قرص trimethoprim - کامل (هلپ کده)

خواص دارویی و گیاهی

Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections.[1] Other uses include for middle ear infections and travelers’ diarrhea.[1] With sulfamethoxazole or dapsone it may be used for Pneumocystis pneumonia in people with HIV/AIDS.[1][2] It is taken by mouth.[1]

Common side effects include nausea, changes in taste, and rash.[1] Rarely it may result in blood problems such as not enough platelets or white blood cells.[1] May cause sun sensitivity.[1] There is evidence of potential harm during pregnancy in some animals but not humans.[3] It works by blocking folate metabolism via dihydrofolate reductase in some bacteria which results in their death.[1]

Trimethoprim was first used in 1962.[4] It is on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system.[5] It is available as a generic medication and is not very expensive.[6] In the United States, ten days of treatment costs about $21.[1]

It is primarily used in the treatment of urinary tract infections, although it may be used against any susceptible aerobic bacterial species.[7] It may also be used to treat and prevent Pneumocystis jirovecii pneumonia.[7] It is generally not recommended for the treatment of anaerobic infections such as Clostridium difficile colitis (the leading cause of antibiotic-induced diarrhea).[7] Trimethoprim has been used in trials to treat retinitis.[8]

Resistance to trimethoprim is increasing, but it is still a first line antibiotic in many countries.[9]
قرص trimethoprim

Cultures and susceptibility tests should be done to make sure bacteria is treated by trimethoprim.[10][11]

10-20% of trimethoprim is metabolized by the liver and the rest is excreted in the urine. Therefore, trimethoprim should be used with caution in individuals with kidney and liver impairments. Dosage adjustment is not needed for liver impairment but should be adjusted for kidney impairment.[19]

Based on studies that show that trimethoprim crosses the placenta and can affect folate metabolism, there has been growing evidence of the risk of structural birth defects associated with trimethoprim, especially during the first trimester of pregnancy.[20] It may be involved in a reaction similar to disulfiram when alcohol is consumed after it is used, in particular when used in combination with sulfamethoxazole.[21][22]
The trophoblasts in the early fetus are sensitive to changes in the folate cycle. A recent study has found a doubling in the risk of miscarriage in women exposed to trimethoprim in the early pregnancy.[23]

Trimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF).[25] THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis.[25] Trimethoprim’s affinity for bacterial dihydrofolate reductase is several thousand times greater than its affinity for human dihydrofolate reductase.[25] Sulfamethoxazole inhibits dihydropteroate synthase, an enzyme involved further upstream in the same pathway.[25] Trimethoprim and sulfamethoxazole are commonly used in combination due to possible synergistic effects, and reduced development of resistance.[25] This benefit has been questioned.[26]

Trimethoprim was first used in 1962.[4] In 1972, it was used as a prophylactic treatment for urinary tract infections in Finland.[4]

The liver is an organ only found in vertebrates which detoxifies various metabolites, synthesizes proteins and produces biochemicals necessary for digestion.[2][3][4] In humans, it is located in the right upper quadrant of the abdomen, below the diaphragm. Its other roles in metabolism include the regulation of glycogen storage, decomposition of red blood cells and the production of hormones.[4]

The liver is an accessory digestive gland that produces bile, an alkaline compound which helps the breakdown of fat. Bile aids in digestion via the emulsification of lipids. The gallbladder, a small pouch that sits just under the liver, stores bile produced by the liver which is afterwards moved to the small intestine to complete digestion.[5] The liver’s highly specialized tissue consisting of mostly hepatocytes regulates a wide variety of high-volume biochemical reactions, including the synthesis and breakdown of small and complex molecules, many of which are necessary for normal vital functions.[6] Estimates regarding the organ’s total number of functions vary, but textbooks generally cite it being around 500.[7]

Terminology related to the liver often starts in hepat- from ἡπατο-, from the Greek word for liver.[8]

No way is yet known to compensate for the absence of liver function in the long term, although liver dialysis techniques can be used in the short term. Artificial livers are yet to be developed to promote long-term replacement in the absence of the liver. As of 2018[update],[9] liver transplantation is the only option for complete liver failure.

The liver is a reddish-brown, wedge-shaped organ with four lobes of unequal size and shape. A human liver normally weighs approximately 1.5 kg (3.3 lb),[10] and has a width of about 15 cm (6 in).[11] It is both the heaviest internal organ and the largest gland in the human body.
Located in the right upper quadrant of the abdominal cavity, it rests just below the diaphragm, to the right of the stomach and overlies the gallbladder.[5]
قرص trimethoprim

The liver is connected to two large blood vessels: the hepatic artery and the portal vein and common hepatic duct. The hepatic artery carries oxygen-rich blood from the aorta via the celiac plexus, whereas the portal vein carries blood rich in digested nutrients from the entire gastrointestinal tract and also from the spleen and pancreas.[9] These blood vessels subdivide into small capillaries known as liver sinusoids, which then lead to lobules.

Lobules are the functional units of the liver. Each lobule is made up of millions of hepatic cells (hepatocytes), which are the basic metabolic cells. The lobules are held together by a fine, dense, irregular, fibroelastic connective tissue layer which extends from the fibrous capsule covering the entire liver known as Glisson’s capsule.[4] This extends into the structure of the liver, by accompanying the blood vessels (veins and arteries), ducts, and nerves at the hepatic hilum. The whole surface of the liver except for the bare area, is covered in a serous coat derived from the peritoneum, and this firmly adheres to the inner Glisson’s capsule.

The liver is grossly divided into two parts when viewed from above – a right and a left lobe, and four parts when viewed from below (left, right, caudate, and quadrate lobes).[12]

The falciform ligament divides the liver into a left and right lobe. From below, the two additional lobes are located between the right and left lobes, one in front of the other. A line can be imagined running from the left of the vena cava and all the way forward to divide the liver and gallbladder into two halves.[13] This line is called “Cantlie’s line”.[14]

Other anatomical landmarks include the ligamentum venosum and the round ligament of the liver (ligamentum teres), which further divide the left side of the liver in two sections. An important anatomical landmark, the porta hepatis, divides this left portion into four segments, which can be numbered starting at the caudate lobe as I in an anticlockwise manner. From this parietal view, seven segments can be seen, because the eighth segment is only visible in the visceral view.[15]

On the diaphragmatic surface, apart from a triangular bare area where it connects to the diaphragm, the liver is covered by a thin, double-layered membrane, the peritoneum, that helps to reduce friction against other organs.[16] This surface covers the convex shape of the two lobes where it accommodates the shape of the diaphragm. The peritoneum folds back on itself to form the falciform ligament and the right and left triangular ligaments.[17]

These peritoneal ligaments are not related to the anatomic ligaments in joints, and the right and left triangular ligaments have no known functional importance, though they serve as surface landmarks.[17] The falciform ligament functions to attach the liver to the posterior portion of the anterior body wall.

The visceral surface or inferior surface, is uneven and concave. It is covered in peritoneum apart from where it attaches the gallbladder and the porta hepatis.[16] The fossa of gall bladder lies to the right of the quadrate lobe,occupied by the gallbladder with its cystic duct close to the right end of porta hepatis.

Several impressions on the surface of the liver accommodate the various adjacent structures and organs. Underneath the right lobe and to the right of the gallbladder fossa are two impressions, one behind the other and separated by a ridge. The one in front is a shallow colic impression, formed by the hepatic flexure and the one behind is a deeper renal impression accommodating part of the right kidney and part of the suprarenal gland.[18]

The suprarenal impression is a small, triangular, depressed area on the liver. It is located close to the right of the fossa, between the bare area and the caudate lobe, and immediately above the renal impression. The greater part of the suprarenal impression is devoid of peritoneum and it lodges the right suprarenal gland.[19]

Medial to the renal impression is a third and slightly marked impression, lying between it and the neck of the gall bladder. This is caused by the descending portion of the duodenum, and is known as the duodenal impression.[19]

The inferior surface of the left lobe of the liver presents behind and to the left the gastric impression.[19] This is moulded over the upper front surface of the stomach, and to the right of this is a rounded eminence, the tuber omentale, which fits into the concavity of the lesser curvature of the stomach and lies in front of the anterior layer of the lesser omentum.

Microscopically, each liver lobe is seen to be made up of hepatic lobules. The lobules are roughly hexagonal, and consist of plates of hepatocytes radiating from a central vein.[20][page needed]The central vein joins to the hepatic vein to carry blood out from the liver. A distinctive component of a lobule is the portal triad, which can be found running along each of the lobule’s corners. The portal triad, misleadingly named, consists of five structures: a branch of the hepatic artery, a branch of the hepatic portal vein, and a bile duct, as well as lymphatic vessels and a branch of the vagus nerve.[21] Between the hepatocyte plates are liver sinusoids, which are enlarged capillaries through which blood from the hepatic portal vein and hepatic artery enters via the portal triads, then drains to the central vein.[20][page needed]

Histology, the study of microscopic anatomy, shows two major types of liver cell: parenchymal cells and nonparenchymal cells. About 70–85% of the liver volume is occupied by parenchymal hepatocytes. Nonparenchymal cells constitute 40% of the total number of liver cells but only 6.5% of its volume.[22] The liver sinusoids are lined with two types of cell, sinusoidal endothelial cells, and phagocytic Kupffer cells.[23] Hepatic stellate cells are nonparenchymal cells found in the perisinusoidal space, between a sinusoid and a hepatocyte.[22]
Additionally, intrahepatic lymphocytes are often present in the sinusoidal lumen.[22]

The central area or hepatic hilum, includes the opening known as the porta hepatis which carries the common bile duct and common hepatic artery, and the opening for the portal vein. The duct, vein, and artery divide into left and right branches, and the areas of the liver supplied by these branches constitute the functional left and right lobes. The functional lobes are separated by the imaginary plane, Cantlie’s line, joining the gallbladder fossa to the inferior vena cava. The plane separates the liver into the true right and left lobes. The middle hepatic vein also demarcates the true right and left lobes. The right lobe is further divided into an anterior and posterior segment by the right hepatic vein. The left lobe is divided into the medial and lateral segments by the left hepatic vein.

The hilum of the liver is described in terms of three plates that contain the bile ducts and blood vessels. The contents of the whole plate system are surrounded by a sheath.[24] The three plates are the hilar plate, the cystic plate and the umbilical plate and the plate system is the site of the many anatomical variations to be found in the liver.[24]

In the widely used Couinaud system, the functional lobes are further divided into a total of eight subsegments based on a transverse plane through the bifurcation of the main portal vein.[25] The caudate lobe is a separate structure that receives blood flow from both the right- and left-sided vascular branches.[26][27] The Couinaud classification of liver anatomy divides the liver into eight functionally independent liver segments. Each segment has its own vascular inflow, outflow and biliary drainage. In the centre of each segment are branches of the portal vein, hepatic artery, and bile duct. In the periphery of each segment is vascular outflow through the hepatic veins.[28] The classification system uses the vascular supply in the liver to separate the functional units (numbered I to VIII), with unit 1, the caudate lobe, receiving its supply from both the right and the left branches of portal vein. It contains one or more hepatic veins which drain directly into the inferior vena cava.[25] The remainder of the units (II to VIII) are numbered in a clockwise fashion:[28]

About 20,000 protein coding genes are expressed in human cells and 60% of these genes are expressed in a normal, adult liver.[29][30] Over 400 genes are more specifically expressed in the liver, with some 150 genes highly specific for liver tissue. A large fraction of the corresponding liver specific proteins are mainly expressed in hepatocytes and secreted into the blood and constitute plasma proteins. Other liver specific proteins are certain liver enzymes such as HAO1 and RDH16, proteins involved in bile synthesis such as BAAT and SLC27A5, and transporter proteins involved in the metabolism of drugs, such as ABCB11 and SLC2A2. Examples of highly liver-specific proteins include apolipoprotein A II, coagulation factors F2 and F9, complement factor related proteins, and the fibrinogen beta chain protein.[31]

Organogenesis, the development of the organs takes place from the third to the eighth week during embryogenesis. The origins of the liver lie in both the ventral portion of the foregut endoderm (endoderm being one of the three embryonic germ layers) and the constituents of the adjacent septum transversum mesenchyme. In the human embryo, the hepatic diverticulum is the tube of endoderm that extends out from the foregut into the surrounding mesenchyme. The mesenchyme of septum transversum induces this endoderm to proliferate, to branch, and to form the glandular epithelium of the liver. A portion of the hepatic diverticulum (that region closest to the digestive tube) continues to function as the drainage duct of the liver, and a branch from this duct produces the gallbladder.[32] Besides signals from the septum transversum mesenchyme, fibroblast growth factor from the developing heart also contributes to hepatic competence, along with retinoic acid emanating from the lateral plate mesoderm. The hepatic endodermal cells undergo a morphological transition from columnar to pseudostratified resulting in thickening into the early liver bud. Their expansion forms a population of the bipotential hepatoblasts.[33] Hepatic stellate cells are derived from mesenchyme.[34]

After migration of hepatoblasts into the septum transversum mesenchyme, the hepatic architecture begins to be established, with liver sinusoids and bile canaliculi appearing. The liver bud separates into the lobes. The left umbilical vein becomes the ductus venosus and the right vitelline vein becomes the portal vein. The expanding liver bud is colonized by hematopoietic cells. The bipotential hepatoblasts begin differentiating into biliary epithelial cells and hepatocytes. The biliary epithelial cells differentiate from hepatoblasts around portal veins, first producing a monolayer, and then a bilayer of cuboidal cells. In ductal plate, focal dilations emerge at points in the bilayer, become surrounded by portal mesenchyme, and undergo tubulogenesis into intrahepatic bile ducts. Hepatoblasts not adjacent to portal veins instead differentiate into hepatocytes and arrange into cords lined by sinudoidal epithelial cells and bile canaliculi. Once hepatoblasts are specified into hepatocytes and undergo further expansion, they begin acquiring the functions of a mature hepatocyte, and eventually mature hepatocytes appear as highly polarized epithelial cells with abundant glycogen accumulation. In the adult liver, hepatocytes are not equivalent, with position along the portocentrovenular axis within a liver lobule dictating expression of metabolic genes involved in drug metabolism, carbohydrate metabolism, ammonia detoxification, and bile production and secretion. WNT/β-catenin has now been identified to be playing a key role in this phenomenon.[33]

At birth, the liver comprises roughly 4% of body weight and weighs on average about 120 g (4 oz). Over the course of further development, it will increase to 1.4–1.6 kg (3.1–3.5 lb) but will only take up 2.5–3.5% of body weight.[35]

In the growing fetus, a major source of blood to the liver is the umbilical vein, which supplies nutrients to the growing fetus. The umbilical vein enters the abdomen at the umbilicus and passes upward along the free margin of the falciform ligament of the liver to the inferior surface of the liver. There, it joins with the left branch of the portal vein. The ductus venosus carries blood from the left portal vein to the left hepatic vein and then to the inferior vena cava, allowing placental blood to bypass the liver.

In the fetus, the liver does not perform the normal digestive processes and filtration of the infant liver because nutrients are received directly from the mother via the placenta. The fetal liver releases some blood stem cells that migrate to the fetal thymus, creating the T-cells or T-lymphocytes. After birth, the formation of blood stem cells shifts to the red bone marrow.

After 2–5 days, the umbilical vein and ductus venosus are completely obliterated; the former becomes the round ligament of liver and the latter becomes the ligamentum venosum. In the disorders of cirrhosis and portal hypertension, the umbilical vein can open up again.

The various functions of the liver are carried out by the liver cells or hepatocytes. The liver is thought to be responsible for up to 500 separate functions, usually in combination with other systems and organs. Currently, no artificial organ or device is capable of reproducing all the functions of the liver. Some functions can be carried out by liver dialysis, an experimental treatment for liver failure. The liver also accounts for about 20% of resting total body oxygen consumption.

The liver receives a dual blood supply from the hepatic portal vein and hepatic arteries. The hepatic portal vein delivers around 75% of the liver’s blood supply, and carries venous blood drained from the spleen, gastrointestinal tract, and its associated organs. The hepatic arteries supply arterial blood to the liver, accounting for the remaining quarter of its blood flow. Oxygen is provided from both sources; about half of the liver’s oxygen demand is met by the hepatic portal vein, and half is met by the hepatic arteries.[36] The hepatic artery also has both alpha- and beta-adrenergic receptors; therefore, flow through the artery is controlled, in part, by the splanchnic nerves of the autonomic nervous system.

Blood flows through the liver sinusoids and empties into the central vein of each lobule. The central veins coalesce into hepatic veins, which leave the liver and drain into the inferior vena cava.[21]

The biliary tract is derived from the branches of the bile ducts. The biliary tract, also known as the biliary tree, is the path by which bile is secreted by the liver then transported to the first part of the small intestine, the duodenum. The bile produced in the liver is collected in bile canaliculi, small grooves between the faces of adjacent hepatocytes. The canaliculi radiate to the edge of the liver lobule, where they merge to form bile ducts. Within the liver, these ducts are termed intrahepatic bile ducts, and once they exit the liver, they are considered extrahepatic. The intrahepatic ducts eventually drain into the right and left hepatic ducts, which exit the liver at the transverse fissure, and merge to form the common hepatic duct. The cystic duct from the gallbladder joins with the common hepatic duct to form the common bile duct.[21] The biliary system and connective tissue is supplied by the hepatic artery alone

Bile either drains directly into the duodenum via the common bile duct, or is temporarily stored in the gallbladder via the cystic duct. The common bile duct and the pancreatic duct enter the second part of the duodenum together at the hepatopancreatic ampulla, also known as the ampulla of Vater.

The liver plays a major role in carbohydrate, protein, amino acid, and lipid metabolism.

The liver performs several roles in carbohydrate metabolism: The liver synthesizes and stores around 100 g of glycogen via glycogenesis, the formation of glycogen from glucose. When needed, the liver releases glucose into the blood by performing glycogenolysis, the breakdown of glycogen into glucose.[37] The liver is also responsible for gluconeogenesis, which is the synthesis of glucose from certain amino acids, lactate, or glycerol. Adipose and liver cells produce glycerol by breakdown of fat, which the liver uses for gluconeogenesis.[37]

The liver is responsible for the mainstay of protein metabolism, synthesis as well as degradation. It is also responsible for a large part of amino acid synthesis. The liver plays a role in the production of clotting factors, as well as red blood cell production. Some of the proteins synthesized by the liver include coagulation factors I (fibrinogen), II (prothrombin), V, VII, VIII, IX, X, XI, factor XII|[XII]], XIII, as well as protein C, protein S and antithrombin. In the first trimester fetus, the liver is the main site of red blood cell production. By the 32nd week of gestation, the bone marrow has almost completely taken over that task. The liver is a major site of production for thrombopoietin, a glycoprotein hormone that regulates the production of platelets by the bone marrow.[38]

The liver plays several roles in lipid metabolism: it performs cholesterol synthesis, lipogenesis, and the production of triglycerides, and a bulk of the body’s lipoproteins are synthesized in the liver.

The liver plays a key role in digestion, as it produces and excretes bile (a yellowish liquid) required for emulsifying fats and help the absorption of vitamin K from the diet. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder.

The liver also produces insulin-like growth factor 1, a polypeptide protein hormone that plays an important role in childhood growth and continues to have anabolic effects in adults.
قرص trimethoprim

The liver is responsible for the breakdown of insulin and other hormones. The liver breaks down bilirubin via glucuronidation, facilitating its excretion into bile.
The liver is responsible for the breakdown and excretion of many waste products. It plays a key role in breaking down or modifying toxic substances (e.g., methylation) and most medicinal products in a process called drug metabolism. This sometimes results in toxication, when the metabolite is more toxic than its precursor. Preferably, the toxins are conjugated to avail excretion in bile or urine. The liver breaks down ammonia into urea as part of the urea cycle, and the urea is excreted in the urine.[20]

The oxidative capacity of the liver decreases with aging and therefore any medications that require oxidation (for instance, benzodiazepines) are more likely to accumulate to toxic levels. However, medications with shorter half-lives, such as lorazepam and oxazepam, are preferred in most cases when benzodiazepines are required in regard to geriatric medicine.

The liver is a vital organ and supports almost every other organ in the body. Because of its strategic location and multidimensional functions, the liver is also prone to many diseases.[40] The bare area of the liver is a site that is vulnerable to the passing of infection from the abdominal cavity to the thoracic cavity.

Hepatitis is a common condition of inflammation of the liver. The most usual cause of this is viral, and the most common of these infections are hepatitis A, B, C, D, and E. Some of these infections are sexually transmitted. Inflammation can also be caused by other viruses in the family Herpesviridae such as the herpes simplex virus. Chronic (rather than acute) infection with hepatitis B virus or hepatitis C virus is the main cause of liver cancer.[41] Globally, about 248 million individuals are chronically infected with HBV (with 843,724 in the U.S.)[42] and 142 million are chronically infected with HCV[43] (with 2.7 million in the U.S.[44]). Globally there are about 114 million and 20 million cases of hepatitis A[43] and hepatitis E[45] respectively, but these generally resolve, and do not become chronic. Hepatitis D virus is a “satellite” of hepatitis B virus (can only infect in the presence of hepatitis B), and co-infects nearly 20 million people with hepatitis B, globally.[46]

Hepatic encephalopathy is caused by an accumulation of toxins in the bloodstream that are normally removed by the liver. This condition can result in coma and can prove fatal.

Other disorders caused by excessive alcohol consumption are grouped under alcoholic liver diseases and these include alcoholic hepatitis, fatty liver, and cirrhosis. Factors contributing to the development of alcoholic liver diseases are not only the quantity and frequency of alcohol consumption, but can also include gender, genetics, and liver insult.

Liver damage can also be caused by drugs, particularly paracetamol and drugs used to treat cancer. A rupture of the liver can be caused by a liver shot used in combat sports.

Budd–Chiari syndrome is a condition caused by blockage of the hepatic veins (including thrombosis) that drain the liver. It presents with the classical triad of abdominal pain, ascites and liver enlargement.[47]

Primary biliary cholangitis is an autoimmune disease of the liver.[48][49] It is marked by slow progressive destruction of the small bile ducts of the liver, with the intralobular ducts (Canals of Hering) affected early in the disease.[50] When these ducts are damaged, bile and other toxins build up in the liver (cholestasis) and over time damages the liver tissue in combination with ongoing immune related damage. This can lead to scarring (fibrosis) and cirrhosis. Cirrhosis increases the resistance to blood flow in the liver, and can result in portal hypertension. Congested anastomoses between the portal venous system and the systemic circulation, can be a subsequent condition.

Many diseases of the liver are accompanied by jaundice caused by increased levels of bilirubin in the system. The bilirubin results from the breakup of the hemoglobin of dead red blood cells; normally, the liver removes bilirubin from the blood and excretes it through bile.

There are also many pediatric liver diseases, including biliary atresia, alpha-1 antitrypsin deficiency, alagille syndrome, progressive familial intrahepatic cholestasis, Langerhans cell histiocytosis and hepatic hemangioma a benign tumour the most common type of liver tumour, thought to be congenital. A genetic disorder causing multiple cysts to form in the liver tissue, usually in later life, and usually asymptomatic, is polycystic liver disease. Diseases that interfere with liver function will lead to derangement of these processes. However, the liver has a great capacity to regenerate and has a large reserve capacity. In most cases, the liver only produces symptoms after extensive damage.

Hepatomegaly refers to an enlarged liver and can be due to many causes. It can be palpated in a liver span measurement.

Liver diseases may be diagnosed by liver function tests–blood tests that can identify various markers. For example, acute-phase reactants are produced by the liver in response to injury or inflammation.

The classic symptoms of liver damage include the following:

The diagnosis of liver disease is made by liver function tests, groups of blood tests, that can readily show the extent of liver damage. If infection is suspected, then other serological tests will be carried out. A physical examination of the liver can only reveal its size and any tenderness, and some form of imaging such as an ultrasound or CT scan may also be needed.[52]
Sometimes a liver biopsy will be necessary, and a tissue sample is taken through a needle inserted into the skin just below the rib cage. This procedure may be helped by a sonographer providing ultrasound guidance to an interventional radiologist.[53]

Axial CT image showing anomalous hepatic veins coursing on the subcapsular anterior surface of the liver.[54]

Maximum intensity projection (MIP) CT image as viewed anteriorly showing the anomalous hepatic veins coursing on the anterior surface of the liver

Lateral MIP view in the same patient

A CT scan in which the liver and portal vein are shown.

The liver is the only human internal organ capable of natural regeneration of lost tissue; as little as 25% of a liver can regenerate into a whole liver.[55] This is, however, not true regeneration but rather compensatory growth in mammals.[56] The lobes that are removed do not regrow and the growth of the liver is a restoration of function, not original form. This contrasts with true regeneration where both original function and form are restored. In some other species, such as fish, the liver undergoes true regeneration by restoring both shape and size of the organ.[57] In the liver, large areas of the tissues are formed but for the formation of new cells there must be sufficient amount of material so the circulation of the blood becomes more active.[58]

This is predominantly due to the hepatocytes re-entering the cell cycle. That is, the hepatocytes go from the quiescent G0 phase to the G1 phase and undergo mitosis. This process is activated by the p75 receptors.[59] There is also some evidence of bipotential stem cells, called hepatic oval cells or ovalocytes (not to be confused with oval red blood cells of ovalocytosis), which are thought to reside in the canals of Hering. These cells can differentiate into either hepatocytes or cholangiocytes. Cholangiocytes are the epithelial lining cells of the bile ducts.[60] They are cuboidal epithelium in the small interlobular bile ducts, but become columnar and mucus secreting in larger bile ducts approaching the porta hepatis and the extrahepatic ducts. Research is being carried out on the use of stem cells for the generation of an artificial liver.

Scientific and medical works about liver regeneration often refer to the Greek Titan Prometheus who was chained to a rock in the Caucasus where, each day, his liver was devoured by an eagle, only to grow back each night. The myth suggests the ancient Greeks may have known about the liver’s remarkable capacity for self-repair.[61]

Human liver transplants were first performed by Thomas Starzl in the United States and Roy Calne in Cambridge, England in 1963 and 1967, respectively.

Liver transplantation is the only option for those with irreversible liver failure. Most transplants are done for chronic liver diseases leading to cirrhosis, such as chronic hepatitis C, alcoholism, and autoimmune hepatitis. Less commonly, liver transplantation is done for fulminant hepatic failure, in which liver failure occurs over days to weeks.

Liver allografts for transplant usually come from donors who have died from fatal brain injury. Living donor liver transplantation is a technique in which a portion of a living person’s liver is removed (hepatectomy) and used to replace the entire liver of the recipient. This was first performed in 1989 for pediatric liver transplantation. Only 20 percent of an adult’s liver (Couinaud segments 2 and 3) is needed to serve as a liver allograft for an infant or small child.

More recently,[when?] adult-to-adult liver transplantation has been done using the donor’s right hepatic lobe, which amounts to 60 percent of the liver. Due to the ability of the liver to regenerate, both the donor and recipient end up with normal liver function if all goes well. This procedure is more controversial, as it entails performing a much larger operation on the donor, and indeed there have been at least two donor deaths out of the first several hundred cases. A recent publication has addressed the problem of donor mortality, and at least 14 cases have been found.[62] The risk of postoperative complications (and death) is far greater in right-sided operations than that in left-sided operations.

With the recent advances of noninvasive imaging, living liver donors usually have to undergo imaging examinations for liver anatomy to decide if the anatomy is feasible for donation. The evaluation is usually performed by multidetector row computed tomography (MDCT) and magnetic resonance imaging (MRI). MDCT is good in vascular anatomy and volumetry. MRI is used for biliary tree anatomy. Donors with very unusual vascular anatomy, which makes them unsuitable for donation, could be screened out to avoid unnecessary operations.

MDCT image. Arterial anatomy contraindicated for liver donation

MDCT image. Portal venous anatomy contraindicated for liver donation

MDCT image. 3D image created by MDCT can clearly visualize the liver, measure the liver volume, and plan the dissection plane to facilitate the liver transplantation procedure.

Phase contrast CT image. Contrast is perfusing the right liver but not the left due to a left portal vein thrombus.

Some cultures regard the liver as the seat of the soul.[63]

In Greek mythology, the gods punished Prometheus for revealing fire to humans by chaining him to a rock where a vulture (or an eagle) would peck out his liver, which would regenerate overnight. (The liver is the only human internal organ that actually can regenerate itself to a significant extent.) Many ancient peoples of the Near East and Mediterranean areas practiced a type of divination called haruspicy or hepatomancy, where they tried to obtain information by examining the livers of sheep and other animals.

In Plato, and in later physiology, the liver was thought to be the seat of the darkest emotions (specifically wrath, jealousy and greed) which drive men to action.[64] The Talmud (tractate Berakhot 61b) refers to the liver as the seat of anger, with the gallbladder counteracting this.

The Persian, Urdu, and Hindi languages (جگر or जिगर or jigar) refer to the liver figurative speech to indicate courage and strong feelings, or “their best”; e.g., “This Mecca has thrown to you the pieces of its liver!”.[65] The term jan e jigar, literally “the strength (power) of my liver”, is a term of endearment in Urdu. In Persian slang, jigar is used as an adjective for any object which is desirable, especially women. In the Zulu language, the word for liver (isibindi) is the same as the word for courage.

Humans commonly eat the livers of mammals, fowl, and fish as food. Domestic pig, ox, lamb, calf, chicken, and goose livers are widely available from butchers and supermarkets. In the Romance languages, the anatomical word for “liver” (French foie, Spanish hígado, etc.) derives not from the Latin anatomical term, jecur, but from the culinary term ficatum, literally “stuffed with figs,” referring to the livers of geese that had been fattened on figs.[66]

Liver can be baked, boiled, broiled, fried, stir-fried, or eaten raw (asbeh nayeh or sawda naye in Lebanese cuisine, or liver sashimi in Japanese cuisine). In many preparations, pieces of liver are combined with pieces of meat or kidneys, as in the various forms of Middle Eastern mixed grill (e.g. meurav Yerushalmi). Well-known examples include liver pâté, foie gras, chopped liver, and leverpastej. Liver sausages such as Braunschweiger and liverwurst are also a valued meal. Liver sausages may also be used as spreads. A traditional South African delicacy, skilpadjies, is made of minced lamb’s liver wrapped in netvet (caul fat), and grilled over an open fire.

Animal livers are rich in iron, vitamin A and vitamin B12; and cod liver oil is commonly used as a dietary supplement. Traditionally, some fish livers were valued as food, especially the stingray liver. It was used to prepare delicacies, such as poached skate liver on toast in England, as well as the beignets de foie de raie and foie de raie en croute in French cuisine.[67]

The Humr, one of the tribes in the Baggara ethnic grouping, native to southwestern Kordofan in Sudan and speakers of Shuwa or Chadian Arabic, prepare a ( non-alcoholic ) drink from the liver and bone marrow of the giraffe which they call umm nyolokh, and which they claim is intoxicating ( Arabic سكران sakran ), causing dreams and even waking hallucinations.[68] Anthropologist Ian Cunnison, who accompanied the Humr on one of their giraffe-hunting expeditions in the late 1950s, notes that:

It is said that a person, once he has drunk umm nyolokh, will return to giraffe again and again. Humr, being Mahdists, are strict abstainers [ from alcohol ] and a Humrawi is never drunk ( sakran ) on liquor or beer. But he uses this word to describe the effects which umm nyolokh has upon him.[69]

Cunnison’s remarkable account of an apparently psychoactive mammal found its way from a somewhat obscure scientific paper into more mainstream literature through a conversation between Dr. Wendy James of the Institute of Social and Cultural Anthropology at the University of Oxford and specialist on the use of hallucinogens and intoxicants in society Richard Rudgley, who considered its implications in his popular work The Encyclopedia of Psychoactive Substances. Rudgley hypothesises that the presence of the hallucinogenic compound DMT might account for the putative intoxicating properties of umm nyolokh. [68]

Cunnison himself, on the other hand, had found it hard fully to believe in the literal truth of the Humr’s assertion that their drink was intoxicating:

I can only assume that there is no intoxicating substance in the drink and that the effect it produces is simply a matter of convention, although it may be brought about subconsciously.[69]

The study of entheogens in general – including entheogens of animal origin ( e.g. hallucinogenic fish and toad venom ) – has, however made considerable progress in the sixty-odd years since Cunnison’s report and the idea that some intoxicating principle might reside in giraffe liver no longer seems as far-fetched as it was in Cunnison’s day, although conclusive proof ( or disproof ) will have to await detailed analyses of the animal organ in question and the drink prepared therefrom.[68]

Certain Tungusic peoples formerly prepared a type of arrow poison from rotting animal livers, which was, in later times, also applied to bullets. Russian anthropologist Sergei Mikhailovich Shirokogorov, revered as one of the greatest scholars of Tungusic studies, notes that :

Formerly the using of poisoned arrows was common. For instance, among the Kumarčen, [ a subgroup of the Oroqen ] even in recent times a poison was used which was prepared from decaying liver. * ( Note ) This has been confirmed by the Kumarčen. I am not competent to judge as to the chemical conditions of production of poison which is not destroyed by the heat of explosion. However, the Tungus themselves compare this method [ of poisoning ammunition ] with the poisoning of arrows.[70]

The liver is found in all vertebrates, and is typically the largest visceral (internal) organ. Its form varies considerably in different species, and is largely determined by the shape and arrangement of the surrounding organs. Nonetheless, in most species it is divided into right and left lobes; exceptions to this general rule include snakes, where the shape of the body necessitates a simple cigar-like form. The internal structure of the liver is broadly similar in all vertebrates.[71]

An organ sometimes referred to as a liver is found associated with the digestive tract of the primitive chordate Amphioxus. Although it performs many functions of a liver, it is not considered a true liver but a homolog of the vertebrate liver.[72][73][74] The amphioxus hepatic caecum produces the liver-specific proteins vitellogenin, antithrombin, plasminogen, alanine aminotransferase, and insulin/Insulin-like growth factor (IGF)[75]

The pregnancy category of a medication is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does not include any risks conferred by pharmaceutical agents or their metabolites in breast milk.

Every drug has specific information listed in its product literature. The British National Formulary used to provide a table of drugs to be avoided or used with caution in pregnancy, and did so using a limited number of key phrases, but now Appendix 4 (which was the Pregnancy table) has been removed. Appendix 4 is now titled “Intravenous Additives”.[1] However, information that was previously available in the former Appendix 4 (pregnancy) and Appendix 5 (breast feeding) is now available in the individual drug monographs.[2]

American law requires that certain drugs and biological products must be labelled very specifically. Title 21, Part 201.57 (9)(i) of the Code of Federal Regulations lists specific requirements regarding the labeling of drugs with respect to their effects on pregnant populations, including a definition of a “pregnancy category”. These rules are enforced by the Food and Drug Administration.

To supplement this information, FDA publishes additional rules regarding pregnancy and lactation labeling.[3]

The FDA does not regulate labeling for all hazardous and non-hazardous substances. Many substances, including alcohol, are widely known to cause serious hazards to pregnant women and their fetus, including fetal alcohol syndrome. Many other pollutants and hazardous materials are similarly known to cause reproductive harm. However, some of these substances are not subject to drug labeling laws, and are therefore not assigned a “Pregnancy Category” per 21 CFR 201.57.
قرص trimethoprim

One characteristic of the FDA definitions of the pregnancy categories is that the FDA requires a relatively large amount of high-quality data on a pharmaceutical for it to be defined as Pregnancy Category A. As a result of this, many drugs that would be considered Pregnancy Category A in other countries are allocated to Category C by the FDA.

On December 13, 2014, the FDA published the Pregnancy and Lactation Labeling Final Rule (PLLR), which changed the labeling requirements for the pregnancy and lactation sections for prescription drugs and biological agents.[3] The final rule removed the pregnancy letter categories, and created descriptive subsections for pregnancy exposure and risk, lactation, and effects to reproductive potential for females and males. Labeling changes from this rule began on June 30, 2015, with all submissions for prescription drugs and biological agents using the labeling changes immediately. Previously approved drugs from June 30, 2001 will switch to the new labeling gradually. The rule does not affect the labeling of over-the-counter drugs.

Australia has a slightly different pregnancy category system[4] from the United States – notably the subdivision of Category B. (For drugs in B1, B2 and B3 categories, human data are lacking or inadequate. Subcategorisation is based on animal data, and allocation of a B category does not imply greater safety than C category).[5] The system, as outlined below, was developed by medical and scientific experts based on available evidence of risks associated with taking particular medicines while pregnant. Being general in nature it is not presented as medical advice to health professionals or the public.

Some prescribing guides, such as the Australian Medicines Handbook, are shifting away from using pregnancy categories since, inherent in these categories, there is an implied assumption that the alphabetical code is one of safety when this is not always the case. Categorisation does not indicate which stages of fetal development might be affected and does not convey information about the balance between risks and benefits in a particular situation. Additionally, categories are not necessarily maintained or updated with availability of new data.[6]

The data presented is for comparative and illustrative purposes only, and may have been superseded by updated data.

To supplement this information, FDA publishes additional rules regarding pregnancy and lactation labeling.[3]

The data presented is for comparative and illustrative purposes only, and may have been superseded by updated data.

InChI=1S/C14H18N4O3/c1-19-10-5-8(6-11(20-2)12(10)21-3)4-9-7-17-14(16)18-13(9)15/h5-7H,4H2,1-3H3,(H4,15,16,17,18) YKey:IEDVJHCEMCRBQM-UHFFFAOYSA-N Y

تری متوپریم (به انگلیسی: trimethoprim)

رده درمانی: آنتی‌بیوتیک

اشکال دارویی: قرص ، شربت

تری متوپریم یک آنتی بیوتیک باکتریواستاتیک وسیع الطیف است که در درمان عفونتها بخصوص عفونتهای ادراری مصرف دارد. البته اغلب تریمتوپریم به همراه سولفامتوکسازول در ترکیب با هم ( به نام کوتریموکسازول) بکار میرود. در پروفیلاکسی عفونتهای ادراری ، پنوموسیستس کارینی نیز مصرف دارد.
قرص trimethoprim

تریمتوپریم با تداخل در عملکرد آنزیم دی هیدروفولات ردوکتاز باکتریها ساخت اسید تترا هیدروفولیک را مهار میکند. تتراهیدروفولیک اسید کوفاکتور ضروری در ساخت تیمیدین و DNA می باشد. باکتریهایی که اسید فولیک را خودشان تولید می کنند به این دارو حساس هستند لذا این دارو تکثیر آنها را متوقف میکند.

حساسیت به نور ، کم خونی ، سندرم استیونس جانسون ، تهوع و بثورات جلدی.

چنانچه در خصوص “تری متوپریم” سوالی دارید، عارضه خاصی مشاهده نموده اید و یا مطلب ویژه ای به نظرتان می رسد با دیگران به اشتراک بگذارید

%PDF-1.5
%
49 0 obj
>
endobj

77 0 obj
>/Filter/FlateDecode/ID[]/Index[49 46]/Info 48 0 R/Length 124/Prev 93480/Root 50 0 R/Size 95/Type/XRef/W[1 3 1]>>stream
hbbd“`b“ “:*L3A$ 0L^Y`m“g0{)X

Learn about prescription and over-the-counter drugs – how they work, possible side effects, and more.

There are no results for this search

Choose another search set, or input a search term

This information is intended to supplement, not substitute for, the expertise and judgment of your health care professional. The information is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate, or effective for you. You should consult your health care professional before taking any drug, changing your diet, or commencing or discontinuing any course of treatment. First Databank disclaims any liability for the decisions you make based on this information.

قرص trimethoprim

Natural medicines database

Explore reliable information about the safe, effective use of vitamins, herbs, and other supplements and how they interact with other medications.

Search vitamins and herbs

Drug formulary

Find out about drugs approved by the Kaiser Permanente Pharmacy and Therapeutics Committee for use in your care.

Covered drugs

Kaiser Permanente health plans around the country: Kaiser Foundation Health Plan, Inc., in Northern and Southern California and Hawaii • Kaiser Foundation Health Plan of Colorado • Kaiser Foundation Health Plan of Georgia, Inc., Nine Piedmont Center, 3495 Piedmont Road NE, Atlanta, GA 30305, 404-364-7000 • Kaiser Foundation Health Plan of the Mid-Atlantic States, Inc., in Maryland, Virginia, and Washington, D.C., 2101 E. Jefferson St., Rockville, MD 20852 • Kaiser Foundation Health Plan of the Northwest, 500 NE Multnomah St., Suite 100, Portland, OR 97232 • Kaiser Foundation Health Plan of Washington or Kaiser Foundation Health Plan of Washington Options, Inc., 601 Union St., Suite 3100, Seattle, WA 98101

Adobe Acrobat Reader is required to read PDFs.

© 2019 Kaiser Foundation Health Plan, Inc.

sulfamethoxazole

Molecular Weight: 253.2809

trimethoprim

Molecular Weight: 290.321

Several FDA-approved drug labels may be available for sulfamethoxazole/trimethoprim. AIDSinfo provides the following drug label solely as an example of the labels available for sulfamethoxazole/trimethoprim. Inclusion or absence of a drug label on the AIDSinfo site does not imply endorsement or lack thereof by AIDSinfo. Search Drugs@FDA to access more information on sulfamethoxazole/trimethoprim, including additional drug labels and any generic equivalents.قرص trimethoprim

Rx only

BACTRIM (sulfamethoxazole and trimethoprim) is a synthetic antibacterial combination product available in DS (double strength) tablets, each containing 800 mg sulfamethoxazole and 160 mg trimethoprim; in tablets, each containing 400 mg sulfamethoxazole and 80 mg trimethoprim for oral administration.

Sulfamethoxazole is

N1-(5-methyl-3-isoxazolyl)sulfanilamide; the molecular formula is C

10H

11N

3S. It is an almost white, odorless, tasteless compound with a molecular weight of 253.28 and the following structural formula:

Trimethoprim is 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine; the molecular formula is C

14H

18N

3. It is a white to light yellow, odorless, bitter compound with a molecular weight of 290.3 and the following structural formula:

Inactive ingredients: Docusate sodium 85%, sodium benzoate 15%, sodium starch glycolate, magnesium stearate and pregelatinized starch.

BACTRIM is rapidly absorbed following oral administration. Both sulfamethoxazole and trimethoprim exist in the blood as unbound, protein-bound and metabolized forms; sulfamethoxazole also exists as the conjugated form. Sulfamethoxazole is metabolized in humans to at least 5 metabolites: the N

4-acetyl-, N

4-hydroxy-, 5-methylhydroxy-, N

4-acetyl-5-methylhydroxy- sulfamethoxazole metabolites, and an N-glucuronide conjugate. The formulation of N

4-hydroxy metabolite is mediated

via CYP2C9.

Trimethoprim is metabolized

in vitro to 11 different metabolites, of which, five are glutathione adducts and six are oxidative metabolites, including the major metabolites, 1- and 3-oxides and the 3- and 4-hydroxy derivatives.

The free forms of sulfamethoxazole and trimethoprim are considered to be the therapeutically active forms.

In vitro studies suggest that trimethoprim is a substrate of P-glycoprotein, OCT1 and OCT2, and that sulfamethoxazole is not a substrate of P-glycoprotein.

Approximately 70% of sulfamethoxazole and 44% of trimethoprim are bound to plasma proteins. The presence of 10 mg percent sulfamethoxazole in plasma decreases the protein binding of trimethoprim by an insignificant degree; trimethoprim does not influence the protein binding of sulfamethoxazole.

Peak blood levels for the individual components occur 1 to 4 hours after oral administration. The mean serum half-lives of sulfamethoxazole and trimethoprim are 10 and 8 to 10 hours, respectively. However, patients with severely impaired renal function exhibit an increase in the half-lives of both components, requiring dosage regimen adjustment (see

DOSAGE AND ADMINISTRATION section). Detectable amounts of sulfamethoxazole and trimethoprim are present in the blood 24 hours after drug administration. During administration of 800 mg sulfamethoxazole and 160 mg trimethoprim b.i.d., the mean steady-state plasma concentration of trimethoprim was 1.72 µg/mL. The steady-state mean plasma levels of free and total sulfamethoxazole were 57.4 µg/mL and 68.0 µg/mL, respectively. These steady-state levels were achieved after three days of drug administration.

1 Excretion of sulfamethoxazole and trimethoprim is primarily by the kidneys through both glomerular filtration and tubular secretion. Urine concentrations of both sulfamethoxazole and trimethoprim are considerably higher than are the concentrations in the blood. The average percentage of the dose recovered in urine from 0 to 72 hours after a single oral dose of sulfamethoxazole and trimethoprim is 84.5% for total sulfonamide and 66.8% for free trimethoprim. Thirty percent of the total sulfonamide is excreted as free sulfamethoxazole, with the remaining as N

4-acetylated metabolite.

2 When administered together as sulfamethoxazole and trimethoprim, neither sulfamethoxazole nor trimethoprim affects the urinary excretion pattern of the other.

Both sulfamethoxazole and trimethoprim distribute to sputum, vaginal fluid and middle ear fluid; trimethoprim also distributes to bronchial secretion, and both pass the placental barrier and are excreted in human milk.

Geriatric Pharmacokinetics: The pharmacokinetics of sulfamethoxazole 800 mg and trimethoprim 160 mg were studied in 6 geriatric subjects (mean age: 78.6 years) and 6 young healthy subjects (mean age: 29.3 years) using a non-US approved formulation. Pharmacokinetic values for sulfamethoxazole in geriatric subjects were similar to those observed in young adult subjects. The mean renal clearance of trimethoprim was significantly lower in geriatric subjects compared with young adult subjects (19 mL/h/kg vs. 55 mL/h/kg). However, after normalizing by body weight, the apparent total body clearance of trimethoprim was on average 19% lower in geriatric subjects compared with young adult subjects.

Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA). Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting the required enzyme, dihydrofolate reductase. Thus, sulfamethoxazole and trimethoprim blocks two consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria.

In vitro studies have shown that bacterial resistance develops more slowly with both sulfamethoxazole and trimethoprim in combination than with either sulfamethoxazole or trimethoprim alone.

Sulfamethoxazole and trimethoprim have been shown to be active against most strains of the following microorganisms, both

in vitro and in clinical infections as described in the

INDICATIONS AND USAGE section.

Aerobic gram-positive microorganisms:Streptococcus pneumoniae

Aerobic gram-negative microorganisms:Escherichia coli (including susceptible enterotoxigenic strains implicated in traveler’s diarrhea)

Klebsiella species

Enterobacter species

Haemophilus influenzae Morganella morganii Proteus mirabilis Proteus vulgaris Shigella flexneri Shigella sonnei

Other Organisms:Pneumocystis jiroveci

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Bactrim (sulfamethoxazole and trimethoprim) tablets and other antibacterial drugs, Bactrim (sulfamethoxazole and trimethoprim) tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to empiric selection of therapy.

Urinary Tract Infections: For the treatment of urinary tract infections due to susceptible strains of the following organisms:

Escherichia coli,

Klebsiella species,

Enterobacter species,

Morganella morganii,

Proteus mirabilis and

Proteus vulgaris. It is recommended that initial episodes of uncomplicated urinary tract infections be treated with a single effective antibacterial agent rather than the combination.

Acute Otitis Media: For the treatment of acute otitis media in pediatric patients due to susceptible strains of

Streptococcus pneumoniae or

Haemophilus influenzae when in the judgment of the physician sulfamethoxazole and trimethoprim offers some advantage over the use of other antimicrobial agents. To date, there are limited data on the safety of repeated use of BACTRIM in pediatric patients under two years of age. BACTRIM is not indicated for prophylactic or prolonged administration in otitis media at any age.

قرص trimethoprim

Acute Exacerbations of Chronic Bronchitis in Adults: For the treatment of acute exacerbations of chronic bronchitis due to susceptible strains of

Streptococcus pneumoniae or

Haemophilus influenzae when a physician deems that BACTRIM could offer some advantage over the use of a single antimicrobial agent.

Shigellosis: For the treatment of enteritis caused by susceptible strains of

Shigella flexneri and

Shigella sonnei when antibacterial therapy is indicated.

Pneumocystis jiroveci Pneumonia: For the treatment of documented

Pneumocystis jiroveci pneumonia and for prophylaxis against

P. jiroveci pneumonia in individuals who are immunosuppressed and considered to be at an increased risk of developing

P. jiroveci pneumonia.

Traveler’s Diarrhea in Adults: For the treatment of traveler’s diarrhea due to susceptible strains of enterotoxigenic

E. coli.

BACTRIM is contraindicated in patients with a known hypersensitivity to trimethoprim or sulfonamides, in patients with a history of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides, and in patients with documented megaloblastic anemia due to folate deficiency.

BACTRIM is contraindicated in pediatric patients less than 2 months of age. BACTRIM is also contraindicated in patients with marked hepatic damage or with severe renal insufficiency when renal function status cannot be monitored.

Embryofetal Toxicity

Some epidemiologic studies suggest that exposure to sulfamethoxazole/trimethoprim during pregnancy may be associated with an increased risk of congenital malformations, particularly neural tube defects, cardiovascular malformations, urinary tract defects, oral clefts, and club foot. If sulfamethoxazole/trimethoprim is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be advised of the potential hazards to the fetus.

Hypersensitivity and Other Fatal Reactions

Fatalities associated with the administration of sulfonamides, although rare, have occurred due to severe reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias.

Sulfonamides, including sulfonamide-containing products such as sulfamethoxazole/trimethoprim, should be discontinued at the first appearance of skin rash or any sign of adverse reaction. In rare instances, a skin rash may be followed by a more severe reaction, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, and serious blood disorders (see

PRECAUTIONS). Clinical signs, such as rash, sore throat, fever, arthralgia, pallor, purpura or jaundice may be early indications of serious reactions.

Cough, shortness of breath, and pulmonary infiltrates are hypersensitivity reactions of the respiratory tract that have been reported in association with sulfonamide treatment.

Thrombocytopenia

Sulfamethoxazole/trimethoprim-induced thrombocytopenia may be an immune-mediated disorder. Severe cases of thrombocytopenia that are fatal or life threatening have been reported. Thrombocytopenia usually resolves within a week upon discontinuation of sulfamethoxazole/trimethoprim.

Streptococcal Infections and Rheumatic Fever

The sulfonamides should not be used for treatment of group A β-hemolytic streptococcal infections. In an established infection, they will not eradicate the streptococcus and, therefore, will not prevent sequelae such as rheumatic fever.

Clostridium difficile associated diarrhea

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including BACTRIM, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of

C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of

C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against

C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of

C. difficile, and surgical evaluation should be instituted as clinically indicated.

Adjunctive treatment with Leucovorin for Pneumocystis jiroveci pneumonia

Treatment failure and excess mortality were observed when trimethoprim-sulfamethoxazole was used concomitantly with leucovorin for the treatment of HIV positive patients with

Pneumocystis jiroveci pneumonia in a randomized placebo controlled trial.

6 Co-administration of trimethoprim-sulfamethoxazole and leucovorin during treatment of

Pneumocystis jiroveci pneumonia should be avoided.

Development of drug resistant bacteria

Prescribing Bactrim (sulfamethoxazole and trimethoprim) tablets in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Folate deficiency

BACTRIM should be given with caution to patients with impaired renal or hepatic function, to those with possible folate deficiency (e.g., the elderly, chronic alcoholics, patients receiving anticonvulsant therapy, patients with malabsorption syndrome, and patients in malnutrition states) and to those with severe allergies or bronchial asthma.

Hematological changes indicative of folic acid deficiency may occur in elderly patients or in patients with preexisting folic acid deficiency or kidney failure. These effects are reversible by folinic acid therapy.

Hemolysis

In glucose-6-phosphate dehydrogenase deficient individuals, hemolysis may occur. This reaction is frequently dose-related (see

CLINICAL PHARMACOLOGY and

DOSAGE AND ADMINISTRATION).

Hypoglycemia

Cases of hypoglycemia in non-diabetic patients treated with BACTRIM are seen rarely, usually occurring after a few days of therapy. Patients with renal dysfunction, liver disease, malnutrition or those receiving high doses of BACTRIM are particularly at risk.

Phenylalanine metabolism

Trimethoprim has been noted to impair phenylalanine metabolism, but this is of no significance in phenylketonuric patients on appropriate dietary restriction.

Porphyria and Hypothyroidism

As with all drugs containing sulfonamides, caution is advisable in patients with porphyria or thyroid dysfunction.

Use in the Treatment of and Prophylaxis for Pneumocystis jiroveci Pneumonia in Patients with Acquired Immunodeficiency Syndrome (AIDS): AIDS patients may not tolerate or respond to BACTRIM in the same manner as non-AIDS patients. The incidence of side effects, particularly rash, fever, leukopenia and elevated aminotransferase (transaminase) values, with BACTRIM therapy in AIDS patients who are being treated for

P. jiroveci pneumonia has been reported to be greatly increased compared with the incidence normally associated with the use of BACTRIM in non-AIDS patients. Adverse effects are generally less severe in patients receiving BACTRIM for prophylaxis. A history of mild intolerance to BACTRIM in AIDS patients does not appear to predict intolerance of subsequent secondary prophylaxis.

7 However, if a patient develops skin rash or any sign of adverse reaction, therapy with BACTRIM should be reevaluated (see

WARNINGS).

Co-administration of BACTRIM and leucovorin should be avoided with

P. jiroveci pneumonia (see

WARNINGS).

Electrolyte Abnormalities

High dosage of trimethoprim, as used in patients with

P. jiroveci pneumonia, induces a progressive but reversible increase of serum potassium concentrations in a substantial number of patients. Even treatment with recommended doses may cause hyperkalemia when trimethoprim is administered to patients with underlying disorders of potassium metabolism, with renal insufficiency, or if drugs known to induce hyperkalemia are given concomitantly. Close monitoring of serum potassium is warranted in these patients.

Severe and symptomatic hyponatremia can occur in patients receiving BACTRIM, particularly for the treatment of

P. jiroveci pneumonia. Evaluation for hyponatremia and appropriate correction is necessary in symptomatic patients to prevent life-threatening complications.

During treatment, adequate fluid intake and urinary output should be ensured to prevent crystalluria. Patients who are “slow acetylators” may be more prone to idiosyncratic reactions to sulfonamides.

Information for Patients: Patients should be counseled that antibacterial drugs including Bactrim (sulfamethoxazole and trimethoprim) tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Bactrim (sulfamethoxazole and trimethoprim) tablets are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Bactrim (sulfamethoxazole and trimethoprim) tablets or other antibacterial drugs in the future.

Patients should be instructed to maintain an adequate fluid intake in order to prevent crystalluria and stone formation.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Laboratory Tests: Complete blood counts should be done frequently in patients receiving BACTRIM; if a significant reduction in the count of any formed blood element is noted, BACTRIM should be discontinued. Urinalyses with careful microscopic examination and renal function tests should be performed during therapy, particularly for those patients with impaired renal function.

Drug Interactions:

Potential for BACTRIM to Affect Other Drugs

Trimethoprim is an inhibitor of CYP2C8 as well as OCT2 transporter. Sulfamethoxazole is an inhibitor of CYP2C9. Caution is recommended when Bactrim is co-administered with drugs that are substrates of CYP2C8 and 2C9 or OCT2.

In elderly patients concurrently receiving certain diuretics, primarily thiazides, an increased incidence of thrombocytopenia with purpura has been reported.

It has been reported that BACTRIM may prolong the prothrombin time in patients who are receiving the anticoagulant warfarin (a CYP2C9 substrate). This interaction should be kept in mind when BACTRIM is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed.

BACTRIM may inhibit the hepatic metabolism of phenytoin (a CYP2C9 substrate). BACTRIM, given at a common clinical dosage, increased the phenytoin half-life by 39% and decreased the phenytoin metabolic clearance rate by 27%. When administering these drugs concurrently, one should be alert for possible excessive phenytoin effect.

Sulfonamides can also displace methotrexate from plasma protein binding sites and can compete with the renal transport of methotrexate, thus increasing free methotrexate concentrations.

There have been reports of marked but reversible nephrotoxicity with coadministration of BACTRIM and cyclosporine in renal transplant recipients.

Increased digoxin blood levels can occur with concomitant BACTRIM therapy, especially in elderly patients. Serum digoxin levels should be monitored.

Increased sulfamethoxazole blood levels may occur in patients who are also receiving indomethacin.

Occasional reports suggest that patients receiving pyrimethamine as malaria prophylaxis in doses exceeding 25 mg weekly may develop megaloblastic anemia if BACTRIM is prescribed.

The efficacy of tricyclic antidepressants can decrease when coadministered with BACTRIM.

BACTRIM potentiates the effect of oral hypoglycemics that are metabolized by CYP2C8 (e.g., pioglitazone, repaglinide, and rosiglitazone) or CYP2C9 (e.g., glipizide and glyburide) or eliminated renally

via OCT2 (e.g., metformin). Additional monitoring of blood glucose may be warranted.

In the literature, a single case of toxic delirium has been reported after concomitant intake of sulfamethoxazole/trimethoprim and amantadine (an OCT2 substrate). Cases of interactions with other OCT2 substrates, memantine and metformin, have also been reported.

In the literature, three cases of hyperkalemia in elderly patients have been reported after concomitant intake of sulfamethoxazole/trimethoprim and an angiotensin converting enzyme inhibitor.

8,9

Drug/Laboratory Test Interactions: BACTRIM, specifically the trimethoprim component, can interfere with a serum methotrexate assay as determined by the competitive binding protein technique (CBPA) when a bacterial dihydrofolate reductase is used as the binding protein. No interference occurs, however, if methotrexate is measured by a radioimmunoassay (RIA).

The presence of sulfamethoxazole and trimethoprim may also interfere with the Jaffé alkaline picrate reaction assay for creatinine, resulting in overestimations of about 10% in the range of normal values.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Carcinogenesis: Sulfamethoxazole was not carcinogenic when assessed in a 26-week tumorigenic mouse (Tg-rasH2) study at doses up to 400 mg/kg/day sulfamethoxazole; equivalent to 2.4-fold the human systemic exposure (at a daily dose of 800 mg sulfamethoxazole

b.i.d.).

Mutagenesis: In vitro reverse mutation bacterial tests according to the standard protocol have not been performed with sulfamethoxazole and trimethoprim in combination. An

in vitro chromosomal aberration test in human lymphocytes with sulfamethoxazole/trimethoprim was negative. In

in vitro and

in vivo tests in animal species, sulfamethoxazole/trimethoprim did not damage chromosomes.

In vivo micronucleus assays were positive following oral administration of sulfamethoxazole/trimethoprim. Observations of leukocytes obtained from patients treated with sulfamethoxazole and trimethoprim revealed no chromosomal abnormalities.

Sulfamethoxazole alone was positive in an

in vitro reverse mutation bacterial assay and in

in vitro micronucleus assays using cultured human lymphocytes.

Trimethoprim alone was negative in

in vitro reverse mutation bacterial assays and in

in vitro chromosomal aberration assays with Chinese Hamster ovary or lung cells with or without S9 activation. In

in vitro Comet, micronucleus and chromosomal damage assays using cultured human lymphocytes, trimethoprim was positive. In mice following oral administration of trimethoprim, no DNA damage in Comet assays of liver, kidney, lung, spleen, or bone marrow was recorded.

Impairment of Fertility: No adverse effects on fertility or general reproductive performance were observed in rats given oral dosages as high as 350 mg/kg/day sulfamethoxazole plus 70 mg/kg/day trimethoprim, doses roughly two times the recommended human daily dose on a body surface area basis.

Pregnancy:

While there are no large, well-controlled studies on the use of sulfamethoxazole and trimethoprim in pregnant women, Brumfitt and Pursell,

10 in a retrospective study, reported the outcome of 186 pregnancies during which the mother received either placebo or sulfamethoxazole and trimethoprim. The incidence of congenital abnormalities was 4.5% (3 of 66) in those who received placebo and 3.3% (4 of 120) in those receiving sulfamethoxazole and trimethoprim. There were no abnormalities in the 10 children whose mothers received the drug during the first trimester. In a separate survey, Brumfitt and Pursell also found no congenital abnormalities in 35 children whose mothers had received oral sulfamethoxazole and trimethoprim at the time of conception or shortly thereafter.

Because sulfamethoxazole and trimethoprim may interfere with folic acid metabolism, BACTRIM should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Teratogenic Effects:

Human Data:

While there are no large prospective, well controlled studies in pregnant women and their babies, some retrospective epidemiologic studies suggest an association between first trimester exposure to sulfamethoxazole/trimethoprim with an increased risk of congenital malformations, particularly neural tube defects, cardiovascular abnormalities, urinary tract defects, oral clefts, and club foot. These studies, however, were limited by the small number of exposed cases and the lack of adjustment for multiple statistical comparisons and confounders. These studies are further limited by recall, selection, and information biases, and by limited generalizability of their findings. Lastly, outcome measures varied between studies, limiting cross-study comparisons. Alternatively, other epidemiologic studies did not detect statistically significant associations between sulfamethoxazole/trimethoprim exposure and specific malformations.

Animal Data:

In rats, oral doses of either 533 mg/kg sulfamethoxazole or 200 mg/kg trimethoprim produced teratologic effects manifested mainly as cleft palates. These doses are approximately 5 and 6 times the recommended human total daily dose on a body surface area basis. In two studies in rats, no teratology was observed when 512 mg/kg of sulfamethoxazole was used in combination with 128 mg/kg of trimethoprim. In some rabbit studies, an overall increase in fetal loss (dead and resorbed conceptuses) was associated with doses of trimethoprim 6 times the human therapeutic dose based on body surface area.

Nonteratogenic Effects: See

CONTRAINDICATIONS section.

Nursing Mothers: Levels of trimethoprim/sulfamethoxazole in breast milk are approximately 2–5% of the recommended daily dose for infants over 2 months of age. Caution should be exercised when BACTRIM is administered to a nursing woman, especially when breastfeeding, jaundiced, ill, stressed, or premature infants because of the potential risk of bilirubin displacement and kernicterus.

Pediatric Use: BACTRIM is contraindicated for infants younger than 2 months of age (see

INDICATIONS and

CONTRAINDICATIONS sections).

Geriatric Use: Clinical studies of BACTRIM did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

There may be an increased risk of severe adverse reactions in elderly patients, particularly when complicating conditions exist, e.g., impaired kidney and/or liver function, possible folate deficiency, or concomitant use of other drugs. Severe skin reactions, generalized bone marrow suppression (see

WARNINGS and

ADVERSE REACTIONS sections), a specific decrease in platelets (with or without purpura), and hyperkalemia are the most frequently reported severe adverse reactions in elderly patients. In those concurrently receiving certain diuretics, primarily thiazides, an increased incidence of thrombocytopenia with purpura has been reported. Increased digoxin blood levels can occur with concomitant BACTRIM therapy, especially in elderly patients. Serum digoxin levels should be monitored. Hematological changes indicative of folic acid deficiency may occur in elderly patients. These effects are reversible by folinic acid therapy. Appropriate dosage adjustments should be made for patients with impaired kidney function and duration of use should be as short as possible to minimize risks of undesired reactions (see

DOSAGE AND ADMINISTRATION section). The trimethoprim component of BACTRIM may cause hyperkalemia when administered to patients with underlying disorders of potassium metabolism, with renal insufficiency or when given concomitantly with drugs known to induce hyperkalemia, such as angiotensin converting enzyme inhibitors. Close monitoring of serum potassium is warranted in these patients. Discontinuation of BACTRIM treatment is recommended to help lower potassium serum levels. Bactrim Tablets contain 1.8 mg sodium (0.08 mEq) of sodium per tablet. Bactrim DS Tablets contain 3.6 mg (0.16 mEq) of sodium per tablet.

Pharmacokinetics parameters for sulfamethoxazole were similar for geriatric subjects and younger adult subjects. The mean maximum serum trimethoprim concentration was higher and mean renal clearance of trimethoprim was lower in geriatric subjects compared with younger subjects (see

CLINICAL PHARMACOLOGY: Geriatric Pharmacokinetics).

The most common adverse effects are gastrointestinal disturbances (nausea, vomiting, anorexia) and allergic skin reactions (such as rash and urticaria).

FATALITIES ASSOCIATED WITH THE ADMINISTRATION OF SULFONAMIDES, ALTHOUGH RARE, HAVE OCCURRED DUE TO SEVERE REACTIONS, INCLUDING STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, FULMINANT HEPATIC NECROSIS, AGRANULOCYTOSIS, APLASTIC ANEMIA AND OTHER BLOOD DYSCRASIAS (SEE

WARNINGS SECTION).

Hematologic: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia.

Allergic Reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills, Henoch-Schoenlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral injection, pruritus, urticaria and rash. In addition, periarteritis nodosa and systemic lupus erythematosus have been reported.

Gastrointestinal: Hepatitis (including cholestatic jaundice and hepatic necrosis), elevation of serum transaminase and bilirubin, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal pain, diarrhea, anorexia.

Genitourinary: Renal failure, interstitial nephritis, BUN and serum creatinine elevation, toxic nephrosis with oliguria and anuria, crystalluria and nephrotoxicity in association with cyclosporine.

Metabolic and Nutritional: Hyperkalemia, hyponatremia (see

PRECAUTIONS: Electrolyte Abnormalities).

Neurologic: Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, headache.

Psychiatric: Hallucinations, depression, apathy, nervousness.

Endocrine: The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycemic agents. Cross-sensitivity may exist with these agents. Diuresis and hypoglycemia have occurred rarely in patients receiving sulfonamides.

Musculoskeletal: Arthralgia and myalgia. Isolated cases of rhabdomyolysis have been reported with BACTRIM, mainly in AIDS patients.

Respiratory: Cough, shortness of breath and pulmonary infiltrates (see

WARNINGS).

Miscellaneous: Weakness, fatigue, insomnia.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of trimethoprim-sulfamethoxazole. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

Acute: The amount of a single dose of BACTRIM that is either associated with symptoms of overdosage or is likely to be life-threatening has not been reported. Signs and symptoms of overdosage reported with sulfonamides include anorexia, colic, nausea, vomiting, dizziness, headache, drowsiness and unconsciousness. Pyrexia, hematuria and crystalluria may be noted. Blood dyscrasias and jaundice are potential late manifestations of overdosage.

Signs of acute overdosage with trimethoprim include nausea, vomiting, dizziness, headache, mental depression, confusion and bone marrow depression.

General principles of treatment include the institution of gastric lavage or emesis, forcing oral fluids, and the administration of intravenous fluids if urine output is low and renal function is normal. Acidification of the urine will increase renal elimination of trimethoprim. The patient should be monitored with blood counts and appropriate blood chemistries, including electrolytes. If a significant blood dyscrasia or jaundice occurs, specific therapy should be instituted for these complications. Peritoneal dialysis is not effective and hemodialysis is only moderately effective in eliminating sulfamethoxazole and trimethoprim.

Chronic: Use of BACTRIM at high doses and/or for extended periods of time may cause bone marrow depression manifested as thrombocytopenia, leukopenia and/or megaloblastic anemia. If signs of bone marrow depression occur, the patient should be given leucovorin 5 to 15 mg daily until normal hematopoiesis is restored.

BACTRIM is contraindicated in pediatric patients less than 2 months of age.

Urinary Tract Infections and Shigellosis in Adults and Pediatric Patients, and Acute Otitis Media in Children:

Adults: The usual adult dosage in the treatment of urinary tract infections is 1 BACTRIM DS (double strength) tablet or 2 BACTRIM tablets every 12 hours for 10 to 14 days. An identical daily dosage is used for 5 days in the treatment of shigellosis.

Children: The recommended dose for children with urinary tract infections or acute otitis media is 40 mg/kg sulfamethoxazole and 8 mg/kg trimethoprim per 24 hours, given in two divided doses every 12 hours for 10 days. An identical daily dosage is used for 5 days in the treatment of shigellosis. The following table is a guideline for the attainment of this dosage:

22

10 –

44

20

1

66

30 1½

88

40 2 or 1 DS tablet

For Patients with Impaired Renal Function: When renal function is impaired, a reduced dosage should be employed using the following table:

Above 30

Usual standard regimen

15–30

½ the usual regimen

Below 15

Use not recommended

Acute Exacerbations of Chronic Bronchitis in Adults:

The usual adult dosage in the treatment of acute exacerbations of chronic bronchitis is 1 BACTRIM DS (double strength) tablet or 2 BACTRIM tablets every 12 hours for 14 days.

Pneumocystis Jiroveci Pneumonia:

Treatment: Adults and Children:

The recommended dosage for treatment of patients with documented

Pneumocystis jiroveci pneumonia is 75 to 100 mg/kg sulfamethoxazole and 15 to 20 mg/kg trimethoprim per 24 hours given in equally divided doses every 6 hours for 14 to 21 days.

11 The following table is a guideline for the upper limit of this dosage:

18

8 –

35

16

1

53

24 1½

70

32 2 or 1 DS tablet

88

40 2½

106

48 3 or 1½ DS tablets

141

64 4 or 2 DS tablets

176

80 5 or 2½ DS tablets

For the lower limit dose (75 mg/kg sulfamethoxazole and 15 mg/kg trimethoprim per 24 hours) administer 75% of the dose in the above table.

Prophylaxis:

Adults:

The recommended dosage for prophylaxis in adults is 1 BACTRIM DS (double strength) tablet daily.

Children:

For children, the recommended dose is 750 mg/m

2/day sulfamethoxazole with 150 mg/m

2/day trimethoprim given orally in equally divided doses twice a day, on 3 consecutive days per week. The total daily dose should not exceed 1600 mg sulfamethoxazole and 320 mg trimethoprim.

13 The following table is a guideline for the attainment of this dosage in children:

0.26 –

0.53 ½

1.06

1 Traveler’s Diarrhea in Adults:

For the treatment of traveler’s diarrhea, the usual adult dosage is 1 BACTRIM DS (double strength) tablet or 2 BACTRIM tablets every 12 hours for 5 days.

BACTRIM™ TABLETS are supplied as follows:

BACTRIM™ DS (double strength) TABLETS (white, oval shaped, scored) containing 160 mg trimethoprim and 800 mg sulfamethoxazole – bottles of 100 (NDC 49708-146-01). Imprint on tablets (debossed): (front) BACTRIM DS

BACTRIM™ TABLETS (white, round, scored) containing 80 mg trimethoprim and 400 mg sulfamethoxazole – bottles of 100 (NDC 49708-145-01). Imprint on tablets (debossed): (front) BACTRIM

Store at 20° to 25°C (68° to 77°F).

[See USP Controlled Room Temperature]

DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.

Kremers P, Duvivier J, Heusghem C. Pharmacokinetic Studies of Co-Trimoxazole in Man after Single and Repeated Doses. J Clin Pharmacol. Feb-Mar 1974; 14:112–117.

Kaplan SA, et al. Pharmacokinetic Profile of Trimethoprim-Sulfamethoxazole in Man. J Infect Dis. Nov 1973; 128 (Suppl): S547–S555.

Varoquaux O, et al. Pharmacokinetics of the trimethoprim-sulfamethoxazole combination in the elderly. Br J Clin Pharmacol. 1985;20:575–581.

Safrin S, Lee BL, Sande MA.Adjunctive folinic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death.J Infect Dis. 1994 Oct;170(4):912–7.

Hardy DW, et al. A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1992; 327: 1842–1848.

Marinella Mark A. 1999. Trimethoprim-induced hyperkalemia: An analysis of reported cases. Gerontol. 45:209–212.

Margassery, S. and B. Bastani. 2002. Life threatening hyperkalemia and acidosis secondary to trimethoprim-sulfamethoxazole treatment. J. Nephrol. 14:410–414.

Brumfitt W, Pursell R. Trimethoprim/Sulfamethoxazole in the Treatment of Bacteriuria in Women. J Infect Dis. Nov 1973; 128 (Suppl):S657–S663.

Masur H. Prevention and treatment of Pneumocystis pneumonia. N Engl J Med. 1992; 327: 1853–1880.

Recommendations for prophylaxis against Pneumocystis carinii pneumonia for adults and adolescents infected with human immunodeficiency virus. MMWR. 1992; 41(RR–4):1–11.

CDC Guidelines for prophylaxis against Pneumocystis carinii pneumonia for children infected with human immunodeficiency virus. MMWR. 1991; 40(RR–2):1–13.

BACTRIM™ and BACTRIM™ DS are trademarks of Hoffmann-La Roche Inc.

Distributed by:Sun Pharmaceutical Industries, Inc.Cranbury, NJ 08512

Rev 03, April 2018

Revised: 08/2018 Sun Pharmaceutical Industries, Inc

PDF documents can be viewed with the free Adobe Reader

Site Updated: July 13, 2019

Loading…

Working…

Loading…

قرص trimethoprim

Working…

Loading…

Working…

Loading…

http://www.rxwiki.com/sulfamethoxazol…https://www.youtube.com/playlist?list…Sulfamethoxazole and trimethoprim is a prescription medication used to treat bacterial infections of the urinary tract, lungs, intestines, ears, and infections that cause traveler’s diarrhea. It is a single tablet containing 2 drugs, sulfamethoxazole and trimethoprim. Sulfamethoxazole and trimethoprim both belong to a group of drugs called antibiotics, which work by stopping bacterial growth.Sulfamethoxazole and trimethoprim come in tablet and oral suspension forms and is taken up to 4 times a day, with or without food.Common side effects of sulfamethoxazole and trimethoprim include diarrhea, vomiting, anorexia, and skin reactions like hives or itching.