Bactrim - instructions for use, doses, side effects, contraindications

Excipients: cellulose dispersible - 80.0 mg, megylparahydroxybenzoate - 2.5 mg, propyl parahydroxybenzoate - 0.5 mg,sorbitol - 4500.0 mg, polysorbate 80 - 10.0 mg, vanilla flavor - 10.0 mg, banana flavor - 25.0 mg, water purified to 5.0 ml.

Description:Homogeneous suspension from yellowish-white to orange with a fruity odor.

Pharmacotherapeutic group:Antimicrobial combination

ATX: & nbsp

J.01.E.E.01 Co-trimoxazole [sulfamethoxazole in combination with trimethoprim]

Pharmacodynamics:Combined bactericidal chemotherapeutic agent

Bactrim® contains two active substances that have a synergistic effect, blocking two enzymes that catalyze the sequential stages of folinic acid biosynthesis in microorganisms. Thanks to this mechanism, bactericidal action in vitro is achieved at concentrations in which individual components of the drug have only a bacteriostatic effect. In addition, Bactrim® is often effective against pathogens that are resistant to one of its components. In vitro the antibacterial action of the drug Bactrim® covers a wide range of gram-positive and gram-negative pathogens,although the sensitivity may depend on the geographical location.

Usually sensitive pathogens (IPC <80 mg / l for sulfamethoxazole)

Kokki: Branhamella catarrhalis.

Gram-negative microorganisms: Haemophilus influenzae (ßlactamase-forming and ß-lactamase-forming strains), Haemophilus parainfluenzae, E. coli, Citrohacter freundii, other types Citrobacter, Klebsiella pneumoniae, Klebsiella oxytoca, other types Klebsiella, Enterobacter cloaceae, Enterobacter aero genes, Hafnia alvei, Serratia marcescens, Serratis liquefaciens, other types Serratia, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Shigella spp., Yersinia enterocolitica, other types Yersinia, Vibrio cholerae.

Various Gram-negative microorganismsare: Edwardsiella tarda, Alcaligenes faecalis, Pseudomonas cepacia, Burkholderia (Pseudomonas) pseudomallei.

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

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

Kokki: Staphylococcus aureus (methicillin-sensitive and methicillin-resistant strains), Staphylococcus spp. (coagulase negative), Streptococcus pneumoniae (penicillin-sensitive and penicillin-resistant strains).

Gram-negative sticks: Haemophilus ducreyi, Providentia rettgeri, other types Providentia, Salmonella typhi. Salmonella enteritidis, Stenotrophomonas maltophilia (previously called Xanthomonas maltophilia). Different gram-negative microorganisms: Acinetobacter Iwoffi, Acinetobacter anitratus (mainly, A. baumanii), Aeromonas hydrophilia.

Sustainable pathogens (MIC> 160 mg / l for sulfamethoxazole)

Mycoplasma spp., Mycobacterium tuberculosis, Treponema pallidum.

If the preparation Bactrim® is empirically prescribed, it is necessary to take into account local peculiarities of resistance to the Bactrim® preparation of possible pathogens of a particular infectious disease.

In infections that can be caused by partially sensitive microorganisms, it is recommended that the sample be tested for sensitivity in order to exclude the resistance of the pathogen.

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

The BCC recommends the following criteria sensitivity:

	Disc method*,	The breeding method **, MPK (μg / ml)
	diameter of the growth inhibition zone (mm)	trimethoprim	sulfamethoxazole
Sensitive	≥16	≤2	≤38
Partially sensitive	11-15	4	76
Sustainable	≤10	≥8	≥152

* Disk: 1.25 μg of grimethoprim and 23.75 μg of sulfamethoxazole.

** Trimethoprim and sulfamistoxazole in the ratio 1:19.

Pharmacokinetics:Suction

After oral administration, trimethoprim and sulfamethoxazole are rapidly and almost completely absorbed in the upper part of the gastrointestinal tract. 1-4 hours after a single administration of 160 mg of trimethoprim plus 800 mg of sulfamethoxazole, the maximum concentrations of trimethoprim in the plasma are 1.5-3 μg / ml, and sulfamethoxazole 40-80 μg / ml. With repeated administration with an interval of 12 hours, the minimum equilibrium concentrations after 2-3 days stabilize within 1.3-2.8 μg / ml for tRimetoprim and 32-63 μg / ml for sulfamethoxazole.

Distribution

The volume of distribution of trimethoprim is about 130 liters, sulfamethoxazole is about 20 liters. 45% of trimethoprim and 66% of sulfamethoxazole are associated with plasma proteins. Trimethoprim is somewhat better than sulfamethoxazole penetrates into the non-inflamed prostate tissue, seminal fluid, vaginal secretions, saliva, healthy and inflamed lung tissue, bile, while in the cerebrospinal fluid and watery eyes, both components of the drug penetrate equally.

Large amounts of trimethoprim and slightly lower amounts of sulfamethoxazole come from the bloodstream into the interstitial and other extravasal body fluids, with concentrations of trimethoprim and sulfamethoxazole exceeding the minimum inhibitory concentrations for most pathogens.

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

Both substances are excreted in breast milk.Concentrations in breast milk are close (trimethoprim) or lower (sulfamethoxazole) such in the mother's plasma.

Metabolism

Approximately 50-70% of the dose of trimethoprim and 10-30% of the dose of sulfamethoxazole is excreted unchanged. The main metabolites of trimethoprim are 1- and 3-oxides and 3'- and 4'-hydroxy derivatives. Some metabolites have antimicrobial activity. Sulfamethoxazole is metabolized in the liver, mainly by N₄-acetylation and, to a lesser extent, conjugation with glucuronic acid.

Excretion

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

Both substances, as well as their metabolites, are excreted almost exclusively through the kidneys, both by glomerular filtration and tubular secretion, so that the concentrations of both active substances in the urine are significantly higher than in the blood. A small part of the active substances is excreted with feces.

Pharmacokinetics in special clinical cases

Patients of elderly and senile age

With normal kidney function, the half-life of both components of the drug varies insignificantly.

Patients with impaired renal function

In patients with renal insufficiency (creatinine clearance 15-30 ml / min), the half-lives of both components of the drug increase, which requires dose adjustment.

Indications:

Bactrim® should be prescribed only in those cases when, in the opinion of the doctor, the advantage of such therapy exceeds the possible risk; it is necessary to decide whether one effective antibacterial agent can be dispensed with. Because the sensitivity of bacteria to antibiotics in vitro changes in different geographical areas and in time, when choosing a drug, local peculiarities of bacterial sensitivity should be taken into account.

Respiratory tract infections and ENT organs: exacerbation of chronic bronchitis, otitis media in children, if there is sufficient reason to prefer a combination of trimethoprim and sulfamethoxazole monotherapy with an antibiotic. Treatment and prevention (primary and secondary) of pneumonia caused by Pneumocystis carinii, the adults and children.

Urinary tract infections: urinary tract infection, mild chancroid.

Infections of the gastrointestinal tract: typhoid fever and paratyphosis, shigellosis (caused by susceptible strains Shigella flexneri and Shigella sonnei, if antibiotic therapy is indicated), travelers' diarrhea caused by enterotoxic strains Escherichia coli, Cholera (in addition to replenishment of fluid and electrolytes).

Other bacterial infections: infections caused by a number of microorganisms (possibly a combination with other antibiotics), for example: brucellosis, acute and chronic osteomyelitis, nocardiosis, actinomycosis, toxoplasmosis and South American blastomycosis.

Contraindications:Pronounced lesions of the liver parenchyma; severe renal failure (creatinine clearance <15 ml / min), if it is not possible to regularly determine plasma concentrations of the drug; blood diseases (aplastic anemia, B 12-deficiency anemia, agranulocytosis, leukopenia); hypersensitivity to the components of the drug in the anamnesis; in combination with dofetilide; deficiency of glucose-6-phosphate dehydrogenase.

Carefully:

Porphyria, dysfunction of the thyroid gland, bronchial asthma, deficiency of folic acid.

Pregnancy and period of breastfeeding.

Pregnancy and lactation:

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

According to studies in pregnant women, literature reviews and individual reports of malformations, the reception of Bactrim®, apparently, is not associated with a significant risk of teratogenicity for a person.

Since both trimethoprim and sulfamethoxazole penetrate the placental barrier and, thus, can affect the metabolism of folic acid, in pregnancy Bactrim® should be prescribed only if the expected benefit from its use exceeds the possible risk to the fetus. Pregnant women receiving Bactrim®, it is recommended to appoint 5 mg of folic acid per day. At the late pregnancy should be avoided Bactrim® because of the possible risk of nuclear jaundice in newborns.

Both trimethoprim and sulfamethoxazole penetrate into breast milk. Despite the fact that a small amount of Bactrim gets to the baby with breast milk, it is recommended to compare the possible risk for an infant (nuclear jaundice,hypersensitivity) with the expected therapeutic effect for the mother.

Dosing and Administration:

Inside, after eating with a sufficient amount of liquid.

Standard dosing

	Suspension for oral administration, measuring spoons
	morning	evening
Standard dose	4	4
The minimum dose and dose for long-term treatment (more than 14 days)	2	2
Increased dose (in particularly severe cases)	6	6

Continuation of treatment

For acute infections, Bactrim® should be given for a period of at least 5 days or until symptoms are not present within 2 days. If after 7 days of therapy there is no clinical improvement, the patient's condition should be reassessed for possible correction of treatment.

Dosing in special cases

Chancroid

4 scoops of suspension twice a day. If after 7 days of skin healingThere is no such thing as an additional element, and the therapy can be extended for another 7 days. However, it should be borne in mind that the lack of effect may indicate resistance of the pathogen.

Acute uncomplicated urinary tract infections

Women with acute uncomplicated urinary tract infections are recommended to take a single dose of 8-12 measuring spoons of the suspension.If possible, they should be taken in the evening after a meal or before going to bed.

Patients on hemodialysis

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

Pneumonia caused by Pneumocystis carinii

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

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

Body weight, kg	Doses taken at intervals of 6 hours, measuring spoons (ml)
8	1 (5 ml)
16	2 (10 ml)
24	3 (15 ml)
32	4 (20 ml)
40	5 (25 ml)
48	6 (30 ml)
64	8 (40 ml)
80	10 (50 ml)

For the prevention of pneumonia caused by Pneumocystis carinii, Adults and adolescents (over 12 years of age) should be prescribed 4 scoops of suspension per day. For children, a dose of trimethoprim 150 mg / m is recommended²/ day and sulfamethoxazole 750 mg / m²/ day, divided into two equal doses, for 3 consecutive days every week. The total daily dose of ns should exceed 320 mg of trimethoprim and 1600 mg of sulfamethoxazole. You can use the following instructions:

Body surface area	Doses taken with an interval of 12 hours, measuring spoons (ml)
0.26	0.5 (2.5 mL)
0.53	1 (5 ml)
1.06	2 (10 ml)

Children

Children from 6 weeks to 5 months - 0.5 scoop suspension for oral administration twice a day (morning and evening), from 6 months to 5 years - 1 scoop twice a day, 6 to 12 years - 2 scoops twice a day. This dosage regimen approximately corresponds to a daily dose of 6 mg of trimethoprim and 30 mg of sulfamethoxazole per kg of body weight.

When Severe dose infections for children can be increased by 50%.

Nocardiosis

Adults for 12-16 measuring spoons of the suspension for at least 3 months. The dose should be adjusted depending on the age, body weight of the patient, kidney function and the severity of the disease. Sometimes treatment lasts up to 18 months.

Patients with impaired renal function

When the creatinine clearance is> 30 ml / min, the usual dose is prescribed, with creatinine clearance of 15-30 ml / min - half the usual dose, and with creatinine clearance <15 ml / min, Bactrim® is not recommended.

Patients of elderly and senile age

With normal kidney function, the usual dose for adults is prescribed.

Side effects:In recommended doses, Bactrim® is usually well tolerated. The most common side effects are skin rash and gastrointestinal disorders.

From the body as a whole

The reactions of hypersensitivity are described.As with any other drug, patients with hypersensitivity to the components of the drug may develop allergic reactions: fever, angioedema, anaphylactoid reactions, serum sickness, in rare cases - pulmonary infiltrates like eosinophilic or allergic alveolitis. They can be clinically manifested by coughing and shortness of breath. In case of sudden appearance or increase of such symptoms, the patient should be examined and consider stopping therapypreparation Bactrim®. In rare cases, there was nodular periarteritis and allergic myocarditis. Cases of fungal infections, such as candidiasis, are described.

In order of decreasing frequency, the following side effects can occur.

From the skin: Adverse reactions are usually mild and disappear quickly after drug withdrawal. Like other preparations containing sulfonamides, the Bactrim® preparation in rare cases can lead to photosensitization, development of erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), and purpura of Shenlen-Henoch, drug rash with eosipophilia and systemic manifestations (DRESS syndrome).

From the gastrointestinal tract: nausea (with or without vomiting), stomatitis, diarrhea, liver necrosis, rare cases of hepatitis, cholestasis, glossitis, isolated cases of pseudomembranous enterocolitis, increased activity of hepatic transaminases and bilirubin concentrations, isolated cases of the "disappearing bile duct" syndrome. Cases of acute pancreatitis have been described against the backdrop of treatment with Bactrim®, but several of these patients suffered from severe diseases, including acquired immunodeficiency syndrome (AIDS).

From the hematopoiesis: leukopenia, neutropenia, granulocytopenia and thrombocytopenia (most often weak or asymptomatic and disappear after drug withdrawal); very rarely - agranulocytosis, anemia (megaloblastic, hemolytic / autoimmune or aplastic), methemoglobinemia, pancytopenia or purpura.

From the urinary system: in rare cases - renal dysfunction, interstitial nephritis, increased blood urea nitrogen, serum creatinine, crystalluria. Sulfoamides, including Bactrim®, may lead to an increase in diuresis, especially in patients with cardiac edema.

From the nervous system: neuropathy (including peripheral neuritis and paresthesia), hallucinations, uveitis, are rare cases of aseptic meningitis or meningeal symptoms, ataxia, seizures, systemic and non-systemic dizziness.

From the respiratory system: individual cases of pulmonary infiltrates, similar to those that occur with eosinophilic or allergic alveolitis. They can manifest themselves with symptoms such as cough or shortness of breath. If you suddenly appear or increase this symptomatology, you need to re-examine the patient and consider stopping treatment with Bactrim®.

From the side of the musculoskeletal system: rarely - arthralgia and myalgia, individual cases of rhabdomyolysis are described.

From the side of metabolism: large doses of trimethoprim used for the treatment of PCP lead to a progressive but reversible increase in serum potassium in a significant number of patients. Hyperkalemia can cause even the intake of recommended doses of trimethoprim if it is prescribed against a background of potassium metabolism, kidney failure, or simultaneous reception of drugs provoking hyperkalemia. These patients need to regularly monitor the potassium content in the serum.Cases of hyponatremia are described. In people who do not suffer from diabetes and receive trimethoprim-sulfamethoxazole, occasional cases of hypoglycemia occur, usually within a few days of starting treatment. The risk of hypoglycemia is higher in patients with impaired renal function, liver disease, malnutrition or receiving large doses of trimethoprim-sulfamethoxazole

Adverse reactions in patients with AIDS. The incidence of adverse events, especially rash, fever, leukopenia and increased activity of hepatic aminotransferases in serum in AIDS patients, is significantly higher than those in non-AIDS patients.

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: oppression hemopoiesis (thrombocytopenia, leukopenia), as well as other pathological changes in the blood picture due to folic acid deficiency.

Treatment (depending on the symptomatology): measures to prevent further absorption of the drug,increased renal excretion by forced diuresis (alkalinization of urine contributes to the excretion of sulfamethoxazole), hemodialysis (peritoneal dialysis is ineffective). It is necessary to control the picture of blood and electrolytes. At the expressed pathological changes of a picture of a blood or an icterus appoint specific treatment. To eliminate the effect of trimethoprim on hematopoiesis, calcium folinate can be given at a dose of 3-6 mg IM for 5-7 days.

Interaction:

In elderly and senile patients who simultaneously took certain diuretics (mainly thiazides), an increased incidence of thrombocytopenia was observed. Bactrim® can increase serum concentrations of digoxin, especially in elderly patients, therefore, monitoring serum digoxin concentrations is necessary. Bactrim® can enhance the anticoagulant effect of warfarin. ABOUT The possibility of such interaction should be remembered when appointing Bactrim® patients who are already receiving anticoagulants. In such cases, the blood clotting time must be re-determined.

Bactrim® can inhibit the hepatic metabolism of phenytoin. After the appointment of Bactrim® in usual clinical doses, an increase in the half-life of phenytoin by 39% and a decrease in the rate of its metabolic clearance by 27% were observed. With the simultaneous administration of both drugs, it is important to monitor the toxic effects of phenytoin.

In patients receiving trimethoprim-sulfamethoxazole and ciclosporin after a kidney transplant, there may be a reversible impairment of kidney function, manifested by an increase in the level of creatinine. Probably, this effect is caused by trimethoprim. Patients with normal renal function had a reversible decrease in creatinine clearance, which may be due to reversible inhibition of tubular creatinine secretion.

Bactrim® can reduce the effectiveness of tricyclic antidepressants. Sulfonamides, including sulfamethoxazole, can compete for protein binding and renal transport of methotrexate, thereby increasing the concentration of free methotrexate and its systemic effect.

In patients taking trimethoprim and methotrexate, cases of pancytopenia have been described. Trimethoprim has a low affinity for human dehydrofolate reductase, but it can increase the toxicity of methotrexate, especially in the presence of others risk factors such as old age, hypoalbuminemia, impaired renal function, bone marrow depression. Such side reactions are more likely if methotrexate appoint in large doses. For the prevention of myelosuppression, it is recommended that folic acid or folinate calcium should be administered to such patients.

It can be assumed that with the simultaneous appointment of Bactrim® patients who receive pyrimethamine for the prevention of malaria in doses of more than 25 mg per week, they can develop megaloblastic anemia.

Like other sulfonamides, Bactrim can potentiate the effect of oral hypoglycemic drugs.

Trimethoprim, by inhibiting the kidney transport system, increases the area under the concentration-time curve AUC by 103% and the maximum concentration by 93% of dofetilide. With an increase in concentration, dofetilide can cause severe ventricular arrhythmias with lengthening of the interval QT, including arrhythmia torsades de pointes. The simultaneous administration of dofetilide and trimethoprim is contraindicated.

In patients receiving indomethacin, the concentration of sulfamethoxazole in the blood can increase.

One case of toxic delirium is described after simultaneous administration of trimethoprim-sulfamethoxazole and amantadine.

Laboratory research

Bactrim® and, in particular, the trimethoprim included in its composition may affect the results of determination of serum methotrexate concentration, conducted by competitive binding with proteins using bacterial dihydrofolate reductase as a ligand. However, there is no interference with methotrexate by the radioimmune method.

Trimethoprim and sulfamethoxazole may also affect the results of the Jaffe reaction (determination of creatinine by reaction with picric acid in an alkaline medium), while in the range of normal values the results are overestimated by about 10%.

Special instructions:At the first appearance of a skin rash or any other serious adverse reaction the drug should be discarded. Patients with a tendency to allergic reactions and with bronchial asthma drug Bactrim® should be administered with caution.

In elderly and senile patients, as well as in patients with concomitant diseases, for example, impaired renal and / or liver function,or with the simultaneous administration of other drugs, there is an increased risk of serious adverse reactions, the extent of which depends on the dose and duration of therapy. There have been reports of lethal outcomes, although rare, associated with such adverse reactions as blood dyscrasia, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), drug rash with eosinophilia and systemic manifestations (DRESS syndrome), and fulminant necrosis of the liver.

The duration of treatment with Bactrim® should be as short as possible, especially in elderly and senile patients. If the kidney is damaged, the dose should be adjusted according to the instructions in the section "Dosing in special cases". With the long-term administration of Bactrim®, the number of blood cells must be regularly determined. With a significant reduction in the number of any blood cells, Bactrim® should be discarded. Patients with severe hematologic diseases Bactrim® can be assigned only as an exception.
In elderly and senile patients, as well as in patients with an existing deficiency of folic acid or renal insufficiency,hematologic changes, characteristic of a deficiency of folic acid, may occur. They disappear after the administration of folic acid. Patients receiving long-term treatment with Bac-grim® (especially with kidney failure) should regularly make a general urine test and monitor kidney function. During treatment, you need to ensure a sufficient supply of fluid in the body and adequate diuresis to prevent crystalluria.

Because of the possibility of hemolysis, the drug BuckTrim® can be administered to patients with a deficiencyvolume of glucose-6-phosphate dehydrogenase only in absolute indications and in minimum doses.

Trimethoprim disrupts the exchange of phenylalanine, but this does not affect patients with phenylketonuria, provided that the appropriate diet is observed.

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

Patients, whose metabolism is characterized by "slow acetylation," are more prone to the development of idiosyncrasy to sulfonamides.

Form release / dosage:

Suspension for oral administration 240 mg / 5 ml.

Packaging:

To 50 ml or 100 ml of the preparation in bottles of brown glass with a screw cap made of polypropylene, with the control of the first opening.

1 bottle with instructions for use and a measuring spoon is placed in a cardboard box.

Storage conditions:At temperatures not higher than 30 ° C, out of reach of children.

Shelf life:

5 years. The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014160 / 01

Date of registration:29.09.2008

The owner of the registration certificate:Hoffmann-La Roche Ltd.Hoffmann-La Roche Ltd. Switzerland

Manufacturer: & nbsp

CENEXI, SAS France

Representation: & nbspF.Hoffmann-La Roche Ltd. F.Hoffmann-La Roche Ltd. Switzerland

Information update date: & nbsp02.04.2013

Illustrated instructions

Instructions

Bactrim® (Bactrim® )