Bactrim

Generic Name: sulfamethoxazole and trimethoprim (sul fa meth OX a zole and trye METH oh prim)
Brand Names: Bactrim DS, Septra, Septra DS, SMZ-TMP DS, Sulfatrim Pediatric

Dosage form
Film-coated tablets

Composition

One tablet, film coated contains:

Active ingredients:

co-trimoxazole 960 mg

(Equivalent to 800 mg sulfamethoxazole and 160 mg trimethoprim);

Other ingredients: povidone, sodium starch glycolate (sodium carboxymethyl starch), magnesium stearate, sodium docusate;

shell: hydroxypropyl methylcellulose (hypromellose), talc, titanium dioxide, polyethylene glycol 6000 (macrogol).

Description

Oblong, biconvex tablets, coated in white or nearly white, with an engraving on one side «ROCHE 800 160" and the break line on the other side, without odor or with mild odor.
Length tablets 18.7 - 19.8 mm, width 8.5 - 9.4 mm, thickness 6.7 - 8.0 mm.

Pharmacotherapeutic group

Combined antimicrobial agent
ATC code [J01EE01]

Pharmacological action

Pharmacodynamics

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

In vitro antibacterial effects of Bactrim covers a broad spectrum of gram-positive and Gram-negative pathogens, although the sensitivity may depend on geographic location.

Usually susceptible (MIC <80 mg / L for sulfamethoxazole)

Cocci: Branhamella catarrhalis.

Gram-negative microorganisms: Haemophilus influenzae (b-and b-laktamazoobrazuyuschie laktamazoneobrazuyuschie strains), Haemophilus parainfluenzae, E. 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 types of Serratia, Proteus mirabilis, Proteus vulgaris, Morganella morganii,, Shigella spp ., Yersinia enterocolitica, other species of Yersinia, Vibrio cholerae.

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

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

Partially susceptible (MIC = 80-160 mg / L for sulfamethoxazole)

Cocci: Staphylococcus aureus (metitsillinochuvstvitelnye and metitsillinoustoychivye strains), Staphylococcus spp. (Coagulase), Streptococcus pneumoniae (penitsillinochuvstvitelnye and penitsillinoustoychivye strains).

Gram-negative bacillus: Haemophilus ducreyi, Providentia rettgeri, other Providentia, Salmonella typhi, Salmonella enteritidis, Stenotrophomonas maltophilia (formerly Xanthomonas maltophilia).

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

Strains 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 pathogens specific infectious disease.

Infections, which may be caused partially susceptible organisms, it is recommended to test for sensitivity to rule out resistance of the parasite.

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

Pharmacokinetics

Suction

After oral administration of trimethoprim and sulfamethoxazole is rapidly and almost completely absorbed in the upper gastrointestinal tract. After 1-4 h after a single dose of 160 mg trimethoprim + 800 mg sulfamethoxazole trimethoprim maximum concentration in plasma is 1.5-3 mcg / ml and sulfamethoxazole - 40-80 mg / ml. When multiple reception with interval of 12 hours minimum equilibrium concentrations of 2-3 days will stabilize within the 1.3-2.8 mg / ml for trimethoprim and 32-63 micrograms / ml for sulfamethoxazole.

Distribution

The volume of distribution of trimethoprim is about 130 liters, sulfamethoxazole - about 20 liters. 45% of trimethoprim and sulfamethoxazole 66% associated with plasma proteins.

Trimethoprim slightly better than sulfamethoxazole penetrates nevospalennuyu prostate tissue, seminal fluid, the secret vagina, saliva, healthy and inflamed lung tissue, bile, while in the cerebrospinal fluid and aqueous humor eye both components of the drug penetrate the same.

Large amounts of trimethoprim and sulfamethoxazole several smaller amounts coming from the bloodstream into interstitial extravasal and other body fluids, with concentrations of trimethoprim and sulfamethoxazole exceeds the minimum inhibitory concentration for most pathogens.

In humans, trimethoprim and sulfamethoxazole are found in the placenta, umbilical cord blood, amniotic fluid and fetal tissues (liver, lungs), which indicates that both the penetration of substances across the placental barrier. Typically, the concentration of trimethoprim in the fetus close 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. Concentration in breast milk are similar (trimethoprim) or below (SMX), those in the plasma of the mother.

Metabolism

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

Breeding

Half-lives of the two components are very close to each other (on average 10 hours for trimethoprim and 11 hours for sulfamethoxazole).

Both compounds and their metabolites are derived almost exclusively through the kidneys through both glomerular filtration and tubular secretion, resulting in concentrations of both active substances in the urine is 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 with severe renal insufficiency (creatinine clearance 15-30 ml / min), half-lives of both components of the product increases, which require dose adjustment.

Statement

Bactrim should be prescribed only in cases where, according to the physician, the benefit of such therapy outweighs the potential risk, should address the question of whether you can get by using a single effective antibacterial agent.

Since the sensitivity of bacteria to antibiotics in vitro varies in different geographical areas and over time, the choice of the drug should take into account local features of bacterial sensitivity.

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

Urinary tract infection: urinary tract infection, chancroid.

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

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

Contraindications

Pronounced lesions in the liver parenchyma, severe renal impairment (creatinine clearance <15 ml / min), if you can not routinely determine the drug concentration in plasma, blood disorders (aplastic anemia, B12 deficiency anemia, agranulocytosis, leukopenia), hypersensitivity to the drug history and in combination with dofetilidom; children under the age of 12 years, lack of glucose-6-phosphate dehydrogenase.

Precautions

Porphyria, impaired thyroid function, asthma, folic acid deficiency.

Pregnancy and lactation

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

According to studies in pregnant women, literary reviews and some posts about the evils of taking Bactrim, apparently, does not involve significant risk of teratogenicity in humans.

Since both trimethoprim and sulfamethoxazole pass through the placental barrier and thus may affect the exchange of folic acid during pregnancy Bactrim should be given only if the expected benefits from its use outweigh the risks to the fetus. Pregnant women receiving Bactrim, recommended to prescribe 5 mg of folic acid per day. In late pregnancy should be avoided Bactrim because of the possible risk of kernicterus in newborns.

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

Dosing and Administration

Inside, after a meal with plenty of fluids.

Standard dosing

Adults and children older than 12 years:

Duration of treatment

In acute infections, Bactrim should be appointed for a term of not less than 5 days or until symptoms until the patient will be absent 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.

Dosing in special cases

Chancroid

1 tablet twice a day. If after 7 days of healing of skin element does not occur, it is possible to extend treatment for another 7 days. However, it should be borne in mind that the lack of effect may indicate a resistance of the parasite.

Acute uncomplicated urinary tract infections

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

Patients on hemodialysis

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

Pneumonia caused by Pneumocystis carinii

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

For the prevention of pneumonia caused by Pneumocystis carinii, adults and adolescents (under 12 years) are encouraged to nominate 1 tablet per day. In children, for the prevention of pneumonia caused by Pneumocystis carinii, should use a different dosage form of the drug Bactrim - a suspension for oral administration. Nokardioz

Adults 3-4 tablets for at least 3 months. The dose should be adjusted depending on age, patient weight, renal function and disease severity. Sometimes the treatment is continued until 18 months.

Patients with impaired renal function

If creatinine clearance> 30 ml / min prescribed the usual dose, when creatinine clearance 15-30 ml / minute - half the usual dose, while creatinine clearance <15 ml / min apply Bactrim is not recommended.

Elderly patients

With normal renal function appoint the usual dose for adults.

Side effect

In the recommended doses of Bactrim is usually well tolerated. The most common side effects are skin rash and gastrointestinal disorders.

Organism as a whole

Described hypersensitivity reactions. As with any other drug treatment in patients with hypersensitivity to the drug may develop an allergic reaction: fever, angioedema, anaphylactoid reactions, serum sickness, in rare cases - pulmonary infiltrates on the type of eosinophilic or allergic alveolitis. They may be clinically manifested by coughing and shortness of breath. With the sudden appearance or increase in such symptoms the patient should be evaluated and to consider the termination of therapy Bactrim. In rare cases, there periarteritis nodosa and allergic myocarditis. There are cases of fungal infections such as candidiasis.

In descending order of frequency may experience the following side effects.

Skin: The adverse reactions usually are mild and disappear rapidly after discontinuation of the drug. Like other medications containing sulfonamides, Bactrim, in rare cases can lead to photosensitization, development of erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome) and purple-Schonlein purpura.

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

Hematological changes: leukopenia, neutropenia, granulocytopenia and thrombocytopenia (often expressed poorly or are asymptomatic and disappear after drug withdrawal) is very rare - agranulocytosis, anemia (megaloblastic, hemolytic / or autoimmune aplastic), methemoglobinemia, pancytopenia and purpura.

Urinary tract: in rare cases - renal dysfunction, interstitial nephritis, increased blood urea nitrogen, serum creatinine, crystalluria. Sulfonamides, including Bactrim, can lead to an increase in urine output, especially in patients with edema of cardiac origin.

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

Respiratory system: individual cases of pulmonary infiltrates, such as those that arise in eosinophilic or allergic alveolitis. They may show symptoms such as cough or shortness of breath. With the sudden appearance or increase of the symptoms need to re-examine the patient and consider discontinuing treatment Bactrim.

Musculoskeletal system: rarely - arthralgia, and myalgia are described isolated cases of rhabdomyolysis.

Metabolism: high-dose trimethoprim used to treat Pneumocystis carinii pneumonia, leading to a progressive, but reversible increases in serum potassium in a significant number of patients. Hyperkalaemia can cause

even taking the recommended dose of trimethoprim, if it is prescribed on a background of violations

potassium metabolism, kidney failure, or simultaneous use of the drugs that provoke hyperkalemia. These patients need to regularly monitor the content of potassium in serum. There are cases of hyponatremia. Persons who are not suffering from diabetes and receiving trimethoprim-sulfamethoxazole, and occasionally there are cases of hypoglycemia, usually within a few days after starting 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 frequency of side effects, particularly rash, fever, leukopenia and elevated aminotransferase activity in serum of patients with AIDS, is significantly higher than those in patients not suffering from AIDS.

Overdose

Symptoms of acute overdose: Nausea, vomiting, diarrhea, headache, dizziness, intellectual and visual disturbances, in severe cases - crystalluria, hematuria, and anuria.

Symptoms of chronic overdose: inhibition of blood (thrombocytopenia, 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, increased renal excretion through forced diuresis (urine alkalinization promotes the excretion of sulfamethoxazole), hemodialysis (peritoneal dialysis is ineffective). Necessary to control the blood picture and electrolytes. When expressed in pathological changes in the blood picture or prescribe specific treatment for jaundice. To eliminate the action of trimethoprim on hematopoiesis may be given calcium folinate at a dose of 3-6 mg / m within 5-7 days.

Interaction with other drugs

In patients with middle and old age, while taking some diuretics (mainly thiazides), we observed an increased frequency of thrombocytopenia.

Cautions

Expiration date

Storage conditions

Prescription.