vitro antibacterial activity Bactrim covers a broad spectrum of gram-positive and gram-negative pathogens, although the sensitivity might depend on the geographical location.

Cocchi: Branhamella catarrhalis .

Gram-negative microorganisms: of Haemophilus influenzae (b-and b-laktamazoobrazuyuschie laktamazoneobrazuyuschie strains), of Haemophilus parainfluenzae, E. The coli, Citrobacter freundii, other types of Citrobacter, Klebsiella pneumoniae, Klebsiella oxytoca, other types of Klebsiella, Enterobacter cloaceae, Enterobacter aerogenes, Hafnia alvei, Serratia marcescens, Serratis liquefaciens, other speciesSerratia, Proteus mirabilis, Proteus vulgaris, Morganella morganii,, Shigella spp., Yersinia enterocolitica , other Yersinia, Vibrio cholerae.

Various gram-negative microorganisms: Edwardsiella tarda , of Alcaligenes faecalis , of Pseudomonas cepacia , Burkholderia ( of Pseudomonas ) pseudomallei .

Clinical experience shows that may be sensitive and Brucella spp., Listeria monocytogenes, Nocardia asteroides., Pneumocystis carinii, Cyclospora cayetanensis.

Partially sensitive pathogens ( MIC = 80-160 mg / l sulfamethoxazole)

Cocci: of Staphylococcus aureus (methicillin-susceptible strains and metitsillinoustoychivye), of Staphylococcus spp . and penitsillinoustoychivye strains).

Gram-negative bacilli: of Haemophilus ducreyi , Providentia rettgeri , other types of Providentia, of Salmonella typhi, of Salmonella enteritidis, Stenotrophomonas maltophilia are (formerly known asXanthomonas maltophilia).

Various gram-negative microorganisms: of Acinetobacter lwoffi , of Acinetobacter anitratus (mainly, A baumanii. ), The Aeromonas hydrophilia .

Pathogens resistant (MIC> 160 mg / l for sulfamethoxazole)

Mycoplasma spp., Mycobacterium tuberculosis, Treponema pallidum.

If Bactrim assigned empirically, it is necessary to take into account local characteristics of resistance to Bactrim possible causative agents of a particular infectious disease.

For infections that can be caused in part by susceptible microorganisms, it is recommended to test for sensitivity to eliminate the pathogen resistance.

Sensitivity to Bactrim can be determined by standard methods, for example, by disk or dilution method recommended by the National Committee for Clinical Laboratory Standards (NKKLS).

NKKLS recommends the following sensitivity criteria:

 

* Method discs, diameter of inhibition zone (mm) dilution method ** MIC (mcg / mL)
trimethoprim sulfamethoxazole
sensitive

Partially sensitive

sustained

≥ 16

11-15

≤ 10

≤ 2

4

≥ 8

≤ 38

76

≥ 152

* Disk: 1.25 mg of trimethoprim and 23.75 mg sulfamethoxazole.

** Trimethoprim and sulfamethoxazole in the ratio of 1:19.

 

Pharmacokinetics

Suction

After oral administration trimethoprim and sulfamethoxazole is rapidly and almost completely absorbed in the upper gastrointestinal tract. After 1-4 hours after a single dose of 160 mg trimethoprim + 800 mg sulfamethoxazole trimethoprim maximum concentration in plasma is 1.5-3 ug / ml, and sulfamethoxazole – 40-80 mg / ml. Repeated reception with 12 hours apart minimum equilibrium concentrations of 2-3 days stabilized within 1.3-2.8 ug / ml for trimethoprim and 32-63 mg / ml for sulfamethoxazole.

Distribution

Trimethoprim distribution volume is about 130 liters, sulfamethoxazole – about 20 liters. 45% and 66% of trimethoprim sulfamethoxazole bound to plasma proteins.

Trimethoprim is somewhat better than sulfamethoxazole penetrates nevospalennuyu prostate tissue, semen, vaginal secretions, saliva, healthy and inflamed lung tissue, bile, while equally penetrate into the cerebrospinal fluid and aqueous humor eye, both components of the preparation.

Large amounts of trimethoprim and sulfamethoxazole somewhat smaller amount of flow coming into the interstitial extravasal and other body fluids, wherein the concentration of trimethoprim and sulfamethoxazole exceed minimum inhibitory concentration for most pathogens.

In humans, trimethoprim and sulfamethoxazole detected in placenta, umbilical cord blood, amniotic fluid, and fetal tissues (liver, lungs), indicating that both the penetration of substances through the placental barrier. As a rule, trimethoprim concentrations in the fetus are similar to those of the mother, and sulfamethoxazole concentrations in the fetus is lower than that of the mother.

Both substances are excreted in breast milk. Concentrations similar to breast milk (TMP) or below (sulfamethoxazole) those in maternal plasma.

Metabolism

Approximately 50-70% of the dose of trimethoprim and sulfamethoxazole 10-30% of the dose is excreted unchanged. The major metabolites of trimethoprim are 1- and 3-oxides and the 3′- and 4′-hydroxy derivatives. Some metabolites have antimicrobial activity. Sulfamethoxazole metabolized in the liver, principally by N 4 -atsetilirovaniya and to a lesser extent by conjugation with glucuronic acid.

breeding

The half-life of the two components are very close to each other (on average, 10 hours for trimethoprim and 11 hours for the sulfamethoxazole).

Both compounds and their metabolites are derived almost exclusively through the kidneys by glomerular filtration like and tubular secretion, thus both active substances in the urine concentration significantly higher than in blood. A small part of the active substance is excreted in the feces.

 

Pharmacokinetics in special clinical situations

In elderly patients, as well as severe renal failure (creatinine clearance of 15-30 ml / min), the drug half-lives of both components increase, requiring dose adjustment.

 

testimony

 

Bactrim should be used only in those cases where, in the opinion of the physician, the benefit of such therapy outweighs the potential risk; you must resolve the issue of whether to manage the use of effective anti-bacterial agent is impossible.

Since the sensitivity of bacteria to antibiotics in vitro changes in different geographical areas and over time, the local characteristics of bacterial sensitivity to consider when choosing a product.

Respiratory tract infections and upper respiratory tract: acute exacerbations of chronic bronchitis, otitis media in children, if there are enough reasons to prefer a combination of trimethoprim and sulfamethoxazole monotherapy antibiotic. Treatment and prevention (primary and secondary), pneumonia caused by Pneumocystis carinii, in adults and children.

Infections of the urinary tract: urinary tract infection, chancroid.

Infections of the gastrointestinal tract: typhoid and paratyphoid fever, shigellosis (caused by susceptible strains of Shigella flexneri and of Shigella sonnei , if shown antibacterial therapy), travelers’ diarrhea caused by enterotoxic strains of Escherichia coli, cholera (in addition to the replenishment fluid and electrolytes).

Other bacterial infections: infections caused by a variety of microorganisms (possible combination with other antibiotics), such as brucellosis, acute and chronic osteomyelitis, nocardiosis, actinomycosis, toxoplasmosis and South American blastomycosis.

Contraindications:

Severe lesions of the liver parenchyma; severe renal insufficiency (creatinine clearance <15 mL / min), if you can not regularly determine the concentration of drug in plasma; blood disorders (aplastic anemia, B12 deficiency anemia, agranulocytosis, leukopenia); hypersensitivity to the drug in history; in conjunction with dofetilide; Children up to age 12 years; deficiency of glucose-6-phosphate dehydrogenase.

 

Carefully

 

Porphyria, thyroid dysfunction, asthma, folic acid deficiency.

 

Pregnancy and lactation

In animals, very high doses of trimethoprim and sulfamethoxazole cause fetal malformations typical of folic acid deficiency.

According to studies in pregnant women, literature reviews and specific messages about the evils of receiving Bactrim, apparently, is not coupled with a significant risk of teratogenicity for the person.

Because both trimethoprim and sulfamethoxazole cross the placental barrier and thus may affect folate metabolism, during pregnancy Bactrim should be used only if the expected benefit from its application exceeds the potential risk to the fetus. Pregnant women receiving Bactrim, recommended to appoint 5 mg of folic acid per day. In the later stages of pregnancy to avoid the use of Bactrim due to the possible risk of kernicterus in neonates.

As trimethoprim and sulfamethoxazole penetrate into breast milk. Despite the fact that breast milk gets a small amount of Bactrim to the child, it is recommended to compare the potential risk to the infant (kernicterus, hypersensitivity) to the expected therapeutic effect for the mother.

Dosage and administration:

Inside, after a meal with plenty of fluids.

 

standard dosing

Adults and children over 12 years:

 

Film-coated anavar results
morning evening
The standard dose 1 1
Minimum dose and dose

for long-term treatment

(Over 14 days)

0.5 0.5
Higher dose (in

severe cases)

1.5 1.5

 

Duration of treatment

In acute infections, Bactrim should be appointed for a term of not less than 5 days or as long as the symptoms of the patient will not be missing for 2 days. If after 7 days of treatment clinical improvement does not occur, you should re-evaluate the patient’s condition for a possible correction treatment.

 

Special dosage instructions

Chancroid

1 tablet twice a day. If after 7 days of healing skin member does not occur, therapy can extend for another 7 days. However, it should be borne in mind that the lack of effect may be indicative of the pathogen resistance.

Acute uncomplicated urinary tract infections

Women with acute uncomplicated urinary tract infections recommended single dose of 2-3 anavar results. If possible, they should be taken in the evening after a meal or before bedtime.

Patients on hemodialysis

After receiving the usual loading dose, subsequent doses should be half or a third of the standard and administered every 24-48 hours.

Pneumonia caused by Pneumocystis carinii

Divided into equal doses up to 20 mg of trimethoprim and 100 mg sulfamethoxazole per kg body weight per day, every 6 hours for 14 days.

The upper limit of the dose is determined according to the following table:

 

 

Body Weight in kg Doses taken at intervals of 6 hours

film-coated anavar results

32 1
40
48 1.5
64 2
80 2.5

For the prevention of pneumonia caused by of Pneumocystis carinii , in adults and adolescents (over 12 years) it is recommended to appoint 1 tablet per day. In children, for the prevention of pneumonia caused by Pneumocystis carinii, you should use a different dosage form of the drug Bactrim – oral suspension. Nocardiosis

Adults 3-4 anavar results for at least 3 months. The dose should be adjusted according to age, patient weight, and severity of the kidney disease. Sometimes the treatment is continued until 18 months.

Patients with impaired renal function

When creatinine clearance> 30 mL / min are usually prescribed dose at creatinine clearance 15-30 ml / min – half the usual dose and Bactrim is not recommended for creatinine clearance <15 mL / min.

Sick elderly

With normal kidney function the usual dose prescribed for adults.

Side effect:

The recommended dose Bactrim is usually well tolerated. The most common side effects are skin rash and gastrointestinal disorders.

Body as a Whole

Described hypersensitivity reactions. As with any other drug treatment in patients with hypersensitivity to the drug can develop an allergic reaction: fever, angioedema, anaphylactoid reactions, serum sickness, in rare cases – pulmonary infiltrates on the type of eosinophilic or allergic alveolitis. They can be clinically manifested cough and shortness of breath. With the sudden appearance or growth of such symptoms and the patient should be examined to consider the termination of Bactrim therapy. In rare cases there is a periarteritis nodosa and allergic myocarditis. Cases of fungal infections such as candidiasis.

The following side effects may occur in order of decreasing frequency.

Skin: adverse reactions usually disappear poorly expressed and rapidly after discontinuation of the drug. As with other drugs containing sulfonamides, Bactrim, in rare cases, can cause photosensitivity, development of erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome) and Henoch-Schönlein purpura.

Gastrointestinal tract : nausea (with or without vomiting), stomatitis, diarrhea, liver necrosis, rare cases of hepatitis, cholestasis, glossitis, pseudomembranous enterocolitis individual cases, increase of transaminases and bilirubin, isolated cases of the syndrome of “vanishing bile duct.” Cases of acute pancreatitis during treatment with Bactrim, but few of these patients suffered from serious diseases, including AIDS.

Hematological changes: leukopenia, neutropenia, granulocytopenia and thrombocytopenia (most are mild or asymptomatic and disappear after discontinuation of the drug); very rarely – agranulocytosis, anemia (megaloblastic, hemolytic / or autoimmune aplastic), methemoglobinemia, pancytopenia or purpura.

Urinary tract : rarely – renal failure, interstitial nephritis, increased blood urea nitrogen, serum creatinine, crystalluria. Sulfonamides, including Bactrim, may lead to increased diuresis, especially in patients with edema of cardiac origin.

Nervous System: neuropathy (including peripheral neuritis and paresthesia), hallucinations, uveitis, rare cases of aseptic meningitis or meningeal symptoms, ataxia, seizures, systemic and non-systemic vertigo.

Respiratory System: isolated cases of pulmonary infiltrates, such as those that occur in eosinophilic or allergic alveolitis. They may manifest symptoms such as cough or shortness of breath. With the sudden appearance or growth of these symptoms need to re-examine the patient and consider discontinuing treatment Bactrim.

Musculoskeletal system : rarely – arthralgia and myalgia, isolated cases of rhabdomyolysis reported.

Metabolism: high doses of trimethoprim used to treat Pneumocystis carinii pneumonia lead to a progressive but reversible increase in serum potassium in a significant number of patients. Hyperkalemia can cause

even receiving the recommended dose of trimethoprim, if it is administered on a background of violations

potassium metabolism, renal failure or simultaneously taking drugs that provoke hyperkalemia. These patients should be regularly monitored content of potassium in serum. Cases of hyponatremia. In individuals without diabetes and receiving trimethoprim-sulfamethoxazole, and occasionally cases of hypoglycemia occur, usually a few days after the start of treatment. The risk of hypoglycemia was higher in patients with impaired renal function, liver disease, malnutrition or receiving large doses of trimethoprim-sulfamethoxazole.

Adverse Reactions in AIDS patients. The incidence of adverse events, particularly rash, fever, leukopenia, and elevated serum transaminase activity in AIDS patients, significantly higher than those from individuals not suffering from AIDS.

Overdose:

Symptoms of acute overdose: nausea, vomiting, diarrhea, headache, dizziness, intellectual and visual disorders, in severe cases – crystalluria, hematuria and anuria.

Symptoms of chronic overdose: inhibition of hematopoiesis (anemia, leukopenia), as well as other pathological changes in the blood picture due to lack of folinic acid.

Treatment (depending on symptoms): measures to prevent further absorption of the drug, increasing renal excretion by forced diuresis (urine alkalinization promotes the excretion of sulfamethoxazole), dialysis (peritoneal dialysis is ineffective). It is necessary to control blood picture and electrolytes. When expressed pathological changes in the blood picture or jaundice prescribe specific treatment. To eliminate the action of trimethoprim on hematopoiesis calcium folinate can be administered at a dose of 3-6 mg / m for 5-7 days.

 

Interaction with other drugs

 

In patients with middle and old age, at the same time taking certain diuretics (mainly thiazides), observed increased incidence of thrombocytopenia.

Bactrim may increase digoxin serum concentrations, especially in elderly patients, therefore, requires monitoring of digoxin serum concentrations.

Bactrim may enhance anticoagulant effect of warfarin. On the possibility of such an interaction should be borne in mind when appointing Bactrim patients who are already receiving anticoagulants. In such cases it is necessary to re-determine the clotting time.

Bactrim may inhibit the hepatic metabolism of phenytoin. Following the appointment of Bactrim in normal clinical doses there was an increase in half-life of phenytoin by 39% and reducing its rate of metabolic clearance of 27%. When concomitant administration of both drugs it is important to monitor the toxic effects of phenytoin.

In patients receiving trimethoprim-sulfamethoxazole and cyclosporin following renal transplantation, there may be a reversible deterioration of renal function, manifested by increased serum creatinine.Probably, this effect is caused by trimethoprim. In patients with normal renal function was observed reversible decrease in creatinine clearance, which may be due to reversible inhibition of tubular secretion of creatinine.

Bactrim may decrease the effectiveness of tricyclic antidepressants.

Sulfonamides, including sulfamethoxazole, can compete for binding with proteins and renal transport of methotrexate, thus increasing the concentration of free methotrexate and systemic effect.

In patients taking trimethoprim and methotrexate, pancytopenia cases have been described. Trimethoprim has a low affinity for the human dihydrofolate, but can enhance the toxicity of methotrexate, especially in the presence of other risk factors such as old age, hypoalbuminemia, renal failure, bone marrow suppression. These side effects are more likely if methotrexate is administered in high doses. To prevent myelosuppression recommended to appoint such patients folic acid and calcium folinate.

We can assume that while the appointment Bactrim patients receiving pyrimethamine for malaria prophylaxis in doses exceeding 25 mg per week, they may develop megaloblastic anemia.

Like other sulfonamides, Bactrim may potentiate the action of oral antidiabetic drugs.

Trimethoprim, inhibiting the transport system of the kidneys, increases the area under the curve “concentration – time» AUC by 103% and the maximum concentration of 93% dofetilide. With increasing concentrations of dofetilide may cause serious ventricular arrhythmias with a lengthening of the QT interval, including arrhythmia of torsades de pointes . Co-administration of trimethoprim and dofetilide contraindicated.

In patients taking indomethacin, may increase the concentration of sulfamethoxazole in the blood.
We describe a case of toxic delirium after simultaneously receiving trimethoprim-sulfamethoxazole and amantadine.

Laboratory research

Bactrim, and in particular its constituent trimethoprim can affect the results of determination of serum concentration of methotrexate conducted by competitive protein binding bacterial dihydrofolate using as ligand. However, the determination of methotrexate radioimmunoassay interference does not occur.

Trimethoprim and sulfamethoxazole can also affect the results of the Jaffe reaction (creatinine determination reaction with picric acid in an alkaline medium) with a normal range of approximately overestimated by 10%.

special instructions

 

The first appearance of skin rash or any other severe adverse drug reactions should be discontinued. In patients with a tendency to allergic reactions and asthma Bactrim should be used with caution.

Duration of treatment Bactrim should be as short as possible, especially in patients with middle and old age. If it affects the kidneys the dose should be adjusted according to section “Dosage in special cases.”

With long-term appointment Bactrim should regularly determine the number of blood cells. With a significant decrease in the number of all blood cells Bactrim should be discontinued. Patients with severe hematological diseases Bactrim can be given only in exceptional cases.

In patients with middle and old age, as well as in patients with existing folic acid deficiency or kidney failure, can occur hematological changes characteristic of lack of folic acid. They disappear after administration of folinic acid.

Patients receiving long-term treatment Bactrim (particularly in renal failure), you must make regular urinalysis and monitor renal function. During the treatment it is necessary to provide sufficient fluid flow in the body and to prevent adequate diuresis crystalluria.

Because of the possibility of hemolysis Bactrim can be given to patients with a deficiency of glucose-6-phosphate dehydrogenase only if absolutely indicated and in minimal doses.

Trimethoprim violates the exchange of phenylalanine, but this does not affect patients with phenylketonuria, subject to an appropriate diet.

As with any appointment sulfonamides, caution should be exercised in patients with porphyria or thyroid dysfunction.

Patients for metabolism which is characterized by “slow acetylation,” more likely to develop idiosyncrasy to sulfonamides. danabol ds 10