Trimethoprim/sulfamethoxazole, sold under the brand name Bactrim among others, is a

fixed-dose combination A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC pr ...

antibiotic 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 Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea. With sulfamethoxazole or dapsone it may be used for ''Pneumocystis'' pneumonia in peo ...

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 human feces, stool (one or more by some definitions, three or more by others) while traveling. It may be accompanied by abdominal cramps, na ...

respiratory tract infections Respiratory tract infections (RTIs) are infectious diseases involving the respiratory tract. An infection of this type usually is further classified as an upper respiratory tract infection (URI or URTI) or a lower respiratory tract infection (LRI ...

, and cholera, 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 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 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 ...

and is also available as a generic medication. 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 splint ...

, like

, or take medicines (such as corticosteroids) 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 ''Acinetobacter'' is a genus of gram-negative bacteria belonging to the wider class of Gammaproteobacteria. ''Acinetobacter'' species are oxidase-negative, exhibit twitching motility, and occur in pairs under magnification. They are importan ...

'' spp. * '' Aeromonas'' 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'' spp. * ''

Bartonella henselae ''Bartonella henselae'', formerly ''Rochalimæa henselae'', is a bacterium that is the causative agent of cat-scratch disease (bartonellosis). ''Bartonella henselae'' is a member of the genus ''Bartonella'', one of the most common types of bacter ...

'' * ''

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 expre ...

'' (

pertussis Whooping cough, also known as pertussis or the 100-day cough, is a highly contagious bacterial disease. Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, but these are followed by two or t ...

) * ''

Brucella ''Brucella'' is a genus of Gram-negative bacteria, named after David Bruce (1855–1931). They are small (0.5 to 0.7 by 0.6 to 1.5 µm), non encapsulated, non motile, facultatively intracellular coccobacilli. ''Brucella'' spp. are the caus ...

'' spp. * '' Burkholderia cepacia'' * ''

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 closely re ...

'' (

glanders Glanders is a contagious zoonotic infectious disease that occurs primarily in horses, mules, and donkeys. It can be contracted by other animals, such as dogs, cats, pigs, goats, and humans. It is caused by infection with the bacterium ''Burkhold ...

) * ''

Burkholderia pseudomallei ''Burkholderia pseudomallei'' (also known as ''Pseudomonas pseudomallei'') is a Gram-negative, bipolar, aerobic, motile rod-shaped bacterium. It is a soil-dwelling bacterium endemic in tropical and subtropical regions worldwide, particularly in T ...

'' (

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 t ...

) * ''

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'' * '' Citrobacter'' 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 t ...

spp.'' * '' Hafnia alvei'' * ''

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 In zoological nomenclature, a type s ...

'' spp. * ''

Klebsiella granulomatis ''Klebsiella granulomatis'' is Gram-negative, rod-shaped bacterium of the genus ''Klebsiella'' known to cause the sexually transmitted disease granuloma inguinale (or donovanosis). It was formerly called ''Calymmatobacterium granulomatis''. It ...

'' * ''

Klebsiella pneumoniae ''Klebsiella pneumoniae'' is a Gram-negative, non-motile, encapsulated, lactose- fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar. Although found in the normal flora of the mo ...

'' * ''

Legionella ''Legionella'' is a genus of pathogenic gram-negative bacteria that includes the species '' L. pneumophila'', causing legionellosis (all illnesses caused by ''Legionella'') including a pneumonia-type illness called Legionnaires' disease and a mil ...

'' spp. * ''

Listeria monocytogenes ''Listeria monocytogenes'' is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the host ...

'' (

listeriosis Listeriosis is a bacterial infection most commonly caused by '' Listeria monocytogenes'', although '' L. ivanovii'' and '' L. grayi'' have been reported in certain cases. Listeriosis can cause severe illness, including severe sepsis, men ...

) * ''

Moraxella catarrhalis ''Moraxella catarrhalis'' is a fastidious, nonmotile, Gram-negative, aerobic, oxidase-positive diplococcus that can cause infections of the respiratory system, middle ear, eye, central nervous system, and joints of humans. It causes the inf ...

'' * '' Morganella morganii'' * '' Mycobacterium tuberculosis'' (

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, i ...

) * '' Neisseria gonorrhoeae'' (

gonorrhoea Gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium ''Neisseria gonorrhoeae''. Infection may involve the genitals, mouth, or rectum. Infected men may experience pain or burning with ur ...

) * ''

Neisseria meningitidis ''Neisseria meningitidis'', often referred to as meningococcus, is a Gram-negative bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life-threatening sepsis. The bacterium is referred to as a ...

'' (

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 a ...

) * '' Nocardia'' spp. * ''

Plesiomonas shigelloides ''Plesiomonas shigelloides'' is a species of bacteria and the only member of its genus. It is a Gram-negative, rod-shaped bacterium which has been isolated from freshwater, freshwater fish, shellfish, cattle, goats, swine, cats, dogs, monkeys, vu ...

'' * ''

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. Pr ...

'' * ''

Proteus mirabilis ''Proteus mirabilis'' is a Gram-negative, facultatively anaerobic, rod-shaped bacterium. It shows swarming motility and urease activity. ''P. mirabilis'' causes 90% of all ''Proteus'' infections in humans. It is widely distributed in soil and ...

'' * ''

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 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'' * ''

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 several ...

) * Non-typhi ( food poisoning) '' Salmonella'' * ''

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 1 ...

'' spp. * '' Staphylococcus aureus'' * '' Staphylococcus epidermidis'' * '' Staphylococcus saprophyticus'' * '' Stenotrophomonas maltophilia'' * ''

Streptococcus agalactiae ''Streptococcus agalactiae'' (also known as group B streptococcus or GBS) is a gram-positive coccus (round bacterium) with a tendency to form chains (as reflected by the genus name ''Streptococcus''). It is a beta- hemolytic, catalase-negative, ...

'' * ''

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'' * ''

Toxoplasma gondii ''Toxoplasma gondii'' () is an obligate intracellular parasitic protozoan (specifically an apicomplexan) that causes toxoplasmosis. Found worldwide, ''T. gondii'' is capable of infecting virtually all warm-blooded animals, but felids, such as d ...

'' (

) * '' Tropheryma whippelii'' (

Whipple's disease Whipple's disease is a rare systemic infectious disease caused by the bacterium '' Tropheryma whipplei''. First described by George Hoyt Whipple in 1907 and commonly considered as a gastrointestinal disorder, Whipple's disease primarily causes ma ...

) * ''

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 ...

'' ( cholera) * ''

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. enterocoliti ...

'' * ''

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) * ''

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. aerug ...

'', the mycoplasmae 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 is ...

'' (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 embryo b ...

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 br ...

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 the ...

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, gastroenteri ...

, 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 derma ...

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

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

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 (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 inhibitors like captopril,

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 furose ...

lisinopril Lisinopril is a medication of the angiotensin-converting enzyme (ACE) inhibitor and is used to treat high blood pressure, heart failure, and after heart attacks. For high blood pressure it is usually a first-line treatment. It is also used t ...

perindopril Perindopril is a medication used to treat high blood pressure, heart failure, or stable coronary artery disease. As a long-acting ACE inhibitor, it works by relaxing blood vessels and decreasing blood volume. As a prodrug, perindopril is hy ...

, and

ramipril Ramipril, sold under the brand name Altace among others, is an ACE inhibitor type medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It can also be used as a preventative medication in patients over 55 yea ...

due to the potential for additive hyperkalaemic effects *

Prilocaine Prilocaine () is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils Löfgren. In its injectable form (trade name Citanest), it is often used in dentistry. It is also often combined with lidocaine as a topical ...

— 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 (VT), ventricular fibrillation (VF), and wide complex tachycardia, as well as atrial fibril ...

(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. I ...

(increased risk of QT interval prolongation) * Antibacterials like dapsone (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, 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 Acenocoumarol is an anticoagulant that functions as a vitamin K antagonist (like warfarin). It is a derivative of coumarin Coumarin () or 2''H''-chromen-2-one is an aromatic organic chemical compound with formula . Its molecule can be descri ...

— anticoagulant effects of either drug is potentiated by this combination * Sulfonylureas — 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 Antifolates are a class of antimetabolite medications that antagonise (that is, block) the actions of folic acid (vitamin B9). Folic acid's primary function in the body is as a cofactor to various methyltransferases involved in serine, methionine ...

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 dise ...

, proguanil and methotrexate increase the risk of associated side effects like

bone marrow toxicity Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (t ...

, 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 Zalcitabine (2′-3′-di deoxycytidine, ddC), also called dideoxycytidine, is a nucleoside analog reverse-transcriptase inhibitor (NRTI) sold under the trade name Hivid. Zalcitabine was the third antiretroviral to be approved by the Food and Drug ...

(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 Procainamide (PCA) is a medication of the antiarrhythmic class used for the treatment of cardiac arrhythmias. It is classified by the Vaughan Williams classification system as class Ia; thus it is a sodium channel blocker of cardiomyocytes. In add ...

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 wi ...

may have their plasma concentrations increased bilaterally or unilaterally. *

Clozapine Clozapine is a psychiatric medication and is the first atypical antipsychotic (also called second-generation antipsychotic). It is primarily used to treat people with schizophrenia and schizoaffective disorders who have had an inadequate respo ...

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 Azathioprine (AZA), sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus, ...

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 — increase in digoxin levels in a proportion of elderly patients *

Diuretics A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics i ...

— elderly patients receiving thiazide diuretics are at a heightened risk for developing

thrombocytopaenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...

while on co-trimoxazole *

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

— 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 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 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, 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 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 (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 Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loca ...

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

Lek Lek or LEK may refer to: * Lek mating, mating in a lek, a type of animal territory in which males of a species gather * Albanian lek, the currency of Albania * Lek (magazine), a Norwegian softcore pornographic magazine * Lek (pharmaceutical comp ...

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, an ...

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 199 ...

and formerly GlaxoSmithKline) * 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