Trimethoprim/sulfamethoxazole, sold under the brand name Bactrim among others, is a fixed-dose combination

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...

medication used to treat a variety of

bacterial infection Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and are often beneficial but others can cause infectious diseases. The number ...

s. It consists of one part trimethoprim to five parts sulfamethoxazole. It is used to treat

urinary tract infections A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidne ...

methicillin-resistant Staphylococcus aureus Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of Gram-positive bacteria that are genetically distinct from other strains of '' Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in human ...

(MRSA) skin infections,

travelers' diarrhea Travelers' diarrhea (TD) is a stomach and intestinal infection. TD is defined as the passage of unformed stool (one or more by some definitions, three or more by others) while traveling. It may be accompanied by abdominal cramps, nausea, fever, ...

, respiratory tract infections, and

cholera Cholera is an infection of the small intestine by some strains of the bacterium '' Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting an ...

, among others. It is used both to treat and prevent

pneumocystis pneumonia ''Pneumocystis'' pneumonia (PCP), also known as ''Pneumocystis jirovecii'' pneumonia (PJP), is a form of pneumonia that is caused by the yeast-like fungus ''Pneumocystis jirovecii''. ''Pneumocystis'' specimens are commonly found in the lungs of ...

and

toxoplasmosis Toxoplasmosis is a parasitic disease caused by '' Toxoplasma gondii'', an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. Occasionally, people may have a few weeks or mont ...

in people with

HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...

and other causes of immunosuppression. It can be given

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

or intravenously. Trimethoprim/sulfamethoxazole is on the World Health Organization's List of Essential Medicines and is also available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ...

. In 2020, it was the 121st most commonly prescribed medication in the United States, with more than 5million prescriptions.

Medical uses

''Pneumocystis jirovecii'' pneumonia

Trimethoprim/sulfamethoxazole (TMP/SMX) is the medicine most commonly used to prevent ''Pneumocystis jirovecii'' pneumonia (PCP) People who get ''Pneumocystis'' pneumonia have a medical condition that weakens their

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

, like

, or take medicines (such as

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are inv ...

s) that reduce the body's ability to fight

bacterial Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were amon ...

and

viral infections A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells. Structural Characteristics Basic structural characteristics, ...

. People with HIV/AIDS are less likely to get ''Pneumocystis'' pneumonia as a result of

antiretroviral therapy The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multi ...

(ART). However, ''Pneumocystis'' pneumonia is still a substantial public health problem. Most of what is scientifically known about ''Pneumocystis'' pneumonia and its treatment comes from studying people with HIV/AIDS.

Susceptibility

Organisms against which trimethoprim/sulfamethoxazole can be effective include: * '' Acinetobacter'' spp. * ''

Aeromonas ''Aeromonas'' is a genus of Gram-negative, facultative anaerobic, rod-shaped bacteria that morphologically resemble members of the family Enterobacteriaceae. Most of the 14 described species have been associated with human diseases. The most imp ...

'' spp. * ''

Alcaligenes ''Alcaligenes'' is a genus of Gram-negative, aerobic, rod-shaped bacteria. The species are motile with amphitrichous flagella and rarely nonmotile. It is a genus of non-fermenting bacteria (in the family Alcaligenaceae). Additionally, some str ...

''/''

Achromobacter ''Achromobacter'' is a genus of bacteria, included in the family Alcaligenaceae in the order Burkholderiales. The cells are Gram-negative straight rods and are motile by using one to 20 peritrichous flagella. They are strictly aerobic and are ...

'' spp. * '' Bartonella henselae'' * ''

Bordetella pertussis ''Bordetella pertussis'' is a Gram-negative, aerobic, pathogenic, encapsulated coccobacillus of the genus ''Bordetella'', and the causative agent of pertussis or whooping cough. Like '' B. bronchiseptica'', ''B. pertussis'' is motile and exp ...

'' ( pertussis) * '' Brucella'' spp. * ''

Burkholderia cepacia ''Burkholderia cepacia'' complex (BCC), or simply ''Burkholderia cepacia'', is a group of catalase-producing, lactose-nonfermenting, Gram-negative bacteria composed of at least 20 different species, including ''B. cepacia'', '' B. m ...

'' * ''

Burkholderia mallei ''Burkholderia mallei'' is a Gram-negative, bipolar, aerobic bacterium, a human and animal pathogen of genus ''Burkholderia'' causing glanders; the Latin name of this disease (''malleus'') gave its name to the species causing it. It is closel ...

'' ( glanders) * '' Burkholderia pseudomallei'' (

melioidosis Melioidosis is an infectious disease caused by a gram-negative bacterium called ''Burkholderia pseudomallei''. Most people exposed to ''B. pseudomallei'' experience no symptoms; however, those who do experience symptoms have signs and symptoms ...

) * ''

Chlamydia Chlamydia, or more specifically a chlamydia infection, is a sexually transmitted infection caused by the bacterium '' Chlamydia trachomatis''. Most people who are infected have no symptoms. When symptoms do appear they may occur only several we ...

'' spp. * ''

Chryseobacterium meningosepticum ''Elizabethkingia meningoseptica'' is a Gram-negative, rod-shaped bacterium widely distributed in nature (e.g. fresh water, salt water, or soil). It may be normally present in fish and frogs; it may be isolated from chronic infectious states, ...

'' * ''

Citrobacter ''Citrobacter'' is a genus of Gram-negative coliform bacteria in the family Enterobacteriaceae. The species ''C. amalonaticus'', ''C. koseri'', and ''C. freundii'' can use citrate as a sole carbon source. ''Citrobacter'' species are different ...

'' spp. * ''

Enterobacter ''Enterobacter'' is a genus of common Gram-negative, facultatively anaerobic, rod-shaped, non-spore-forming bacteria of the family Enterobacteriaceae. It is the type genus of the order Enterobacterales. Several strains of these bacteria are ...

'' spp. * ''

Enterococcus ''Enterococcus'' is a large genus of lactic acid bacteria of the phylum Bacillota. Enterococci are gram-positive cocci that often occur in pairs (diplococci) or short chains, and are difficult to distinguish from streptococci on physical char ...

'' spp. * ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...

'' * ''

Haemophilus ''Haemophilus'' is a genus of Gram-negative, pleomorphic, coccobacilli bacteria belonging to the family Pasteurellaceae. While ''Haemophilus'' bacteria are typically small coccobacilli, they are categorized as pleomorphic bacteria because of ...

spp.'' * ''

Hafnia alvei ''Hafnia'' is a genus of Gram-negative, facultatively anaerobic, rod-shaped bacteria in the family Hafniaceae. ''H. alvei'' is a commensal of the human gastrointestinal tract and not normally pathogenic, but may cause disease in immunocompr ...

'' * ''

Kingella ''Kingella'' is a genus of bacteria of the family Neisseriaceae. It belongs to the HACEK group of fastidious Gram-negative bacteria that tend to cause endocarditis. ''Kingella kingae'' is its type species. Species As of 2021, five species bel ...

'' spp. * '' Klebsiella granulomatis'' * '' Klebsiella pneumoniae'' * '' Legionella'' spp. * '' Listeria monocytogenes'' ( listeriosis) * '' Moraxella catarrhalis'' * ''

Morganella morganii ''Morganella morganii'' is a species of Gram-negative bacteria.eMedicineMorganella infections/ref> It has a commensal relationship within the intestinal tracts of humans, mammals, and reptiles as normal flora. Although ''M. morganii'' has a wide ...

'' * ''

Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on it ...

'' (

tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, ...

) * ''

Neisseria gonorrhoeae ''Neisseria gonorrhoeae'', also known as ''gonococcus'' (singular), or ''gonococci'' (plural), is a species of Gram-negative diplococci bacteria isolated by Albert Neisser in 1879. It causes the sexually transmitted genitourinary infection gon ...

'' ( gonorrhoea) * '' Neisseria meningitidis'' (

meningococcal disease Meningococcal disease describes infections caused by the bacterium ''Neisseria meningitidis'' (also termed meningococcus). It has a high mortality rate if untreated but is vaccine-preventable. While best known as a cause of meningitis, it can al ...

) * ''

Nocardia ''Nocardia'' is a genus of weakly staining Gram-positive, catalase-positive, rod-shaped bacteria. It forms partially acid-fast beaded branching filaments (acting as fungi, but being truly bacteria). It contains a total of 85 species. Some sp ...

'' spp. * '' Plesiomonas shigelloides'' * ''

Pneumocystis jirovecii ''Pneumocystis jirovecii'' (previously ''P. carinii'') is a yeast-like fungus of the genus ''Pneumocystis''. The causative organism of ''Pneumocystis'' pneumonia, it is an important human pathogen, particularly among immunocompromised hosts. P ...

'' * '' Proteus mirabilis'' * ''

Proteus vulgaris ''Proteus vulgaris'' is a rod-shaped, nitrate-reducing, indole-positive and catalase-positive, hydrogen sulfide-producing, Gram-negative bacterium that inhabits the intestinal tracts of humans and animals. It can be found in soil, water, and fe ...

'' * ''

Providencia rettgeri ''Providencia rettgeri'' (commonly ''P. rettgeri''), is a Gram negative bacterium that is commonly found in both water and land environments. ''P. rettgeri'' is in the genus Providencia, along with '' Providencia stuartii'', '' Providencia alca ...

'' * ''

Providencia stuartii ''Providencia stuartii'' (commonly ''P. stuartii''), is a Gram negative bacillus that is commonly found in soil, water, and sewage. ''P. stuartii'' is the most common of the 5 species found in the genus Providencia, with '' Providencia rettgeri ...

'' * ''

Salmonella typhi ''Salmonella enterica'' subsp. ''enterica'' is a subspecies of '' Salmonella enterica'', the rod-shaped, flagellated, aerobic, Gram-negative bacterium. Many of the pathogenic serovars of the ''S. enterica'' species are in this subspecies, includi ...

'' (

typhoid fever Typhoid fever, also known as typhoid, is a disease caused by '' Salmonella'' serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over severa ...

) * Non-typhi (

food poisoning Foodborne illness (also foodborne disease and food poisoning) is any illness resulting from the spoilage of contaminated food by pathogenic bacteria, viruses, or parasites that contaminate food, as well as prions (the agents of mad cow disea ...

) ''

Salmonella ''Salmonella'' is a genus of rod-shaped (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two species of ''Salmonella'' are '' Salmonella enterica'' and '' Salmonella bongori''. ''S. enterica'' is the type species and is ...

'' * ''

Serratia ''Serratia'' is a genus of Gram-negative, facultatively anaerobic, rod-shaped bacteria of the family Yersiniaceae. According to the List of Prokaryotic names with Standing Nomenclature (LPSN), there are currently 19 species of ''Serratia'' that a ...

'' spp. * ''

Shigella ''Shigella'' is a genus of bacteria that is Gram-negative, facultative anaerobic, non-spore-forming, nonmotile, rod-shaped, and genetically closely related to '' E. coli''. The genus is named after Kiyoshi Shiga, who first discovered it in ...

'' spp. * ''

Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posit ...

'' * ''

Staphylococcus epidermidis ''Staphylococcus epidermidis'' is a Gram-positive bacterium, and one of over 40 species belonging to the genus '' Staphylococcus''. It is part of the normal human microbiota, typically the skin microbiota, and less commonly the mucosal microbi ...

'' * ''

Staphylococcus saprophyticus ''Staphylococcus saprophyticus'' is a Gram-positive coccus belonging to the genus '' Staphylococcus''. ''S. saprophyticus'' is a common cause of community-acquired urinary tract infections. History ''Staphylococcus saprophyticus'' was not reco ...

'' * ''

Stenotrophomonas maltophilia '' Stenotrophomonas maltophilia'' is an aerobic, nonfermentative, Gram-negative bacterium. It is an uncommon bacterium and human infection is difficult to treat. Initially classified as ''Bacterium bookeri'', then renamed ''Pseudomonas malto ...

'' * '' Streptococcus agalactiae'' * ''

Streptococcus pneumoniae ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic (under aerobic conditions) or beta-hemolytic (under anaerobic conditions), aerotolerant anaerobic member of the genus Streptococcus. They ar ...

'' * ''

Streptococcus pyogenes ''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus '' Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They ...

'' * ''

Streptococcus viridans The viridans streptococci are a large group of commensal streptococcal Gram-positive bacteria species that are α-hemolytic, producing a green coloration on blood agar plates (hence the name "viridans", from Latin "vĭrĭdis", green), although s ...

'' * '' Toxoplasma gondii'' (

) * '' Tropheryma whippelii'' ( Whipple's disease) * ''

Vibrio cholerae ''Vibrio cholerae'' is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimps, and oth ...

'' (

) * ''

Yersinia enterocolitica ''Yersinia enterocolitica'' is a Gram-negative, bacillus-shaped bacterium, belonging to the family Yersiniaceae. It is motile at temperatures of 22–29° C (72–84 °F), but becomes nonmotile at normal human body temperature. ''Y. enterocolit ...

'' * ''

Yersinia pestis ''Yersinia pestis'' (''Y. pestis''; formerly '' Pasteurella pestis'') is a gram-negative, non-motile, coccobacillus bacterium without spores that is related to both ''Yersinia pseudotuberculosis'' and ''Yersinia enterocolitica''. It is a facult ...

'' (

bubonic plague Bubonic plague is one of three types of plague caused by the plague bacterium ('' Yersinia pestis''). One to seven days after exposure to the bacteria, flu-like symptoms develop. These symptoms include fever, headaches, and vomiting, as wel ...

) * ''

Yersinia pseudotuberculosis ''Yersinia pseudotuberculosis'' is a Gram-negative bacterium that causes Far East scarlet-like fever in humans, who occasionally get infected zoonotically, most often through the food-borne route. Animals are also infected by ''Y. pseudotuber ...

'' The only notable nonsusceptible organisms are ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic– facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. a ...

'', the

mycoplasma ''Mycoplasma'' is a genus of bacteria that, like the other members of the class '' Mollicutes'', lack a cell wall around their cell membranes. Peptidoglycan ( murein) is absent. This characteristic makes them naturally resistant to antibioti ...

e and ''

Francisella tularensis ''Francisella tularensis'' is a pathogenic species of Gram-negative coccobacillus, an aerobic bacterium. It is nonspore-forming, nonmotile, and the causative agent of tularemia, the pneumonic form of which is often lethal without treatment. It ...

'' (the causative organism of tularaemia).

Pregnancy and breast feeding

Its use during pregnancy is contraindicated, although it has been placed in Australian pregnancy category C. Its use during the first trimester (during

organogenesis Organogenesis is the phase of embryonic development that starts at the end of gastrulation and continues until birth. During organogenesis, the three germ layers formed from gastrulation (the ectoderm, endoderm, and mesoderm) form the internal org ...

) and 12 weeks prior to pregnancy has been associated with an increased risk of congenital malformations, especially malformations associated with maternal folic acid deficiency (which is most likely related to the mechanism of action of co-trimoxazole) such as neural tube defects such as

spina bifida Spina bifida (Latin for 'split spine'; SB) is a birth defect in which there is incomplete closing of the spine and the membranes around the spinal cord during early development in pregnancy. There are three main types: spina bifida occulta, men ...

, cardiovascular malformations (e.g.

Ebstein's anomaly Ebstein's anomaly is a congenital heart defect in which the septal and posterior leaflets of the tricuspid valve are displaced towards the apex of the right ventricle of the heart. It is classified as a critical congenital heart defect accounting ...

), urinary tract defects, oral clefts, and club foot in epidemiological studies. Its use later on during pregnancy also increases the risk of preterm labour (odds ratio: 1.51) and low birth weight (odds ratio: 1.67). Animal studies have yielded similarly discouraging results. It appears to be safe for use during

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that bre ...

as long as the baby is healthy.

Babies

Its use in those less than 2 months of age is not recommended due to the risk of adverse side effects.

Adverse effects

Common side effects include

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenter ...

, rash, and

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

. Severe

allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...

s and ''Clostridium difficile'' infection may occasionally occur. Its use in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

is not recommended. It appears to be safe for use during

as long as the baby is healthy. Trimethoprim/sulfamethoxazole generally results in bacterial death. It works by blocking the making and use of folate by the microorganisms.

Contraindications

Contraindications include the following: * Known hypersensitivity to trimethoprim, sulphonamides or any other ingredients in the formulations * Pregnancy – especially in the period prior to birth * Severe hepatic failure, marked liver parenchymal damage or jaundice. * Serious haematological disorders and

porphyria Porphyria is a group of liver disorders in which substances called porphyrins build up in the body, negatively affecting the skin or nervous system. The types that affect the nervous system are also known as acute porphyria, as symptoms are ...

(due to the sulfonamide component of the preparation). * Severe

chronic kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...

(CrCl <15 ml/min) where repeated measurements of the plasma concentration cannot be performed * Co-trimoxazole should not be given to neonates during the first 6 weeks, except for the treatment/prophylaxis of ''Pneumocystis jirovecii'' (''P. carinii'') in infants of four weeks of age or greater.

Interactions

Its use is advised against in people being concomitantly treated with: *

ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood volum ...

s like

captopril Captopril, sold under the brand name Capoten among others, is an angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first oral ACE inhibitor found ...

, enalapril, lisinopril, perindopril, and ramipril due to the potential for additive hyperkalaemic effects * Prilocaine — additive risk of

methaemoglobinaemia Methemoglobinemia, or methaemoglobinaemia, is a condition of elevated methemoglobin in the blood. Symptoms may include headache, dizziness, shortness of breath, nausea, poor muscle coordination, and blue-colored skin (cyanosis). Complications m ...

Antiarrhythmics Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a group of pharmaceuticals that are used to suppress abnormally fast rhythms ( tachycardias), such as atrial fibrillation, supraventricular tachycardia and ventricular tac ...

like amiodarone (increased risk of ventricular arrhythmias) and

dofetilide Dofetilide is a class III antiarrhythmic agent. It is marketed under the trade name Tikosyn by Pfizer, and is available in the United States in capsules containing 125, 250, and 500 µg of dofetilide. It is not available in Europe or Australia. ...

(increased risk of QT interval prolongation) * Antibacterials like

dapsone Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. It is a second-line medication for the treatment a ...

(increases plasma levels of both drugs), methenamine (increased risk of crystalluria) and

rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. It is almost always used t ...

(as it may lead to an increased plasma level of rifampicin and lower plasma levels of trimethoprim) * Anticoagulants like

warfarin Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent st ...

and acenocoumarol — anticoagulant effects of either drug is potentiated by this combination *

Sulfonylureas Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...

— effects enhanced *

Phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The in ...

, half-life of phenytoin is increased * Antifolates like pyrimethamine,

proguanil Proguanil, also known as chlorguanide and chloroguanide, is a medication used to treat and prevent malaria. It is often used together with chloroquine or atovaquone. When used with chloroquine the combination will treat mild chloroquine resista ...

and

methotrexate Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...

increase the risk of associated side effects like bone marrow toxicity, folic acid supplementation should be considered. A significant risk of megaloblastic anaemia exists with doses of pyrimethamine in excess of 25 mg/wk. *

Antivirals Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do no ...

, more specifically,

lamivudine Lamivudine, commonly called 3TC, is an antiretroviral medication used to prevent and treat HIV/AIDS. It is also used to treat chronic hepatitis B when other options are not possible. It is effective against both HIV-1 and HIV-2. It is typicall ...

(increased plasma concentrations of lamivudine), zalcitabine (increased plasma concentrations of zalcitabine) and

zidovudine Zidovudine (ZDV), also known as azidothymidine (AZT), is an antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use in combination with other antiretrovirals. It may be used to prevent mother-to-child ...

(increased risk of haematological reactions) * Procainamide and/or

amantadine Amantadine, sold under the brand name Gocovri among others, is a medication used to treat dyskinesia associated with parkinsonism and influenza caused by type A influenzavirus, though its use for the latter is no longer recommended due to wid ...

may have their plasma concentrations increased bilaterally or unilaterally. * Clozapine and other antipsychotics — increased risk of haematological side effects *

Nucleoside Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleoti ...

analogue antineoplastics like azathioprine and

mercaptopurine Mercaptopurine (6-MP), sold under the brand name Purinethol among others, is a medication used for cancer and autoimmune diseases. Specifically it is used to treat acute lymphocytic leukemia (ALL), acute promyelocytic leukemia (APL), Crohn's dis ...

— increased risk of haematological toxicity *

Digoxin Digoxin (better known as Digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is o ...

— increase in digoxin levels in a proportion of elderly patients * Diuretics — elderly patients receiving thiazide diuretics are at a heightened risk for developing thrombocytopaenia while on co-trimoxazole * Ciclosporin — patients who have received a kidney transplant and are receiving co-trimoxazole and ciclosporin concomitantly are at an increased risk of having a reversible deterioration in their kidney function. *

Spironolactone Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood press ...

— concurrent use can increase the likelihood of hyperkalemia, especially in the elderly. The trimethoprim portion acts to prevent potassium excretion in the distal tubule of the nephron. * Potassium aminobenzoate — effects of sulfonamides (like sulfamethoxazole) inhibited. * Laboratory tests — trimethoprim and sulfonamides have been reported to interfere with diagnostic tests, including serum-methotrexate and elevated serum

creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an importa ...

levels, also urea, urinary glucose and urobilinogen tests.

Overdose

Likely signs of toxicity include: * Nausea * Vomiting * Dizziness * Headache * Mental depression * Confusion * Thrombocytopenia *

Uremia Uremia is the term for high levels of urea in the blood. Urea is one of the primary components of urine. It can be defined as an excess of amino acid and protein metabolism end products, such as urea and creatinine, in the blood that would be no ...

* Bone marrow depression * Loss of appetite * Colic * Drowsiness * Unconsciousness The recommended treatment for overdose includes: * Administration of activated charcoal * Stomach pumping * General supportive measures * Haemodialysis, which is moderately effective in clearing co-trimoxazole from the plasma. *

Calcium folinate Calcium is a chemical element with the Symbol (chemistry), symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties ...

treatment in cases of blood dyscrasias * Forcing oral fluids Alkalinisation of the urine may reduce the toxicity of sulfamethoxazole, but it may increase the toxic effects of trimethoprim.

Pharmacology

The

synergy Synergy is an interaction or cooperation giving rise to a whole that is greater than the simple sum of its parts. The term ''synergy'' comes from the Attic Greek word συνεργία ' from ', , meaning "working together". History In Christian ...

between trimethoprim and sulfamethoxazole was first described in the late 1960s. Trimethoprim and sulfamethoxazole have a greater effect when given together than when given separately, because they inhibit successive steps in the

folate synthesis Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

pathway. They are given in a one-to-five ratio in their tablet formulations so that when they enter the body their concentration in the blood and tissues is roughly one-to-twenty — the exact ratio required for a peak synergistic effect between the two. Sulfamethoxazole, a

sulfonamide In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...

, induces its therapeutic effects by interfering with the '' de novo'' (that is, from within the cell) synthesis of folate inside microbial organisms such as protozoa, fungi and bacteria. It does this by competing with ''p''-aminobenzoic acid (PABA) in the biosynthesis of dihydrofolate. Trimethoprim serves as a competitive inhibitor of

dihydrofolate reductase Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as an electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in 1-carbon transfer chemistry ...

(DHFR), hence inhibiting the ''de novo'' synthesis of tetrahydrofolate, the biologically active form of folate. Tetrahydrofolate is crucial in the synthesis of purines, thymidine, and methionine which are needed for the production of DNA and proteins during bacterial replication. Thus the net effect of each of these drugs is a bacteriostatic halt in replication. When combined, TMP and SMX are bactericidal. The effects of trimethoprim causes a backlog of dihydrofolate (DHF) and this backlog can work against the inhibitory effect the drug has on tetrahydrofolate biosynthesis. This is where the sulfamethoxazole comes in; its role is in depleting the excess DHF by preventing it from being synthesised in the first place. Co-trimoxazole was claimed to be more effective than either of its components individually in treating bacterial infections, although this was later disputed. Because it has a higher incidence of adverse effects, including allergic responses, its use has been restricted in many countries to very specific circumstances where its improved efficacy has been demonstrated. It may be effective in a variety of upper and lower respiratory tract infections, kidney and urinary tract infections, gastrointestinal tract infections, skin and wound infections, sepsis, and other infections caused by sensitive organisms. Co-trimoxazole decreases the risk of recurrence of retinochoroiditis. The global problem of advancing antimicrobial resistance has led to a renewed interest in the use of co-trimoxazole more recently.

Society and culture

Legal status

Trade names

Trimethoprim/sulfamethoxazole may be abbreviated as SXT, SMZ-TMP, TMP-SMX, TMP-SMZ, or TMP-sulfa. Co-trimoxazole (

British Approved Name A British Approved Name (BAN) is the official, non-proprietary, or generic name given to a pharmaceutical substance, as defined in the British Pharmacopoeia (BP). The BAN is also the official name used in some countries around the world, because ...

(BAN)) is manufactured and sold by many different companies. The following list of brand names is incomplete: * Bactrim, Bactrimel (manufactured by

Roche F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX ...

and distributed in Europe) * Bactrom (Venezuela) * Bibactin (manufactured by PPM and distributed in Cambodia and some African countries) * Biseptol * Sumetrolim * Co-trimoxazole ( Sandoz) * Cotrim * Deprim (

AFT Pharmaceuticals "Aft", in nautical terminology, is an adjective or adverb meaning towards the stern (rear) of the ship, aircraft or spacecraft, when the frame of reference is within the ship, headed at the fore. For example, "Able Seaman Smith; lie aft!" o ...

) * Diseptyl (Israel) * Graprima Forte Kaplet (manufactured by PT Graha Farma and distributed in Indonesia) * Infectrin, Bactrim (Brazil) * Novo-Trimel * Primotren ( Lek in

Slovenia Slovenia ( ; sl, Slovenija ), officially the Republic of Slovenia (Slovene: , abbr.: ''RS''), is a country in Central Europe. It is bordered by Italy to the west, Austria to the north, Hungary to the northeast, Croatia to the southeast, and ...

and other countries) * Polytrim * Resprim * Sanprima (manufactured by PT Sanbe Farma and distributed in Indonesia) * Septra (

Aspen Pharmacare Aspen Pharmacare Holdings Limited is a public multinational pharmaceutical company headquartered in Durban, South Africa. Founded in 1997, it listed on the Johannesburg Stock Exchange (JSE) in 1998 and purchased South African Druggists in ...

and formerly

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...

) * Septram (Panama) * Septran (GlaxoSmithKline) * Septrin (Spain) * Sulfatrim * Teva-Trimel * Trisul * Vactrim (manufactured and distributed in Laos)

Economics

Trimethoprim/sulfamethoxazole is relatively inexpensive as of 2019.

References

External links

* {{DEFAULTSORT:Trimethoprim Sulfamethoxazole Acetaldehyde dehydrogenase inhibitors Combination antibiotics Pfizer brands GSK plc brands Novartis brands Hoffmann-La Roche brands World Health Organization essential medicines Wikipedia medicine articles ready to translate