Trimethoprim/sulfamethoxazole, sold under the trade names Bactrim, Cotrim (a short form of the

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 ...

, Co-trimoxazole) and Septra, 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 pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

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 many are beneficial but others can cause infectious diseases. The number of t ...

s. It consists of one part trimethoprim to five parts

sulfamethoxazole Sulfamethoxazole (SMZ or SMX) is an antibiotic. It is used for bacterial infections such as urinary tract infections, bronchitis, and prostatitis and is effective against both gram negative and positive bacteria such as ''Escherichia coli' ...

. It is used to treat urinary tract infections,

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 humans. ...

(MRSA) skin infections, travelers' diarrhea, respiratory tract infections, and

cholera Cholera () is an infection of the small intestine by some Strain (biology), strains of the Bacteria, bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea last ...

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

in people with

HIV/AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...

and other causes of immunosuppression. It can be given orally (swallowed by mouth) or intravenous infusion (slowly injected into a vein with an IV). Trimethoprim/sulfamethoxazole is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. It is 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 ch ...

. In 2022, it was the 143rd most commonly prescribed medication in the United States, with more than 3million prescriptions.

Medical uses

Trimethoprim/sulfamethoxazole generally kills bacteria, by blocking the microorganisms' ability to make and to use folate.

''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 systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

, 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 invo ...

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...

and immunosuppressants) that reduce the body's ability to fight bacterial and viral infections. 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 mul ...

(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'' spp. * '' Alcaligenes''/'' Achromobacter'' spp. * '' Bartonella henselae'' * '' Bordetella pertussis'' (

pertussis Whooping cough ( or ), also known as pertussis or the 100-day cough, is a highly contagious, vaccine-preventable bacterial disease. Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, bu ...

) * ''

Brucella ''Brucella'' is a genus of Gram-negative bacterium, bacteria, named after David Bruce (microbiologist), David Bruce (1855–1931). They are small (0.5 to 0.7 by 0.6 to 1.5 μm), non-Bacterial capsule, encapsulated, non-motile, facultatively ...

'' spp. * '' Burkholderia cepacia'' * '' Burkholderia mallei'' ( glanders) * '' Burkholderia pseudomallei'' ( melioidosis) * ''

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 w ...

'' spp. * '' Chryseobacterium meningosepticum'' * ''

Citrobacter ''Citrobacter'' is a genus of Gram-negative, aerobic, rod-shaped coliform bacteria of the Enterobacteriaceae family. ''Citrobacter'' spp. cause opportunistic infections (including urinary tract infections, gastroenteritis, and bacteremia). ...

'' spp. * ''

Enterobacter ''Enterobacter'' is a genus of common Gram-negative, Facultative anaerobic organism, facultatively anaerobic, bacillus (shape), rod-shaped, non-spore-forming bacteria of the family Enterobacteriaceae. Cultures are found in soil, water, sewage, ...

'' 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 ch ...

'' spp. * ''

Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

'' * '' Haemophilus spp.'' * '' Hafnia alvei'' * '' Kingella'' spp. * '' Klebsiella granulomatis'' * '' Klebsiella pneumoniae'' * ''

Legionella ''Legionella'' is a genus of gram-negative bacteria, gram-negative bacteria that can be seen using a silver stain or grown in a special media that contains cysteine, an amino acid. It is known to cause legionellosis (all illnesses caused by ''Legi ...

'' spp. * '' Listeria monocytogenes'' ( listeriosis) * '' Moraxella catarrhalis'' * '' Morganella morganii'' * ''

Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb), also known as Koch's bacillus, 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'' ha ...

'' (

tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

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

meningococcal disease Meningococcal disease is a serious infection caused by ''Neisseria meningitidis'', also known as meningococcus, a gram negative diplococcus. Meningococcal disease includes meningitis, meningococcal septicemia, or a combination of both, which c ...

) * ''

Nocardia ''Nocardia'' is a genus of weakly staining Gram-positive, catalase, catalase-positive, rod-shaped bacteria. It forms partially acid-fast beaded branching filaments (appearing similar to fungi, but being truly bacteria). It contains a total of 8 ...

'' spp. * '' Plesiomonas shigelloides'' * '' Pneumocystis jirovecii'' * ''

Proteus mirabilis ''Proteus mirabilis'' is a Gram-negative, facultatively Anaerobic organism, anaerobic, rod-shaped bacterium. It shows swarming motility and urease activity. ''P. mirabilis'' causes 90% of all ''Proteus (bacterium), Proteus'' infections in human ...

'' * ''

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 ...

'' * '' Providencia rettgeri'' * '' Providencia stuartii'' * '' Salmonella typhi'' (

typhoid fever Typhoid fever, also known simply as typhoid, is a disease caused by '' Salmonella enterica'' serotype Typhi bacteria, also called ''Salmonella'' Typhi. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often th ...

) * Non-typhi (

food poisoning Foodborne illness (also known as foodborne disease and food poisoning) is any illness resulting from the contamination of food by pathogenic bacteria, viruses, or parasites, as well as prions (the agents of mad cow disease), and toxins such ...

) ''

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

'' * ''

Serratia ''Serratia'' is a genus of Gram-negative, facultatively anaerobic, rod-shaped bacteria of the family Enterobacteriaceae. They are typically 1–5 μm in length, do not produce spores, and can be found in water, soil, plants, and animals. Some mem ...

'' spp. * ''

Shigella ''Shigella'' is a genus of bacteria that is Gram negative, facultatively anaerobic, non–spore-forming, nonmotile, rod shaped, and is genetically nested within ''Escherichia''. The genus is named after Kiyoshi Shiga, who discovered it in 1 ...

'' 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 posi ...

'' * '' Staphylococcus epidermidis'' * '' Staphylococcus saprophyticus'' * '' Stenotrophomonas maltophilia'' * '' Streptococcus agalactiae'' * ''

Streptococcus pneumoniae ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, hemolysis (microbiology), alpha-hemolytic member of the genus ''Streptococcus''. ''S. pneumoniae'' cells are usually found in pairs (diplococci) and do not f ...

'' * ''

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'' * ''

Toxoplasma gondii ''Toxoplasma gondii'' () is a species of parasitic alveolate that causes toxoplasmosis. Found worldwide, ''T. gondii'' is capable of infecting virtually all warm-blooded animals, but members of the cat family (felidae) are the only known d ...

'' (

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

Vibrio cholerae ''Vibrio cholerae'' is a species of Gram-negative bacteria, Gram-negative, Facultative anaerobic organism, facultative anaerobe and Vibrio, comma-shaped bacteria. The bacteria naturally live in Brackish water, brackish or saltwater where they att ...

'' (

) * '' Yersinia enterocolitica'' * ''

Yersinia pestis ''Yersinia pestis'' (''Y. pestis''; formerly ''Pasteurella pestis'') is a Gram-negative bacteria, gram-negative, non-motile bacteria, non-motile, coccobacillus Bacteria, bacterium without Endospore, spores. It is related to pathogens ''Yer ...

'' (

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

) * '' Yersinia pseudotuberculosis'' The only notable nonsusceptible organisms are ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...

'', the mycoplasmae and '' Francisella tularensis'' (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 Neural tube defects (NTDs) are a group of birth defects in which an opening in the spine or cranium remains from early in human development. In the third week of pregnancy called gastrulation, specialized cells on the dorsal side of the embry ...

such as

spina bifida Spina bifida (SB; ; Latin for 'split spine') is a birth defect in which there is incomplete closing of the vertebral column, spine and the meninges, membranes around the spinal cord during embryonic development, early development in pregnancy. T ...

, cardiovascular malformations (e.g. Ebstein's anomaly), 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, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

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. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

vomiting Vomiting (also known as emesis, puking and throwing up) is the 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, gastroenteritis, pre ...

, rash, and

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

. Severe

allergic reaction Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...

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

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

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

as long as the baby is healthy.

Contraindications

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

porphyria Porphyria ( or ) is a group of disorders in which substances called porphyrins build up in the body, adversely affecting the skin or nervous system. The types that affect the nervous system are also known as Porphyria#Acute porphyrias, acute p ...

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

chronic kidney disease Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...

(CrCl <15 ml/min) where repeated measurements of the plasma concentration cannot be performed

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. This class of medicine works by causing relaxation of blood vessels as well as a decr ...

s like

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

enalapril Enalapril, sold under the brand name Vasotec among others, is an ACE inhibitor medication used to treat high blood pressure, diabetic kidney disease, and heart failure. For heart failure, it is generally used with a diuretic, such as furosem ...

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

amiodarone Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia, ventricular fibrillation, and wide complex tachycardia, atrial fibrillation, and paroxys ...

(increased risk of ventricular arrhythmias) and dofetilide (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 an ...

(increases plasma levels of both drugs), methenamine (increased risk of crystalluria) and rifampicin (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. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...

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

Sulfonylureas Sulfonylureas or sulphonylureas are a class of organic compounds used in medicine and agriculture. The functional group consists of a sulfonyl group (-S(=O)2) with its sulphur atom bonded to a nitrogen atom of a ureylene group (N,N-dehydrourea, ...

— effects enhanced * Phenytoin, half-life of phenytoin is increased * Antifolates like

pyrimethamine Pyrimethamine, sold under the brand name Daraprim among others, is a medication used with leucovorin (leucovorin is used to decrease side effects of pyrimethamine; it does not have intrinsic anti-parasitic activity) to treat the parasitic disea ...

, proguanil and

methotrexate Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...

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. Antiviral drugs are a class of antimicrobials ...

, 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 typi ...

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

zidovudine Zidovudine (ZDV), also known as azidothymidine (AZT), was the first 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 mothe ...

(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 because ...

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 nucleotid ...

analogue antineoplastics like azathioprine and mercaptopurine — 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 disease, heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. ...

— 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 Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is taken Oral administration, orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephr ...

— 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 classed as a diuretic medication. It can be used to treat edema, fluid build-up due to hepatic cirrhosis, liver disease or kidney disease. It is also used to reduce risk o ...

— 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 Sulfamethoxazole (SMZ or SMX) is an antibiotic. It is used for bacterial infections such as urinary tract infections, bronchitis, and prostatitis and is effective against both gram negative and positive bacteria such as ''Escherichia coli' ...

) 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 impor ...

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 condition of having high levels of urea in the blood. Urea is one of the primary components of urine. It can be defined as an excess in the blood of amino acid and protein metabolism end products, such as urea and creatinine, which ...

* 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 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 (i.e., a non-linear addition of force, energy, or effect). The term ''synergy'' comes from the Attic Greek word συνεργία ' f ...

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 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 Chemical structure, structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this gro ...

, 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 (DHFR), hence inhibiting the ''de novo'' synthesis of tetrahydrofolate, the biologically active form of folate. Tetrahydrofolate is crucial in the synthesis of

purine Purine is a heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted puri ...

thymidine Thymidine (nucleoside#List of nucleosides and corresponding nucleobases, symbol dT or dThd), also known as deoxythymidine, deoxyribosylthymine, or thymine deoxyriboside, is a pyrimidine nucleoside, deoxynucleoside. Deoxythymidine is the DNA nuc ...

, and

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other non-essential amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine play ...

which are needed for the production of DNA and proteins during bacterial replication. 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.

Society and culture

Legal status

Brand names

Trimethoprim/sulfamethoxazole may be abbreviated as SXT, SMZ-TMP, TMP-SMX, TMP-SMZ, or TMP-sulfa. The generic

(BAN) Co-trimoxazole is used for trimethoprim/sulfamethoxazole 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 Switzerland, Swiss multinational corporation, multinational holding healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, ...

and distributed in Europe) * Bactrom (Venezuela) * Bibactin (manufactured by PPM and distributed in Cambodia and some African countries) * Biseptol * Sumetrolim * Co-trimoxazole (used as generic UK name) * Cotrim * Deprim ( AFT Pharmaceuticals) * Diseptyl (Israel) * Graprima Forte Kaplet (manufactured by PT Graha Farma and distributed in Indonesia) * Infectrin, Bactrim (Brazil) * Novo-Trimel * Primadex (manufactured by Dexa Medica and distributed in Indonesia) * Primotren ( Lek in

Slovenia Slovenia, officially the Republic of Slovenia, is a country in Central Europe. It borders Italy to the west, Austria to the north, Hungary to the northeast, Croatia to the south and southeast, and a short (46.6 km) coastline within the Adriati ...

and other countries) * Resprim * Sanprima (manufactured by Sanbe Farma and distributed in Indonesia) * Septra ( Aspen Pharmacare and formerly

GlaxoSmithKline GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...

) * 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

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