Sulfadoxine/pyrimethamine

It is approved in the United States as a treatment and preventive measure against malaria. The combination is considered to be more effective in treating malaria caused by Plasmodium falciparum than that caused by P. vivax, for which chloroquine is considered more effective, though in the absence of a species-specific diagnosis, the sulfadoxine-pyrimethamine combination may be indicated.[http://jama.ama-assn.org/cgi/content/abstract/297/20/2201 JAMA -Abstract: Sulfadoxine-Pyrimethamine, Chlorproguanil-Dapsone, or Chloroquine for the Treatment of Plasmodium vivax Malaria in Afghanistan and Pakistan: A Randomized Controlled Trial, May 23/30, 2007, Leslie et al. 297 (20): 2201] {{webarchive|url=https://web.archive.org/web/20080709084005/http://jama.ama-assn.org/cgi/content/abstract/297/20/2201 |date=9 July 2008 }}. Due to side effects, however, it is no longer recommended as a routine preventive,{{cite web | title = Medical Treatment - Sulphadoxine and Pyrimethamine | url = http://www.malaria-ipca.com/sulphadoxine_pyrimethamine.html |access-date=31 August 2011 |archive-date=28 December 2007 |archive-url=https://web.archive.org/web/20071228220926/http://www.malaria-ipca.com/sulphadoxine_pyrimethamine.html |url-status=dead }} but only to treat serious malaria infections or to prevent them in areas where other drugs may not work.[http://www.mayoclinic.com/health/drug-information/DR600357 Pyrimethamine and Sulfadoxine (Oral Route) - MayoClinic.com] {{webarchive|url=https://web.archive.org/web/20110612153023/http://www.mayoclinic.com/health/drug-information/DR600357 |date=12 June 2011 }}. However, it is recommended by the World Health Organization (WHO) for seasonal preventative use in children when combined with amodiaquine.{{cite book |vauthors=((World Health Organization)) |title=Seasonal malaria chemoprevention with sulfadoxine–pyrimethamine plus amodiaquine in children: a field guide |location=Geneva |publisher=World Health Organization (WHO) |date=August 2013 |isbn=978-92-4-150473-7 |hdl=10665/85726 |hdl-access=free}}

It has also be used as a treatment and prophylactic measure for toxoplasmosis and Pneumocystis jiroveci pneumonia.{{cite journal | vauthors = Bath PM, Lillicrap DA, Winter M | title = Fansidar--a treatment for AIDS-related pneumocystis? | journal = Postgraduate Medical Journal | volume = 63 | issue = 740 | pages = 509–510 | date = June 1987 | pmid = 3501583 | pmc = 2428336 | doi = 10.1136/pgmj.63.740.509-a }}{{cite journal | vauthors = Foot AB, Garin YJ, Ribaud P, Devergie A, Derouin F, Gluckman E | title = Prophylaxis of toxoplasmosis infection with pyrimethamine/sulfadoxine (Fansidar) in bone marrow transplant recipients | journal = Bone Marrow Transplantation | volume = 14 | issue = 2 | pages = 241–245 | date = August 1994 | pmid = 7994239 }}{{cite journal | vauthors = Bessesen MT, Miller LA, Cohn DL, Bartlett S, Ellison RT | title = Administration of pyrimethamine/sulfadoxine for prevention of Pneumocystis carinii pneumonia in patients with AIDS | journal = Clinical Infectious Diseases | volume = 20 | issue = 3 | pages = 730–731 | date = March 1995 | pmid = 7756514 | doi = 10.1093/clinids/20.3.730 }}{{cite journal | vauthors = Michalová K, Ríhová E, Havlíková M | title = [Fansidar in the treatment of toxoplasmosis] | language = cs | journal = Ceska a Slovenska Oftalmologie | volume = 52 | issue = 3 | pages = 173–178 | date = July 1996 | pmid = 8768475 }}{{cite journal | vauthors = Schürmann D, Bergmann F, Albrecht H, Padberg J, Grünewald T, Behnsch M, Grobusch M, Vallée M, Wünsche T, Ruf B, Suttorp N | title = Twice-weekly pyrimethamine-sulfadoxine effectively prevents Pneumocystis carinii pneumonia relapse and toxoplasmic encephalitis in patients with AIDS | journal = The Journal of Infection | volume = 42 | issue = 1 | pages = 8–15 | date = January 2001 | pmid = 11243747 | doi = 10.1053/jinf.2000.0772 }}

Adverse effects by incidence include:{{cite web|title=Pyrimethamine, Sulfadoxine and Pyrimethamine Monograph for Professionals|work=Drugs.com|publisher=American Society of Health-System Pharmacists|access-date=9 January 2014|url=https://www.drugs.com/monograph/pyrimethamine-sulfadoxine-and-pyrimethamine.html|url-status=live|archive-url=https://web.archive.org/web/20140109145912/http://www.drugs.com/monograph/pyrimethamine-sulfadoxine-and-pyrimethamine.html|archive-date=9 January 2014}}{{cite web|title=Fansidar, Pyrimethamine-sulfadoxine (pyrimethamine/sulfadoxine) dosing, indications, interactions, adverse effects, and more|work=Medscape Reference|publisher=WebMD|access-date=9 January 2014|url=http://reference.medscape.com/drug/fansidar-pyrimethamine-sulfadoxine-342694#showall|url-status=live|archive-url=https://web.archive.org/web/20140109135919/http://reference.medscape.com/drug/fansidar-pyrimethamine-sulfadoxine-342694#showall|archive-date=9 January 2014}}{{cite book | isbn = 978-0-85711-084-8 | title = British National Formulary (BNF) | last1 = Joint Formulary Committee | year = 2013 | publisher = Pharmaceutical Press | location = London, UK | edition = 65 | page = [https://archive.org/details/bnf65britishnati0000unse/page/429 429] | url = https://archive.org/details/bnf65britishnati0000unse/page/429 }}{{cite web|title=Fansidar (sulfadoxine and pyrimethamine)|work=medicines.org.au|publisher=Roche Products Pty Limited|date=17 April 2008|access-date=9 January 2014|url=http://www.medicines.org.au/files/ropfansi.pdf|url-status=live|archive-url=https://web.archive.org/web/20140109142735/http://www.medicines.org.au/files/ropfansi.pdf|archive-date=9 January 2014}}

Common (>1% frequency):

• Hypersensitivity reactions (e.g. itchiness, contact dermatitis, and hives)
• Myelosuppression
• Gastrointestinal effects (e.g. nausea, vomiting, and diarrhoea)
• Headache

Rare (<1% frequency):

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• Stevens–Johnson syndrome
• Toxic epidermal necrolysis
• Agranulocytosis
• Aplastic anaemia
• Disorder of haematopoietic structure
• Drug-induced eosinophilia
• Thrombocytopaenia
• Liver necrosis
• Hepatitis
• Jaundice
• Hepatomegaly
• Nephrotoxicity

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Unknown frequency:

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• Weight loss
• Abdominal cramps
• Hair loss
• Photosensitivity
• Fatigue
• Fever
• Polyneuritis
• Atrophic glossitis
• Gastritis

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• Abnormal liver function test results (e.g. elevated serum ALT, AST, alkaline phosphatase, and bilirubin concentrations)

Use of this drug is contraindicated in:

• Megaloblastic anaemia caused by folate deficiency
• Hypersensitivity to pyrimethamine, sulfonamides, or any ingredient in the formulation
• Repeated prophylactic (prolonged) use in patients with kidney or liver failure or blood dyscrasias
• Infants <2 months of age
• Prophylaxis in pregnancy at term
• Prophylaxis in nursing women
• Acute porphyria

Sulfadoxine is a sulfonamide antibiotic that competes with p-aminobenzoic acid in the biosynthesis of folate. Pyrimethamine serves as a selective inhibitor of protozoal dihydrofolate reductase, hence preventing the synthesis of tetrahydrofolate — the active form of folate. A great degree of synergy occurs between the two drugs due to their inhibition of two different steps in the biosynthesis of tetrahydrofolate.

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