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

shell: hydroxypropylmethylcellulose (hypromellose) - 6.5 mg, talc - 3.75 mg, titanium dioxide - 3.75 mg, polyethylene glycol 6000 (macrogol) - 1 mg.

Description:

Oblong, biconvex tablets, coated, white or almost white, engraved on one side "ROCHE 800 + 160 "and the separation risk on the other side, odorless or with a faint smell.

The length of the tablet is 18.7 - 19.8 mm, width 8.5 - 9.4 mm, thickness 6.7 - 8.0 mm.

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. PomiThis, Bactrim®, is often effective against pathogens resistant to one of its components. In vitro The antibacterial effect of Bactrim® encompasses a wide range of gram-positive and gram-negative pathogens, although sensitivity may depend on 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, Citrobacter freundii, other types Citrobacter, Klebsiella pneumoniae, Klebsiella oxytoca, other types Klebsiella, Enterobacter cloaceae, Enterobacter aerogenes, Hafnia alvei, Serratia marcescens, Serratis liquefaciens, other types Serratia, Proteus mirabilis, Proteus vulgaris, Morganella morgani,, Shigella spp., Yersinia enterocolitica, other types Yersinia, Vibrio cholerae.

Different gram negative microorganismsare: Edwardsiella tarda, Alcalisenes faecalis, Pseudomonas cepacia, Burkholderia (Pseudomonas) pseudomallei.

Clinical experience shows that sensitive can be and Brucella spp., Listeria monocytogenes, Nocar dia 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 rods: Haemophilus ducreyi, Providentia rettgeri, other types Providentia, Salmonella typhi, Salmonella enter hi dis, Stenotrophomonas maltophilia (previously called Xanthomonas maltophilia).

Different gram-negative microorganisms: Acinetobacter Iwoffi, Acinetobacter anitratus (mainly A. baumanii), Aeromonas hydrophilia.

Stable pathogens (MIC> 160 mg / L on sulfamethoxazole)

Mycoplasma spp., Mycobacterium tuberculosis, Treponema pallidum.

If Bactrim® is administered empirically, local characteristics of Bactrim® resistance to possible pathogens of a specific infectious disease must be considered.

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. The sensitivity to Bactrim® can be determined by standard methods, for example, by disk or dilution methods recommended by the National Committee for Clinical Laboratory Standards (NCCLC).The BCC recommends the following criteria sensitivity:

	Method disks *,	The breeding method **, MIC (μg / ml)
	diameter of the growth inhibition zone (mm)	trimetoprim	sulnotesSazole
Sensationsthe	≥16	≤2	≤38
Partially sensitivethe	11-15	4	76
Steadythe	≤10	≥8	≥152

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

** Trimethoprim and sulfamethoxazole 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. After 1-4 hours after a single dose 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. At repeated reception with an interval of 12 hours minimum are equalspring concentrations after 2-3 days of stabilitylysed within 1.3-2.8 μg / ml for trimethoprim 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, both in the cerebrospinal fluid and watery eyes, both components of the drug penetrate equally.

Large amounts of trimethoprim and slightly smaller amounts of sulfamethoxazole come from the bloodstream into the interstitial and other extravasal body fluids,while the concentrations of trimethoprim and sulfamethoxazole exceed the minimum inhibitory concentrations for most pathogenic microorganisms.

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

Half-life of two componentsare very close to each other (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 much 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 are increased, 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. Since the sensitivity of bacteria to antibiotics in vitro varies in different geographical areas and in time, when selecting 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 basispreferring a combination of trimethoprim and sulfamethoxazole monotherapy with an antibiotic. Treatment and prevention (primary and secondary) of pneumonia caused by Pneumocystis carinii, in 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; children's age till 12 years; deficiency of glucose-6-phosphate dehydrogenase.

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

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, I getBactrim®, it is recommended to appoint 5 mg of folic acid per day. In late pregnancy, Bactrim should be avoided because of the possible risk of nuclear jaundice in newborns.

Both trimethoprim and sulfamethoxazole penetrate into breast milk.In spite of the fact that small amounts of Bactrim get to the baby with breast milk, it is recommended to compare the possible risk for the 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

Adults and children over 12 years of age:

	Film-coated tablets
	morning	evening
Standard dose	1	1
The minimum dose and dose for long-term treatment (more than 14 days)	0.5	0.5
Increased dose (in particularly severe cases)	1.5	1.5

Duration 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

1 tablet twice a day. If the skin does not heal after 7 days, you can extend the therapy 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 recommend a one-time intake of 2-3 tablets. 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 afterthe following table:

Body weight, kg	Doses taken at 6-hour intervals, coated tablets
32	1
40
48	1.5
64	2
80	2.5

For the prevention of pneumonia caused by Pneumocystis carinii, Adults and adolescents (over 12 years of age) are recommended to take 1 tablet a day. In children for the prevention of pneumonia caused by Pneumocystis carinii, Use another dosage form of the preparation Bakgrim ® - suspension for oral administration.

Nocardiosis

Adults 3-4 tablets 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

In case of creatinine clearance> 30 ml / min prescribe the usual dose, with clearancecreatinine 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.

On the part of the body as a whole. Hypersensitivity reactions 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. With the sudden appearance or increase of such symptoms, the patient should be examined and consider stopping therapy with 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, a drug rash with eosinophilia and systemic manifestations (DRESS syndrome). From the gastrointestinal tract: nausea (with vomiting or without), stomatitis, diarrhea, liver necrosis, rare cases of gepatita, 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. Sulfonamides, 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, 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 to treat PCP cause Progressive, but reversiblepotassium content in serum 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 regular monitoring the content of potassium in the serum. Cases of hyponatremia are described. People who do not have diabetes and receive trimethoprim-sulfamethoxazole occasionally experience cases of hypoglycemia, usually a few days after the start of 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 side effects, especially rash, fever,leukopenia and increased activity of hepatic aminotransferases in serum in AIDS patients is significantly higher than that of 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 yellowhe appoint a 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. The possibility of such interaction should be remembered in the appointment of Bactrim to 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 other risk factors, such as senile age, hypoalbuminemia, renal dysfunction, 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 to 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, maylick concentration of sulfamethoxazole in the blood.

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 dermal rash or any other severe adverse reaction drug should be discarded. Patients with a tendency to allergic reactions and with bronchial asthma preparation Bactrim® should be administered with caution.
Have elderly patients, as well as patients with concomitant diseases, for example, renal and / or liver dysfunction, or with 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. In case of kidney damage, 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 prescribed 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 folic acid deficiency, may occur. They disappear after the administration of folic acid.

Patients receiving long-term treatment with Bactrim® (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, Bactrim® can be administered to patients with glucose-6-phosphate dehydrogenase deficiency only in absolute indications and in minimal 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:

Tablets coated with a coating, 960 mg.

Packaging:

For 10 tablets in a blister of PVC film and aluminum foil.

For 1, 2 or 5 blisters together with the instructions for use are 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 N014158 / 01

Date of registration:12.09.2008

Date of cancellation:2017-01-09

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

Manufacturer: & nbsp

F.Hoffmann-La Roche, Ltd. Switzerland

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

Information update date: & nbsp15.01.2017

Illustrated instructions

Instructions

Bactrim® forte (Bactrim® forte)