Browse history interactively

Page 1

Page 1Revision 1

Page 2

Page 2Revision 2

← Previous editContent deleted Content addedVisualWikitext

Revision as of 19:12, 3 October 2010 editChowbok (talk | contribs)Autopatrolled, Extended confirmed users, File movers, Pending changes reviewers, Rollbackers48,092 editsm clean up using AWB (7159)← Previous edit		Latest revision as of 23:15, 21 January 2025 edit undoRickyCourtney (talk | contribs)Extended confirmed users, Pending changes reviewers47,259 editsm Fix links, references edited with ProveIt #proveit, script-assisted date audit and style fixes per MOS:NUMTag: ProveIt edit
(474 intermediate revisions by more than 100 users not shown)
Line 1:		Line 1:
			{{Short description|Combination of two antibiotic drugs}}
	{{drugbox
			{{Use dmy dates|date=January 2025}}
	| type = combo
			{{cs1 config |name-list-style=vanc |display-authors=6}}
	| component1 = Trimethoprim
			{{Infobox drug
	| class1 = ] ] (16.7%)
			| verifiedrevid = 388518461
	| component2 = Sulfamethoxazole
			| type = combo
	| class2 = ] (83.3%)
	| image = Co-trimoxazole.JPG		| image = Trimethoprim and sulfamethoxazole.svg
			| image_class = skin-invert-image
			| width = 200
			| alt =
			| caption = Trimethoprim (top) and sulfamethoxazole (bottom)
			| BAN = Co-trimoxazole
			<!-- Combo data -->
			| component1 = Sulfamethoxazole
			| class1 = ]
			| component2 = Trimethoprim
			| class2 = ] ]
			<!-- Clinical data -->
			| tradename = Bactrim, Cotrim, Septra, ]
			| Drugs.com = {{drugs.com|monograph|co-trimoxazole}}
			| MedlinePlus =
			| DailyMedID = Sulfamethoxazole trimethoprim
			| pregnancy_AU = C
			| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{Cite web |date=8 March 2019 |title=Sulfamethoxazole / trimethoprim Use During Pregnancy |url=https://www.drugs.com/pregnancy/sulfamethoxazole-trimethoprim.html |url-status=live |archive-url=https://web.archive.org/web/20150906073951/http://www.drugs.com/pregnancy/sulfamethoxazole-trimethoprim.html |archive-date=6 September 2015 |access-date=15 April 2020 |website=Drugs.com}}</ref>
			| pregnancy_category =
			| routes_of_administration = ], ]<ref name="AHFS2015" />
			| ATC_prefix = J01
			| ATC_suffix = EE01
			| ATC_supplemental = {{ATC|J04|AM08}}
			<!-- Legal status -->
			| legal_AU = S4
			| legal_AU_comment = <ref name="TGA">{{Cite web |title=Bactrim DS tablet blister pack |url=https://tga-search.clients.funnelback.com/s/search.html?collection=tga-artg&profile=record&meta_i=162563 |url-status=live |archive-url=https://web.archive.org/web/20211229045805/https://tga-search.clients.funnelback.com/s/search.html?collection=tga-artg&profile=record&meta_i=162563 |archive-date=29 December 2021 |access-date=28 December 2021 |website=Therapeutic Goods Administration (TGA)}}</ref><ref>{{Cite web |title=TGA eBS – Product and Consumer Medicine Information Licence |url=http://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2021-PI-01633-1 |url-status=live |archive-url=https://web.archive.org/web/20211229045813/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2021-PI-01633-1 |archive-date=29 December 2021 |access-date=29 December 2021}}</ref>
			| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
			| legal_BR_comment =
			| legal_CA = Rx-only
			| legal_CA_comment =
			| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
			| legal_DE_comment =
			| legal_NZ = <!-- Class A, B, C -->
			| legal_NZ_comment =
			| legal_UK = POM
			| legal_UK_comment = <ref name="Co-Trimoxazole SmPC">{{Cite web |date=1 August 2021 |title=Co-Trimoxazole 80 mg/400 mg Tablets – Summary of Product Characteristics (SmPC) |url=https://www.medicines.org.uk/emc/product/6999/smpc |url-status=live |archive-url=https://web.archive.org/web/20211229045804/https://www.medicines.org.uk/emc/product/6999/smpc |archive-date=29 December 2021 |access-date=28 December 2021 |website=(emc)}}</ref>
			| legal_US = Rx-only
			| legal_US_comment = <ref name="Bactrim FDA label">{{Cite web |title=Bactrim DS- sulfamethoxazole and trimethoprim tablet Bactrim- sulfamethoxazole and trimethoprim tablet |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f59d0c04-9c66-4d53-a0e1-cb55570deb62 |url-status=live |archive-url=https://web.archive.org/web/20211229045803/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f59d0c04-9c66-4d53-a0e1-cb55570deb62 |archive-date=29 December 2021 |access-date=28 December 2021 |website=DailyMed}}</ref>
			| legal_EU =
			| legal_EU_comment =
			| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
			| legal_UN_comment =
			| legal_status = <!-- For countries not listed above -->
			<!-- Identifiers -->
			| CAS_number_Ref =
			| CAS_number = 8064-90-2
			| CAS_supplemental =
			| PubChem = 358641
			| IUPHAR_ligand =
			| DrugBank =
			| ChemSpiderID_Ref =
	| ChemSpiderID = 318412		| ChemSpiderID = 318412
			| UNII_Ref =
	| InChI = 1/C14H18N4O3.C10H11N3O3S/c1-19-10-5-8(6-11(20-2)12(10)21-3)4-9-7-17-14(16)18-13(9)15;1-7-6-10(12-16-7)13-17(14,15)9-4-2-8(11)3-5-9/h5-7H,4H2,1-3H3,(H4,15,16,17,18);2-6H,11H2,1H3,(H,12,13)
			| UNII =
	| smiles = O=S(=O)(Nc1noc(c1)C)c2ccc(N)cc2.O(c1cc(cc(OC)c1OC)Cc2cnc(nc2N)N)C
			| KEGG_Ref =
	| InChIKey = WZRJTRPJURQBRM-UHFFFAOYAV
			| KEGG = D00285
	| CAS_number = 8064-90-2
			| ChEBI_Ref =
	| ATC_prefix = J01
			| ChEBI = 3770
	| ATC_suffix = EE01
			| ChEMBL_Ref =
	| PubChem = 358641
			| ChEMBL = 58061
	| DrugBank =
			| NIAID_ChemDB =
	| pregnancy_AU = C
			| PDB_ligand =
	| pregnancy_US = C
			| synonyms = TMP/SMX <!-- cotrimoxazole listed under BAN-->
	| pregnancy_category=
	| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
	| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
	| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
	| legal_US = Rx-only
	| legal_status =
	| routes_of_administration = Oral
	}}		}}
	'''Co-trimoxazole''' (abbreviated SXT, TMP-SMX, TMP-SMZ or TMP-sulfa) is a ] ] combination of ] and ], in the ratio of 1 to 5, used in the treatment of a variety of bacterial infections. The name co-trimoxazole is the ], and has been marketed worldwide under many ]s including '''Septra''' (]), '''Bactrim''' (]), and various ] preparations. Sources differ as to whether co-trimoxazole usually is ] or ].
			<!-- Definition and medical uses -->
	==Synergistic action==
			'''Trimethoprim/sulfamethoxazole''', sold under the trade names '''Bactrim''', '''Cotrim''' (a short form of the ], '''Co-trimoxazole''') and '''Septra''', among others, is a ] ] medication used to treat a variety of ]s.<ref name="AHFS2015">{{Cite web |title=Co-trimoxazole |url=https://www.drugs.com/monograph/co-trimoxazole.html |url-status=live |archive-url=https://web.archive.org/web/20150906003435/http://www.drugs.com/monograph/co-trimoxazole.html |archive-date=6 September 2015 |access-date=1 August 2015 |publisher=The American Society of Health-System Pharmacists}}</ref> It consists of one part ] to five parts ].<ref name="Ric2015" /> It is used to treat ], ] (MRSA) skin infections, ], ], and ], among others.<ref name="AHFS2015" /><ref name="Ric2015" /> It is used both to treat and prevent ] and ] in people with ] and other causes of immunosuppression.<ref name="AHFS2015" /> It can be given ] (swallowed by mouth) or ] (slowly injected into a vein with an IV).<ref name="AHFS2015" />
	The ] between ] and ] was first described in a series of '']'' and '']'' experiments published in the late 1960s.<ref>{{cite journal|author=Bushby SRM, Hitchings GH|title=Trimethoprim, a sulphonamide potentiator|journal=Brit J Pharmacol|volume=33|pages=72|year=1968|pmid=5301731|issue=1|pmc=1570262}}</ref><ref>{{cite journal|author=Böhni E|title=Vergleichende bakteriologische untersuchungen mit der Kombination Trimethoprim/Sulfamethoxazole in vitro und in vivo|journal=Chemotherapy|volume=14|issue=Suppl|pages=1|year=1969|doi=10.1159/000220651|pmid=4908562}}</ref><ref>{{cite journal|author=Böhni E|title=Chemotherapeutic activity of the combination of trimethoprim and sulfamethoxazole in infections of mice|journal=Postgrad Med J|year=1969|volume=45|issue=Suppl|pages=18|pmid=4902845}}</ref> Trimethoprim and sulfamethoxazole have a greater effect when given together than when given separately; the reason is because they inhibit successive steps in the ] synthesis pathway (see diagram below).
			<!-- Society and culture -->
	It is unclear whether this synergy occurs at doses used in humans,<ref>{{cite journal |author=Brumfitt W, Hamilton-Miller JM |title=Limitations of and indications for the use of co-trimoxazole | journal=J Chemother |year=1994 |month=February |volume=6 |issue=1 |pages=3–11 |pmid=8071675}}</ref> because, at the concentrations seen in blood and tissues, the ratio of trimethoprim to sulphamethoxazole is 1:20,<ref>{{cite journal|author=Kremers P, Duvivier J, Heusghem C|title=Pharmacokinetic studies of co-trimoxazole in man after single and repeated doses|journal=J Clin Pharmacol|year=1974|volume=14|pages=112&ndash;117}}</ref> which is less than the 1:5 ratio needed ''in vitro'' for synergy to occur.
			Trimethoprim/sulfamethoxazole is on the ].<ref name="WHO23rd">{{Cite book |author-link=World Health Organization |title=The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) |vauthors=((World Health Organization)) |publisher=World Health Organization |year=2023 |location=Geneva |hdl=10665/371090 |id=WHO/MHP/HPS/EML/2023.02 |hdl-access=free}}</ref> It is available as a ].<ref name="Ric2015">{{Cite book |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition |vauthors=Hamilton R |date=2015 |publisher=Jones & Bartlett Learning |isbn=978-1-284-05756-0 |page=105}}</ref><ref name="Brown2019" /> In 2022, it was the 143rd most commonly prescribed medication in the United States, with more than 3{{nbsp}}million prescriptions.<ref>{{Cite web |title=The Top 300 of 2022 |url=https://clincalc.com/DrugStats/Top300Drugs.aspx |url-status=live |archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx |archive-date=30 August 2024 |access-date=30 August 2024 |website=ClinCalc}}</ref><ref>{{Cite web |title=Sulfamethoxazole; Trimethoprim Drug Usage Statistics, United States, 2013–2022 |url=https://clincalc.com/DrugStats/Drugs/SulfamethoxazoleTrimethoprim |access-date=30 August 2024 |website=ClinCalc}}</ref>
			== Medical uses ==
	<center>]</center>
			Trimethoprim/sulfamethoxazole generally kills bacteria, by blocking the microorganisms' ability ] and ].<ref name="AHFS2015" />
			=== ''Pneumocystis jirovecii'' pneumonia ===
	Sulfamethoxazole acts as a false-substrate inhibitor of ]. ] such as sulfamethoxazole are analogues of ] (PABA) and, thus, are ]s of the enzyme, inhibiting the production of ].
			Trimethoprim/sulfamethoxazole (TMP/SMX) is the medicine most commonly used to prevent ] (PCP)<ref name="cdc.gov">{{Cite web |date=13 October 2021 |title=Pneumocystis pneumonia |url=https://www.cdc.gov/fungal/diseases/pneumocystis-pneumonia/index.html |url-status=live |archive-url=https://web.archive.org/web/20210726083526/https://www.cdc.gov/fungal/diseases/pneumocystis-pneumonia/index.html |archive-date=26 July 2021 |access-date=30 December 2021 |website=U.S. ] (CDC)}}</ref> People who get ''Pneumocystis'' pneumonia have a medical condition that weakens their ], like ], or take medicines (such as ], ] and ]s) that reduce the body's ability to fight ] and ]. People with HIV/AIDS are less likely to get ''Pneumocystis'' pneumonia as a result of ] (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.<ref name="cdc.gov" />
			=== Susceptibility ===
	Trimethoprim acts by interfering with the action of bacterial ], inhibiting synthesis of tetrahydrofolic acid.
			Organisms against which trimethoprim/sulfamethoxazole can be effective include:<ref name="MSR">{{Cite web |title=trimethoprim/sulfamethoxazole (Rx) |url=http://reference.medscape.com/drug/bactrim-trimethoprim-sulfamethoxazole-342543#showall |url-status=live |archive-url=https://web.archive.org/web/20140116124927/http://reference.medscape.com/drug/bactrim-trimethoprim-sulfamethoxazole-342543#showall |archive-date=16 January 2014 |access-date=13 January 2014 |website=Medscape Reference}}</ref><ref name="Drugs" />
			{{div col|colwidth=20em}}
			* '']'' spp.
			* '']'' spp.
			* '']''/'']'' spp.
			* '']''
			* '']'' (])
			* '']'' spp.
			* '']''
			* '']'' (])
			* '']'' (])
			* '']'' spp.
			* '']''
			* '']'' spp.
			* '']'' spp.
			* '']'' spp.
			* '']''
			* ''] spp.''
			* '']''
			* '']'' spp.
			* '']''
			* '']''
			* '']'' spp.
			* '']'' (])
			* '']''
			* '']''
			* '']'' (])
			* '']'' (])
			* '']'' (])
			* '']'' spp.
			* '']''
			* '']''
			* '']''
			* '']''
			* '']''
			* '']''
			* '']'' (])
			* Non-typhi (]) '']''
			* '']'' spp.
			* '']'' spp.
			* '']''
			* '']''
			* '']''
			* '']''
			* '']''
			* '']''
			* '']''
			* '']''
			* '']'' (])
			* '']'' (])
			* '']'' (])
			* '']''
			* '']'' (])
			* '']''
			{{div col end}}
			The only notable nonsusceptible organisms are '']'', the ]e<ref name="Drugs" /> and '']'' (the causative organism of ]).<ref>{{Cite web |date=17 July 2011 |title=Tularemia |url=http://new.dhh.louisiana.gov/assets/oph/Center-PHCH/Center-CH/infectious-epi/EpiManual/TularemiaManual.pdf |url-status=live |archive-url=https://web.archive.org/web/20140223030105/http://new.dhh.louisiana.gov/assets/oph/Center-PHCH/Center-CH/infectious-epi/EpiManual/TularemiaManual.pdf |archive-date=23 February 2014 |access-date=12 February 2014 |website=Infectious Disease Epidemiology Section |publisher=Louisiana Office of Public Health}}</ref><ref>{{Cite journal |vauthors=Harik NS |date=July 2013 |title=Tularemia: epidemiology, diagnosis, and treatment |journal=Pediatric Annals |volume=42 |issue=7 |pages=288–292 |doi=10.3928/00904481-20130619-13 |pmid=23805970}}</ref>
	] is an essential precursor in the '']'' synthesis of the DNA ]s ] and ]. Bacteria are unable to take up folic acid from the environment (i.e., the infection host) and, thus, are dependent on their own de novo synthesis - inhibition of the enzyme starves the bacteria of two bases necessary for ] and ].
			=== Pregnancy and breast feeding ===
	==Clinical indications==
			Its use during pregnancy is contraindicated, although it has been placed in Australian pregnancy category C.<ref name="MSR" /> Its use during the first trimester (during ]) 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 ] such as ], cardiovascular malformations (e.g. ]), urinary tract defects, oral clefts, and club foot in epidemiological studies.<ref name="MSR" /> 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).<ref>{{Cite journal |vauthors=Yang J, Xie RH, Krewski D, Wang YJ, Walker M, Wen SW |date=May 2011 |title=Exposure to trimethoprim/sulfamethoxazole but not other FDA category C and D anti-infectives is associated with increased risks of preterm birth and low birth weight |journal=International Journal of Infectious Diseases |volume=15 |issue=5 |pages=e336–e341 |doi=10.1016/j.ijid.2011.01.007 |pmid=21345707 |doi-access=free |title-link=doi}}</ref><ref>{{Cite journal |vauthors=Santos F, Sheehy O, Perreault S, Ferreira E, Berard A |date=October 2011 |title=Exposure to anti-infective drugs during pregnancy and the risk of small-for-gestational-age newborns: a case-control study |journal=BJOG |volume=118 |issue=11 |pages=1374–1382 |doi=10.1111/j.1471-0528.2011.03041.x |pmid=21749628 |s2cid=21014782 |doi-access=free |title-link=doi}}</ref> Animal studies have yielded similarly discouraging results.<ref name="TGA" />
	Co-trimoxazole was claimed to be more effective than either of its components individually in treating bacterial infections, although this was later disputed.<ref>{{cite journal |author=Brumfitt W, Hamilton-Miller JM |title=Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines | journal=J Chemother |year=1993 |month=December |volume=5 |issue=6 |pages=465–9 |pmid=8195839}}</ref> Along with its associated greater incidence of adverse effects including allergic responses (see below), its widespread use has been restricted in many countries to very specific circumstances where its improved efficacy is demonstrated.<ref>{{cite journal |author= |title=Co-trimoxazole use restricted |journal=Drug Ther Bull |year=1995 |month=December | volume=33 |issue=12 |pages=92–3 |pmid=8777892 |doi=10.1136/dtb.1995.331292}}</ref> It may be effective in a variety of upper and lower ] infections, ] and ], ] infections, skin and wound infections, ]s and other infections caused by sensitive organisms. The global problem of advancing antimicrobial resistance has led to a renewed interest in the use of co-trimoxazole in various settings more recently.<ref>{{cite journal |author=Falagas ME, Grammatikos AP, Michalopoulos A |title=Potential of old-generation antibiotics to address current need for new antibiotics |journal=Expert Rev Anti Infect Ther |volume=6 |issue=5 |pages=593–600 |year=2008 |month=October |pmid=18847400 |doi=10.1586/14787210.6.5.593}}</ref>
			It appears to be safe for use during ] as long as the baby is healthy.<ref name="Preg2015">{{Cite web |title=Sulfamethoxazole / trimethoprim Pregnancy and Breastfeeding Warnings |url=https://www.drugs.com/pregnancy/sulfamethoxazole-trimethoprim.html |url-status=live |archive-url=https://web.archive.org/web/20150906073951/http://www.drugs.com/pregnancy/sulfamethoxazole-trimethoprim.html |archive-date=6 September 2015 |access-date=31 August 2015 |quote=An extensive systematic review of sulfonamide usage near term and during breastfeeding found no side effects in infants; the authors concluded that use of this combination drug during breastfeeding presents no risk of neonatal kernicterus... LactMed: Use is considered acceptable when breastfeeding healthy, full-term infants after the newborn period}}</ref>
	Specific indications for its use include:
	===HIV===		=== Babies ===
			Its use in those less than 2 months of age is not recommended due to the risk of adverse side effects.<ref>{{Cite web |title=Drugs & Medications |url=https://www.webmd.com/drugs/2/drug-5530/bactrim-ds-oral/details/list-sideeffects |url-status=live |archive-url=https://web.archive.org/web/20190419210051/https://www.webmd.com/drugs/2/drug-5530/bactrim-ds-oral/details/list-sideeffects |archive-date=19 April 2019 |access-date=19 April 2019 |website=WebMD}}</ref>
	Being an antibiotic, co-trimoxazole does not have any activity against HIV itself, but it is often prescribed to immunocompromised patients as ] pneumonia prophylaxis.
			== Adverse effects ==
	===Bacterial===
			{{See also|List of side effects of trimethoprim/sulfamethoxazole}}
	*infections caused by ''] monocytogenes'', ''Nocardia'' spp., ''] maltophilia'' (''Zanthomonas maltophilia'')
	*] infections presenting as ] or ]
	*]
	*]
	*]
	*]
			Common side effects include ], ], rash, and ].<ref name="AHFS2015" /> Severe ]s and ] may occasionally occur.<ref name="AHFS2015" /> Its use in ] is not recommended.<ref name="AHFS2015" /><ref name="Preg2015" /> It appears to be safe for use during ] as long as the baby is healthy.<ref name="Preg2015" />
	===Protozoan===
	*]<ref name="pmid18257775">{{cite journal |author=Lagrange-Xélot M, Porcher R, Sarfati C, ''et al'' |title=Isosporiasis in patients with HIV infection in the highly active antiretroviral therapy era in France |journal=HIV Med. |volume=9 |issue=2 |pages=126–30 |year=2008 |month=February |pmid=18257775 |doi=10.1111/j.1468-1293.2007.00530.x |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1464-2662&date=2008&volume=9&issue=2&spage=126}}</ref>
	*prophylaxis of cerebral ] in ] patients
	* ]
			== Contraindications ==
	===Fungal===
			Contraindications include the following:<ref name="MSR" /><ref name="Co-Trimoxazole SmPC" />
	*treatment and prophylaxis of pneumonia caused by '']'' (formerly identified as ''P. carinii'' and commonly seen in immunocompromised patients including those suffering from cancer or ]/])
			{{div col|colwidth=36em}}
	{{Refimprove|date=September 2008}}
			* 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 ] (due to the sulfonamide component of the preparation).
			* Severe ] (CrCl <15 ml/min) where repeated measurements of the plasma concentration cannot be performed
			{{div col end}}
	==Safety==		== Interactions ==
			Its use is advised against in people being concomitantly treated with:<ref name="MSR" /><ref name="TGA" /><ref name="Co-Trimoxazole SmPC" /><ref name="Bactrim FDA label" /><ref name="BNF">{{Cite book |last=Joint Formulary Committee |url=https://archive.org/details/bnf65britishnati0000unse |title=British National Formulary (BNF) |publisher=Pharmaceutical Press |year=2013 |isbn=978-0-85711-084-8 |edition=65 |location=London, UK |url-access=registration}}</ref><ref name="AMH">{{Cite book |title=Australian Medicines Handbook |publisher=The Australian Medicines Handbook Unit Trust |year=2013 |isbn=978-0-9805790-9-3 |veditors=Rossi S |edition=2013 |location=Adelaide}}</ref>
	There has been some concern about its use, however, since it has been associated with both frequent mild allergic reactions and serious adverse effects including ], ], ], ], as well as severe liver damage (cholestatic hepatosis, hepatitis, liver necrosis, fulminant liver failure).{{Citation needed|date=September 2008}} Due to displacement of bilirubin from albumin, there is an increased risk of ] in the newborn during the last 6 weeks of pregnancy. Also renal impairment up to acute renal failure and anuria have been reported. These side-effects are seen especially in the elderly and may be fatal. (Joint Formulary Committee, 2004). Both Folic acid and Folinic acid were found equally effective in reducing the adverse effects of TMP-SMX, so unless new evidence is found for Folinic acid that shows it is more effective than the cheaper Folic acid, Folic acid will continue to be the preferred treatment method.
			{{div col|colwidth=36em}}
	In some countries, co-trimoxazole has been withdrawn due to these toxic effects.{{Citation needed|date=September 2008}}
			* ]s like ], ], ], ], and ] due to the potential for additive ] effects<ref name="Co-Trimoxazole SmPC" />
			* ] — additive risk of ]
			* ] like ] (increased risk of ventricular arrhythmias) and ] (increased risk of QT interval prolongation)
			* Antibacterials like ] (increases plasma levels of both drugs), ] (increased risk of crystalluria) and ] (as it may lead to an increased plasma level of rifampicin and lower plasma levels of trimethoprim)
			* Anticoagulants like ] and ] — anticoagulant effects of either drug is potentiated by this combination
			* ] — effects enhanced
			* ], half-life of phenytoin is increased
			* ] like ], ] and ] increase the risk of associated side effects like ], folic acid supplementation should be considered. A significant risk of megaloblastic anaemia exists with doses of pyrimethamine in excess of 25&nbsp;mg/wk.
			* ], more specifically, ] (increased plasma concentrations of lamivudine), ] (increased plasma concentrations of zalcitabine) and ] (increased risk of haematological reactions)
			* ] and/or ] may have their plasma concentrations increased bilaterally or unilaterally.
			* ] and other antipsychotics — increased risk of haematological side effects
			* ] analogue antineoplastics like ] and ] — increased risk of haematological toxicity
			* ] — increase in digoxin levels in a proportion of elderly patients
			* ] — elderly patients receiving thiazide diuretics are at a heightened risk for developing ] while on co-trimoxazole
			* ] — 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.
			* ] — 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.<ref name="pmid24156179">{{Cite journal |vauthors=Juvet T, Gourineni VC, Ravi S, Zarich SW |date=September 2013 |title=Life-threatening hyperkalemia: a potentially lethal drug combination |journal=Connecticut Medicine |volume=77 |issue=8 |pages=491–3 |pmid=24156179}}</ref>
			* Potassium aminobenzoate — effects of sulfonamides (like ]) inhibited.
			* Laboratory tests — trimethoprim and sulfonamides have been reported to interfere with diagnostic tests, including serum-methotrexate and elevated serum ] levels,<ref name="Gentry_2013">{{Cite journal |vauthors=Gentry CA, Nguyen AT |date=December 2013 |title=An evaluation of hyperkalemia and serum creatinine elevation associated with different dosage levels of outpatient trimethoprim-sulfamethoxazole with and without concomitant medications |journal=The Annals of Pharmacotherapy |volume=47 |issue=12 |pages=1618–26 |doi=10.1177/1060028013509973 |pmid=24259630 |s2cid=19395548}}</ref> also urea, urinary glucose and urobilinogen tests.
			{{div col end}}
			=== Overdose ===
	Thus the current ] Committee on Safety of Medicines (CSM) guidelines recommend limiting its use to:{{Citation needed|date=September 2008}}
			Likely signs of toxicity include:<ref name="TGA" />
	*]
			{{div col|colwidth=14em}}
	*] and ]
			* Nausea
	*acute exacerbations of chronic bronchitis and infections of the urinary tract where there is good rationale for use
			* Vomiting
	*acute ] in children where there is good rationale
			* Dizziness
			* Headache
			* Mental depression
			* Confusion
			* Thrombocytopenia
			* ]
			* Bone marrow depression
			* Loss of appetite
			* Colic
			* Drowsiness
			* Unconsciousness
			{{div col end}}
			The recommended treatment for overdose includes:<ref name="TGA" />
	==Trade names==
			* Administration of activated charcoal
	Co-trimoxazole is manufactured and sold by many different companies. Some of the brand names are listed here, but this list is not complete.
			* Stomach pumping
	*Bactrim, Bactrimel (])
			* General supportive measures
	*Cotrim
			* Haemodialysis, which is moderately effective in clearing co-trimoxazole from the plasma.
	*Septrin, Septra (] and formerly ])
			* ] treatment in cases of blood dyscrasias
	*Sulfatrim
			* Forcing oral fluids
	*Biseptol
			Alkalinisation of the urine may reduce the toxicity of sulfamethoxazole, but it may increase the toxic effects of trimethoprim.<ref name="TGA" />
	==References==		== Pharmacology ==
			]
	* Rossi S, editor. ] 2004. Adelaide: Australian Medicines Handbook; 2004. ISBN 0-9578521-4-2.
	* ], 51st edition (April 20, 2006). London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2006. ISBN 0-85369-668-3
	* Newspaper campaign over adverse events; 1994-
			The ] between trimethoprim and sulfamethoxazole was first described in the late 1960s.<ref>{{Cite journal |vauthors=Bushby SR, Hitchings GH |date=May 1968 |title=Trimethoprim, a sulphonamide potentiator |journal=British Journal of Pharmacology and Chemotherapy |volume=33 |issue=1 |pages=72–90 |doi=10.1111/j.1476-5381.1968.tb00475.x |pmc=1570262 |pmid=5301731}}</ref><ref>{{Cite journal |vauthors=Böhni E |year=1969 |title= |journal=Chemotherapy |volume=14 |issue=Suppl |pages=Suppl:1–Suppl21 |doi=10.1159/000220651 |pmid=4908562}}</ref><ref>{{Cite journal |vauthors=Böhni E |date=November 1969 |title=Chemotherapeutic activity of the combination of trimethoprim and sulphamethoxazole in infections of mice |journal=Postgraduate Medical Journal |volume=45 |issue=Suppl |pages=Suppl:18–Suppl:21 |pmid=4902845}}</ref> Trimethoprim and sulfamethoxazole have a greater effect when given together than when given separately, because they inhibit successive steps in the ] 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.<ref name="Drugs" />
	== Footnotes==
	{{reflist}}
			Sulfamethoxazole, a ], induces its therapeutic effects by interfering with the '']'' (that is, from within the cell) synthesis of folate inside microbial organisms such as protozoa, fungi and bacteria. It does this by competing with ] (PABA) in the biosynthesis of dihydrofolate.<ref name="Drugs" />
			Trimethoprim serves as a competitive inhibitor of ] (DHFR), hence inhibiting the ''de novo'' synthesis of tetrahydrofolate, the biologically active form of folate.<ref name="Drugs" />
			Tetrahydrofolate is crucial in the synthesis of ]s, ], and ] which are needed for the production of DNA and proteins<ref>{{Cite web |title=Tetrahydrofolic acid |url=https://pubchem.ncbi.nlm.nih.gov/compound/tetrahydrofolate#section=Drug-and-Medication-Information |url-status=live |archive-url=https://web.archive.org/web/20180226151952/https://pubchem.ncbi.nlm.nih.gov/compound/tetrahydrofolate#section=Drug-and-Medication-Information |archive-date=26 February 2018 |access-date=26 February 2018 |website=PubChem |publisher=U.S. National Library of Medicine}}</ref> 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.<ref name="Drugs" />
			Co-trimoxazole was claimed to be more effective than either of its components individually in treating bacterial infections, although this was later disputed.<ref>{{Cite book |url=https://www.taylorfrancis.com/books/edit/10.1201/9781498747967/kucers-use-antibiotics-lindsay-grayson-sara-cosgrove-suzanne-crowe-lindsay-grayson-william-hope-james-mccarthy-john-mills-johan-mouton-david-paterson |title=Kucers' the Use of Antibiotics |vauthors=Trubiano JA, Grayson ML |publisher=CRC Press |year=2017 |isbn=978-1-4987-4796-7 |veditors=Grayson ML, Cosgrove S, Crowe S, Hope W, McCarthy J, Mills J, Mouton JW, Paterson D |edition=7th |pages=1625, 1634 |chapter=Trimethoprim and Trimethoprim–Sulfamethoxazole (Cotrimoxazole) |doi=10.1201/9781498747967 |chapter-url=https://www.taylorfrancis.com/chapters/edit/10.1201/9781498747967-92/trimethoprim-trimethoprim%E2%80%93sulfamethoxazole-cotrimoxazole-jason-trubiano-lindsay-grayson}}</ref><ref>{{Cite journal |vauthors=Brumfitt W, Hamilton-Miller JM |date=December 1993 |title=Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines |journal=Journal of Chemotherapy |volume=5 |issue=6 |pages=465–469 |doi=10.1080/1120009X.1993.11741097 |pmid=8195839}}</ref>
			{| class = wikitable
			|+ Pharmacokinetics of co-trimoxazole<ref name="MSR" /><ref name="TGA" />
			! Component !! T<sub>max</sub> (h) !! ] (L) !! Protein binding !! t<sub>1/2</sub> (h) ||Excretion
			|-
			| ] || 1-4 || 20 || 66% || 8-10 || Renal
			|-
			| ] || 1-4 || 130 || 42-45% || 10 || Renal
			|}
			== Society and culture ==
			=== Legal status ===
			{| class="wikitable"
			|+ <big>Indications for co-trimoxazole</big>
			! scope="col" | Indication
			! scope="col" | {{flagicon|USA}}<br />]-labelled indication?
			! scope="col" | {{flagicon|AUS}}<br />]-labelled indication?
			! scope="col" | {{flagicon|GBR}}<br />]-labelled indication?
			! scope="col" style="text-align: left;" | Literature support
			|-
			| Acute infective exacerbation of ] || {{Yes}} || {{No}} || {{No}} || Clinical trials are lacking.
			|-
			| Prophylaxis in ]-infected individuals || {{No}} || {{No}} || {{No}} || Effective in one ]n study on ], ], ] count, and ] in HIV infection.<ref>{{Cite journal |vauthors=Mermin J, Lule J, Ekwaru JP, Malamba S, Downing R, Ransom R, Kaharuza F, Culver D, Kizito F, Bunnell R, Kigozi A, Nakanjako D, Wafula W, Quick R |date=October 2004 |title=Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda |url=https://zenodo.org/record/1259795 |url-status=live |journal=Lancet |volume=364 |issue=9443 |pages=1428–1434 |doi=10.1016/S0140-6736(04)17225-5 |pmid=15488218 |s2cid=23402992 |archive-url=https://web.archive.org/web/20210118194652/https://zenodo.org/record/1259795 |archive-date=18 January 2021 |access-date=12 September 2020}}</ref>
			|-
			| ] || {{Yes|<small>Pediatric population only</small>}} || {{No}} || {{Yes}} || Clinical trials have confirmed its efficacy in chronic active<ref>{{Cite journal |vauthors=van der Veen EL, Rovers MM, Albers FW, Sanders EA, Schilder AG |date=May 2007 |title=Effectiveness of trimethoprim/sulfamethoxazole for children with chronic active otitis media: a randomized, placebo-controlled trial |journal=Pediatrics |volume=119 |issue=5 |pages=897–904 |doi=10.1542/peds.2006-2787 |pmid=17473089 |s2cid=23835227 |hdl-access=free |hdl=1874/25986}}</ref> and acute otitis media.<ref>{{Cite journal |vauthors=Leiberman A, Leibovitz E, Piglansky L, Raiz S, Press J, Yagupsky P, Dagan R |date=March 2001 |title=Bacteriologic and clinical efficacy of trimethoprim-sulfamethoxazole for treatment of acute otitis media |journal=The Pediatric Infectious Disease Journal |volume=20 |issue=3 |pages=260–264 |doi=10.1097/00006454-200103000-00009 |pmid=11303827 |s2cid=45262990}}</ref>
			|-
			| ], treatment & prophylaxis || {{Yes}} || {{No}} || {{No}} || Clinical trials have confirmed its efficacy as a treatment for travellers' diarrhea.<ref>{{Cite journal |vauthors=Ericsson CD, Johnson PC, Dupont HL, Morgan DR, Bitsura JA, de la Cabada FJ |date=February 1987 |title=Ciprofloxacin or trimethoprim-sulfamethoxazole as initial therapy for travelers' diarrhea. A placebo-controlled, randomized trial |journal=Annals of Internal Medicine |volume=106 |issue=2 |pages=216–220 |doi=10.7326/0003-4819-106-2-216 |pmid=3541724}}</ref><ref>{{Cite journal |vauthors=Ericsson CD, DuPont HL, Mathewson JJ, West MS, Johnson PC, Bitsura JA |date=January 1990 |title=Treatment of traveler's diarrhea with sulfamethoxazole and trimethoprim and loperamide |journal=JAMA |volume=263 |issue=2 |pages=257–261 |doi=10.1001/jama.1990.03440020091039 |pmid=2403603}}</ref><ref>{{Cite journal |vauthors=Rendi-Wagner P, Kollaritsch H |date=March 2002 |title=Drug prophylaxis for travelers' diarrhea |journal=Clinical Infectious Diseases |volume=34 |issue=5 |pages=628–633 |doi=10.1086/338640 |pmid=11803509 |doi-access=free |title-link=doi}}</ref>
			|-
			| ] || {{Yes}} || {{No}} || {{Yes}} || Clinical trials have confirmed its efficacy in this indication.<ref name="Drugs">{{Cite journal |vauthors=Wormser GP, Keusch GT, Heel RC |date=December 1982 |title=Co-trimoxazole (trimethoprim-sulfamethoxazole): an updated review of its antibacterial activity and clinical efficacy |journal=Drugs |volume=24 |issue=6 |pages=459–518 |doi=10.2165/00003495-198224060-00002 |pmid=6759092 |s2cid=209121818}}</ref>
			|-
			| colspan="5" align="center" | '''<big>Bacterial infections</big>'''
			|-
			| ] || {{No}} || {{No}} || {{No}} || At least one clinical trial supports its use in this indication.<ref>{{Cite journal |vauthors=Nordin K, Hallander H, Fredriksson T, Rylander C |year=1978 |title=A clinical and bacteriological evaluation of the effect of sulphamethoxazole-trimethoprim in acne vulgaris, resistant to prior therapy with tetracyclines |journal=Dermatologica |volume=157 |issue=4 |pages=245–253 |doi=10.1159/000250840 |pmid=150980}}</ref>
			|-
			| ] || {{No}} || {{Yes}} || {{No}} || Well-designed clinical trials are lacking.
			|-
			| ] || {{No}} || {{Yes}} || {{No}} || Clinical trials have confirmed its efficacy, with or without adjunctive ]; although, co-trimoxazole alone seems preferable.<ref>{{Cite journal |vauthors=Chetchotisakd P, Chaowagul W, Mootsikapun P, Budhsarawong D, Thinkamrop B |date=January 2001 |title=Maintenance therapy of melioidosis with ciprofloxacin plus azithromycin compared with cotrimoxazole plus doxycycline |journal=The American Journal of Tropical Medicine and Hygiene |volume=64 |issue=1–2 |pages=24–27 |doi=10.4269/ajtmh.2001.64.24 |pmid=11425157}}</ref><ref>{{Cite journal |vauthors=Chusri S, Hortiwakul T, Charoenmak B, Silpapojakul K |date=November 2012 |title=Outcomes of patients with melioidosis treated with cotrimoxazole alone for eradication therapy |journal=The American Journal of Tropical Medicine and Hygiene |volume=87 |issue=5 |pages=927–932 |doi=10.4269/ajtmh.2012.12-0136 |pmc=3516270 |pmid=23033403}}</ref><ref>{{Cite journal |vauthors=Chetchotisakd P, Chierakul W, Chaowagul W, Anunnatsiri S, Phimda K, Mootsikapun P, Chaisuksant S, Pilaikul J, Thinkhamrop B, Phiphitaporn S, Susaengrat W, Toondee C, Wongrattanacheewin S, Wuthiekanun V, Chantratita N, Thaipadungpanit J, Day NP, Limmathurotsakul D, Peacock SJ |date=March 2014 |title=Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial |journal=Lancet |volume=383 |issue=9919 |pages=807–814 |doi=10.1016/S0140-6736(13)61951-0 |pmc=3939931 |pmid=24284287}}</ref>
			|-
			| ] (whooping cough) || {{No}} || {{No}} || {{No}} || One ] supports its efficacy in preventing the spread of pertussis.<ref>{{Cite journal |vauthors=Altunaiji S, Kukuruzovic R, Curtis N, Massie J |date=July 2007 |title=Antibiotics for whooping cough (pertussis) |journal=] |volume=2013 |issue=3 |pages=CD004404 |doi=10.1002/14651858.CD004404.pub3 |pmc=11322855 |pmid=17636756}}</ref>
			|-
			| ] || {{Yes}} || {{Yes}} || {{No}} || Generally accepted treatment for shigellosis.<ref>{{Cite web |date=25 June 2012 |title=''Shigella'' Infection Medication |url=http://emedicine.medscape.com/article/968773-medication#showall |url-status=live |archive-url=https://web.archive.org/web/20140108135323/http://emedicine.medscape.com/article/968773-medication#showall |archive-date=8 January 2014 |access-date=8 January 2014 |website=Medscape Reference |publisher=WebMD |vauthors=Sureshbabu J, Venugopalan P, Abuhammour W |veditors=Fennelly G, Windle ML, Lutwick LI, Tolan Jr RW, Steele RW}}</ref> A Cochrane review found that while it is an effective treatment for shigellosis it also produces more significant adverse effects than other antibiotic drugs.<ref>{{Cite journal |vauthors=Christopher PR, David KV, John SM, Sankarapandian V |date=August 2010 |title=Antibiotic therapy for Shigella dysentery |journal=] |volume=2010 |issue=8 |pages=CD006784 |doi=10.1002/14651858.CD006784.pub4 |pmc=6532574 |pmid=20687081}}</ref>
			|-
			| '']'' infections || {{No}} || {{No}} || {{No}} || ''In vitro'' and ''in vivo'' activity against both non-resistant and ] (MRSA) infections.<ref>{{Cite journal |vauthors=Grim SA, Rapp RP, Martin CA, Evans ME |date=February 2005 |title=Trimethoprim-sulfamethoxazole as a viable treatment option for infections caused by methicillin-resistant Staphylococcus aureus |journal=Pharmacotherapy |volume=25 |issue=2 |pages=253–264 |doi=10.1592/phco.25.2.253.56956 |pmid=15767239 |s2cid=31546680}}</ref><ref>{{Cite journal |vauthors=Cenizal MJ, Skiest D, Luber S, Bedimo R, Davis P, Fox P, Delaney K, Hardy RD |date=July 2007 |title=Prospective randomized trial of empiric therapy with trimethoprim-sulfamethoxazole or doxycycline for outpatient skin and soft tissue infections in an area of high prevalence of methicillin-resistant Staphylococcus aureus |journal=Antimicrobial Agents and Chemotherapy |volume=51 |issue=7 |pages=2628–2630 |doi=10.1128/AAC.00206-07 |pmc=1913240 |pmid=17502411}}</ref><ref>{{Cite journal |vauthors=LaPlante KL, Leonard SN, Andes DR, Craig WA, Rybak MJ |date=June 2008 |title=Activities of clindamycin, daptomycin, doxycycline, linezolid, trimethoprim-sulfamethoxazole, and vancomycin against community-associated methicillin-resistant Staphylococcus aureus with inducible clindamycin resistance in murine thigh infection and in vitro pharmacodynamic models |journal=Antimicrobial Agents and Chemotherapy |volume=52 |issue=6 |pages=2156–2162 |doi=10.1128/AAC.01046-07 |pmc=2415789 |pmid=18411321}}</ref><ref>{{Cite journal |vauthors=Pappas G, Athanasoulia AP, Matthaiou DK, Falagas ME |date=April 2009 |title=Trimethoprim-sulfamethoxazole for methicillin-resistant Staphylococcus aureus: a forgotten alternative? |journal=Journal of Chemotherapy |volume=21 |issue=2 |pages=115–126 |doi=10.1179/joc.2009.21.2.115 |pmid=19423463 |s2cid=8425281}}</ref><ref>{{Cite journal |vauthors=Goldberg E, Paul M, Talker O, Samra Z, Raskin M, Hazzan R, Leibovici L, Bishara J |date=August 2010 |title=Co-trimoxazole versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteraemia: a retrospective cohort study |journal=The Journal of Antimicrobial Chemotherapy |volume=65 |issue=8 |pages=1779–1783 |doi=10.1093/jac/dkq179 |pmid=20507860 |doi-access=free |title-link=doi}}</ref><ref>{{Cite journal |vauthors=Cadena J, Nair S, Henao-Martinez AF, Jorgensen JH, Patterson JE, Sreeramoju PV |date=December 2011 |title=Dose of trimethoprim-sulfamethoxazole to treat skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus |journal=Antimicrobial Agents and Chemotherapy |volume=55 |issue=12 |pages=5430–5432 |doi=10.1128/AAC.00706-11 |pmc=3232808 |pmid=21930870}}</ref><ref>{{Cite journal |vauthors=Avery LM, Steed ME, Woodruff AE, Hasan M, Rybak MJ |date=November 2012 |title=Daptomycin-nonsusceptible vancomycin-intermediate staphylococcus aureus vertebral osteomyelitis cases complicated by bacteremia treated with high-dose daptomycin and trimethoprim-sulfamethoxazole |journal=Antimicrobial Agents and Chemotherapy |volume=56 |issue=11 |pages=5990–5993 |doi=10.1128/AAC.01046-12 |pmc=3486608 |pmid=22869580}}</ref>
			|-
			| ] || {{No}} || {{No}} || {{No}} || ''In vitro'' and ''in vivo'' activity against both nonresistant and MDR strains of TB.<ref>{{Cite journal |vauthors=Forgacs P, Wengenack NL, Hall L, Zimmerman SK, Silverman ML, Roberts GD |date=November 2009 |title=Tuberculosis and trimethoprim-sulfamethoxazole |journal=Antimicrobial Agents and Chemotherapy |volume=53 |issue=11 |pages=4789–4793 |doi=10.1128/AAC.01658-08 |pmc=2772331 |pmid=19564358}}</ref><ref>{{Cite journal |vauthors=Vilchèze C, Jacobs WR |date=October 2012 |title=The combination of sulfamethoxazole, trimethoprim, and isoniazid or rifampin is bactericidal and prevents the emergence of drug resistance in Mycobacterium tuberculosis |journal=Antimicrobial Agents and Chemotherapy |volume=56 |issue=10 |pages=5142–5148 |doi=10.1128/AAC.00832-12 |pmc=3457372 |pmid=22825115}}</ref><ref>{{Cite journal |vauthors=Alsaad N, van Altena R, Pranger AD, van Soolingen D, de Lange WC, van der Werf TS, Kosterink JG, Alffenaar JW |date=August 2013 |title=Evaluation of co-trimoxazole in the treatment of multidrug-resistant tuberculosis |journal=The European Respiratory Journal |volume=42 |issue=2 |pages=504–512 |doi=10.1183/09031936.00114812 |pmid=23100498 |doi-access=free |title-link=doi}}</ref>
			|-
			| ] || {{No}} || {{No}} || {{No}} || Co-trimoxazole is the recommended standard treatment for whipple's disease in some treatment protocols.<ref>{{Cite journal |vauthors=Fenollar F, Raoult D |date=January 2001 |title=Whipple's disease |journal=Clinical and Diagnostic Laboratory Immunology |volume=8 |issue=1 |pages=1–8 |doi=10.1128/CDLI.8.1.1-8.2001 |pmc=96003 |pmid=11139188}}</ref><ref>{{Cite journal |vauthors=Ojeda E, Cosme A, Lapaza J, Torrado J, Arruabarrena I, Alzate L |date=February 2010 |title=Whipple's disease in Spain: a clinical review of 91 patients diagnosed between 1947 and 2001 |journal=Revista Espanola de Enfermedades Digestivas |volume=102 |issue=2 |pages=108–123 |doi=10.4321/s1130-01082010000200006 |pmid=20361847 |doi-access=free |title-link=doi}}</ref><ref>{{Cite journal |vauthors=Puéchal X |date=November 2013 |title=Whipple's disease |journal=Postgraduate Medical Journal |volume=89 |issue=1057 |pages=659–665 |doi=10.1136/postgradmedj-2012-202684rep |pmid=24129033 |s2cid=24695700}}</ref>
			|-
			| colspan="5" align="center" | '''<big>Fungal and protozoal infections</big>'''
			|-
			| ] || {{No}} || {{No}} || {{No}} || Clinical trials have confirmed its use in this indication.<ref name="pmid18257775">{{Cite journal |vauthors=Lagrange-Xélot M, Porcher R, Sarfati C, de Castro N, Carel O, Magnier JD, Delcey V, Molina JM |date=February 2008 |title=Isosporiasis in patients with HIV infection in the highly active antiretroviral therapy era in France |journal=HIV Medicine |volume=9 |issue=2 |pages=126–130 |doi=10.1111/j.1468-1293.2007.00530.x |pmid=18257775 |s2cid=26120155 |doi-access=free |title-link=doi}}</ref>
			|-
			| ] || {{No}} || {{No}} || {{No}} || Clinical trials have confirmed its efficacy in both the treatment and prevention of malaria.<ref>{{Cite journal |vauthors=Manyando C, Njunju EM, D'Alessandro U, Van Geertruyden JP |year=2013 |title=Safety and efficacy of co-trimoxazole for treatment and prevention of Plasmodium falciparum malaria: a systematic review |journal=PLOS ONE |volume=8 |issue=2 |pages=e56916 |bibcode=2013PLoSO...856916M |doi=10.1371/journal.pone.0056916 |pmc=3579948 |pmid=23451110 |doi-access=free |title-link=doi}}</ref>
			|-
			| ] || {{Yes}} || {{Yes}} || {{Yes}} || Its use as a prophylactic treatment is supported by one clinical trial involving children with ].<ref>{{Cite journal |vauthors=Agrawal AK, Chang PP, Feusner J |date=January 2011 |title=Twice weekly Pneumocystis jiroveci pneumonia prophylaxis with trimethoprim-sulfamethoxazole in pediatric patients with acute lymphoblastic leukemia |journal=Journal of Pediatric Hematology/Oncology |volume=33 |issue=1 |pages=e1–e4 |doi=10.1097/MPH.0b013e3181fd6fca |pmid=21102354 |s2cid=42371307}}</ref> Other than this and one other clinical trial into its efficacy as a treatment for ''pneumocystis'' pneumonia,<ref>{{Cite journal |vauthors=Safrin S, Finkelstein DM, Feinberg J, Frame P, Simpson G, Wu A, Cheung T, Soeiro R, Hojczyk P, Black JR |date=May 1996 |title=Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 Study Group |journal=Annals of Internal Medicine |volume=124 |issue=9 |pages=792–802 |doi=10.7326/0003-4819-124-9-199605010-00003 |pmid=8610948 |s2cid=40999772}}</ref> data on its use in both the treatment and prevention of ''pneumocystis'' pneumonia is significantly lacking.
			|-
			| ] || {{Yes}} || {{Yes|<small>Prevention only</small>}} || {{Yes}} || Clinical trials have confirmed its prophylactic and therapeutic utility in cases of toxoplasmosis.<ref>{{Cite journal |vauthors=Canessa A, Del Bono V, De Leo P, Piersantelli N, Terragna A |date=February 1992 |title=Cotrimoxazole therapy of Toxoplasma gondii encephalitis in AIDS patients |journal=European Journal of Clinical Microbiology & Infectious Diseases |volume=11 |issue=2 |pages=125–130 |doi=10.1007/BF01967063 |pmid=1396726 |s2cid=13621055}}</ref><ref>{{Cite journal |vauthors=Torre D, Casari S, Speranza F, Donisi A, Gregis G, Poggio A, Ranieri S, Orani A, Angarano G, Chiodo F, Fiori G, Carosi G |date=June 1998 |title=Randomized trial of trimethoprim-sulfamethoxazole versus pyrimethamine-sulfadiazine for therapy of toxoplasmic encephalitis in patients with AIDS. Italian Collaborative Study Group |journal=Antimicrobial Agents and Chemotherapy |volume=42 |issue=6 |pages=1346–1349 |doi=10.1128/AAC.42.6.1346 |pmc=105601 |pmid=9624473}}</ref><ref>{{Cite journal |vauthors=Muñoz P, Arencibia J, Rodríguez C, Rivera M, Palomo J, Yañez J, Bouza E |date=April 2003 |title=Trimethoprim-sulfamethoxazole as toxoplasmosis prophylaxis for heart transplant recipients |journal=Clinical Infectious Diseases |volume=36 |issue=7 |pages=932–3; author reply 933 |doi=10.1086/368209 |pmid=12652396 |doi-access=free |title-link=doi}}</ref><ref>{{Cite journal |vauthors=Béraud G, Pierre-François S, Foltzer A, Abel S, Liautaud B, Smadja D, Cabié A |date=April 2009 |title=Cotrimoxazole for treatment of cerebral toxoplasmosis: an observational cohort study during 1994–2006 |journal=The American Journal of Tropical Medicine and Hygiene |volume=80 |issue=4 |pages=583–587 |doi=10.4269/ajtmh.2009.80.583 |pmid=19346380 |s2cid=22240685 |doi-access=free}}</ref><ref>{{Cite journal |vauthors=Alavi SM, Alavi L |date=September 2010 |title=Treatment of toxoplasmic lymphadenitis with co-trimoxazole: double-blind, randomized clinical trial |journal=International Journal of Infectious Diseases |volume=14 |issue=Supplement 3 |pages=e67–e69 |doi=10.1016/j.ijid.2009.11.015 |pmid=20194044 |doi-access=free |title-link=doi}}</ref><ref>{{Cite journal |vauthors=Patil HV, Patil VC, Rajmane V, Raje V |date=January 2011 |title=Successful treatment of cerebral toxoplasmosis with cotrimoxazole |journal=Indian Journal of Sexually Transmitted Diseases and AIDS |volume=32 |issue=1 |pages=44–46 |doi=10.4103/0253-7184.81255 |pmc=3139289 |pmid=21799577 |doi-access=free}}</ref>
			|-
			|}
			=== Brand names ===
			Trimethoprim/sulfamethoxazole may be abbreviated as SXT, SMZ-TMP, TMP-SMX, TMP-SMZ, or TMP-sulfa.{{citation needed|date=December 2021}} The generic ] (BAN) Co-trimoxazole is used for trimethoprim/sulfamethoxazole manufactured and sold by many different companies.<ref>{{Cite web |title=Co-trimoxazole Medicinal forms |url=https://bnf.nice.org.uk/drugs/co-trimoxazole/medicinal-forms/#oral-tablet |access-date=4 June 2024 |publisher=NICE}}</ref>
			The following list of brand names is incomplete:
			{{div col|colwidth=22em}}
			* Bactrim, Bactrimel (manufactured by ] 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 (])
			* Diseptyl (Israel)
			* Graprima Forte Kaplet (manufactured by PT Graha Farma and distributed in Indonesia)
			* Infectrin, Bactrim (Brazil)
			* Novo-Trimel<ref name="Novo-Trimel">{{Cite web |title=Novo-Trimel Advanced Patient Information – Drugs.com |url=https://www.drugs.com/cons/novo-trimel.html |url-status=live |archive-url=https://web.archive.org/web/20180201192950/https://www.drugs.com/cons/novo-trimel.html |archive-date=1 February 2018 |access-date=1 February 2018 |website=Drugs.com}}</ref>
			* Primadex (manufactured by Dexa Medica and distributed in Indonesia)
			* Primotren (] in ] and other countries)
			* Resprim
			* Sanprima (manufactured by PT Sanbe Farma and distributed in Indonesia)
			* Septra (] and formerly ])
			* Septram (Panama)
			* Septran (GlaxoSmithKline)<ref name="GSK2017">{{Cite web |date=13 August 2017 |title=Septran/Sepman Double Strength – Co-Trimoxazole Oral Formulations |url=http://india-pharma.gsk.com/media/701285/septran-and-sepmax.pdf |url-status=live |archive-url=https://web.archive.org/web/20180601211744/http://india-pharma.gsk.com/media/701285/septran-and-sepmax.pdf |archive-date=1 June 2018 |access-date=1 June 2018 |publisher=GlaxoSmithKline}}</ref>
			* Septrin (Spain)<ref>{{Cite web |title=SEPTRIN FORTE Comp. 800/160 mg – Datos generales |url=http://www.vademecum.es/medicamento-septrin+forte_3626 |url-status=live |archive-url=https://web.archive.org/web/20150616233203/http://www.vademecum.es/medicamento-septrin+forte_3626 |archive-date=16 June 2015 |access-date=17 August 2015}}</ref>
			* Sulfatrim
			* Teva-Trimel
			* Trisul
			* Vactrim (manufactured and distributed in Laos)
			{{div col end}}
			=== Economics ===
			Trimethoprim/sulfamethoxazole is relatively inexpensive as of 2019.<ref name="Brown2019">{{Cite book |url=https://books.google.com/books?id=_nTADwAAQBAJ&dq=Cefalexin+relatively+inexpensive&pg=PA1173 |title=Lewis's Medical-Surgical Nursing EBook: Assessment and Management of Clinical Problems |vauthors=Brown D, Edwards H, Buckley T, Aitken RL |date=2019 |publisher=Elsevier Health Sciences |isbn=978-0-7295-8708-2 |page=1173 |access-date=30 March 2020 |archive-url=https://web.archive.org/web/20210829095029/https://www.google.com/books/edition/Lewis_s_Medical_Surgical_Nursing_EBook/_nTADwAAQBAJ?hl=en&gbpv=1&dq=Cefalexin+relatively+inexpensive&pg=PA1173 |archive-date=29 August 2021 |url-status=live}}</ref>
			== References ==
			{{Reflist}}
	{{Nucleic acid inhibitors}}		{{Nucleic acid inhibitors}}
	{{Antiprotozoal agent}}		{{Antiprotozoal agent}}
			{{Portal bar|Medicine}}
			{{Authority control}}
	{{DEFAULTSORT:Co-Trimoxazole}}		{{DEFAULTSORT:Trimethoprim Sulfamethoxazole}}
			]
	]		]
			]
			]
			]
			]
	]		]
			]
	]
	]
	]
	]
	]
	]
	]
	]
	]
	]