Sulfadoxine/pyrimethamine

Sulfadoxine/pyrimethamine
Combination of
SulfadoxineSulfonamide
PyrimethamineAntiparasitic
Clinical data
Pronunciationpeer-i-METH-a-meen/sul-fa-DOX-een[1]
Trade namesFansidar, Fanlar, others
AHFS/Drugs.comConsumer Drug Information
License data
Pregnancy
category
  • AU: C
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Identifiers
CAS Number
KEGG
  (verify)

Sulfadoxine/pyrimethamine, sold under the brand name Fansidar, is a combination medication used to treat malaria.[1][2] It contains sulfadoxine (a sulfonamide) and pyrimethamine (an antiprotozoal).[3] For the treatment of malaria it is typically used along with other antimalarial medication such as artesunate.[3] In areas of Africa with moderate to high rates of malaria, three doses are recommended during the second and third trimester of pregnancy.[4]

Side effects include diarrhea, rash, itchiness, headache, and hair loss.[3][1] Rarely a severe allergic reaction or rash such as toxic epidermal necrolysis, may occur.[1] It is not generally recommended in people with a sulfonamide allergy or significant liver or kidney disease.[3] It works by blocking malaria's ability to use folinic acid.[1]

Sulfadoxine/pyrimethamine was initially approved for medical use in the United States in 1981.[1] It is on the World Health Organization's List of Essential Medicines.[5] It is not commercially available in the United States.[1]

Medical uses

Malaria

It is approved in the United States as a treatment and preventive measure against malaria.[6] 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.[7] Due to side effects, however, it is no longer recommended as a routine preventive,[8] but only to treat serious malaria infections or to prevent them in areas where other drugs may not work.[9] However, it is recommended by the World Health Organization (WHO) for seasonal preventative use in children when combined with amodiaquine.[10]

Other

It has also be used as a treatment and prophylactic measure for toxoplasmosis and Pneumocystis jiroveci pneumonia.[11][12][13][14][15][16]

Adverse effects

Adverse effects by incidence include:[6][11][17][18]

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):

Unknown frequency:

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

Contraindications

Use of this drug is contraindicated in:[6][17]

  • 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

Pharmacology

Sulfadoxine is a sulfonamide antibiotic that competes with p-aminobenzoic acid in the biosynthesis of folate.[6] Pyrimethamine serves as a selective inhibitor of protozoal dihydrofolate reductase, hence preventing the synthesis of tetrahydrofolate — the active form of folate.[6] A great degree of synergy occurs between the two drugs due to their inhibition of two different steps in the biosynthesis of tetrahydrofolate.[6]

Pharmacokinetics
Pharmacokinetic parameter Pyrimethamine Sulfadoxine
Half-life 111 hours 169 hours
Cmax 0.2 mg/L 60 mg/L
Tmax 4 hours 4 hours
Protein bound 87% 90%
Excretion Renal (16-30%) Renal (30%)
Metabolism Hepatic Hepatic

References

  1. ^ a b c d e f g "Pyrimethamine/sulfadoxine: Indications, Side Effects, Warnings - Drugs.com". www.drugs.com. Archived from the original on 20 December 2016. Retrieved 11 December 2016.
  2. ^ World Health Organization (2015). The selection and use of essential medicines. Twentieth report of the WHO Expert Committee 2015 (including 19th WHO Model List of Essential Medicines and 5th WHO Model List of Essential Medicines for Children). Geneva: World Health Organization. hdl:10665/189763. ISBN 9789241209946. ISSN 0512-3054. WHO technical report series;994.
  3. ^ a b c d World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. pp. 187–91, 198–200. hdl:10665/44053. ISBN 9789241547659.
  4. ^ "Intermittent preventive treatment in pregnancy (IPTp)". WHO. Archived from the original on 5 March 2014. Retrieved 22 May 2020.
  5. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  6. ^ a b c d e f "Pyrimethamine, Sulfadoxine and Pyrimethamine Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 9 January 2014. Retrieved 9 January 2014.
  7. ^ 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 Archived 9 July 2008 at the Wayback Machine.
  8. ^ "Medical Treatment - Sulphadoxine and Pyrimethamine". Archived from the original on 28 December 2007. Retrieved 31 August 2011.
  9. ^ Pyrimethamine and Sulfadoxine (Oral Route) - MayoClinic.com Archived 12 June 2011 at the Wayback Machine.
  10. ^ World Health Organization (August 2013). Seasonal malaria chemoprevention with sulfadoxine–pyrimethamine plus amodiaquine in children: a field guide. Geneva: World Health Organization (WHO). hdl:10665/85726. ISBN 978-92-4-150473-7.
  11. ^ a b "Fansidar, Pyrimethamine-sulfadoxine (pyrimethamine/sulfadoxine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 9 January 2014. Retrieved 9 January 2014.
  12. ^ Bath PM, Lillicrap DA, Winter M (June 1987). "Fansidar--a treatment for AIDS-related pneumocystis?". Postgraduate Medical Journal. 63 (740): 509–510. doi:10.1136/pgmj.63.740.509-a. PMC 2428336. PMID 3501583.
  13. ^ Foot AB, Garin YJ, Ribaud P, Devergie A, Derouin F, Gluckman E (August 1994). "Prophylaxis of toxoplasmosis infection with pyrimethamine/sulfadoxine (Fansidar) in bone marrow transplant recipients". Bone Marrow Transplantation. 14 (2): 241–245. PMID 7994239.
  14. ^ Bessesen MT, Miller LA, Cohn DL, Bartlett S, Ellison RT (March 1995). "Administration of pyrimethamine/sulfadoxine for prevention of Pneumocystis carinii pneumonia in patients with AIDS". Clinical Infectious Diseases. 20 (3): 730–731. doi:10.1093/clinids/20.3.730. PMID 7756514.
  15. ^ Michalová K, Ríhová E, Havlíková M (July 1996). "[Fansidar in the treatment of toxoplasmosis]". Ceska a Slovenska Oftalmologie (in Czech). 52 (3): 173–178. PMID 8768475.
  16. ^ Schürmann D, Bergmann F, Albrecht H, Padberg J, Grünewald T, Behnsch M, et al. (January 2001). "Twice-weekly pyrimethamine-sulfadoxine effectively prevents Pneumocystis carinii pneumonia relapse and toxoplasmic encephalitis in patients with AIDS". The Journal of Infection. 42 (1): 8–15. doi:10.1053/jinf.2000.0772. PMID 11243747.
  17. ^ a b Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. p. 429. ISBN 978-0-85711-084-8.
  18. ^ "Fansidar (sulfadoxine and pyrimethamine)" (PDF). medicines.org.au. Roche Products Pty Limited. 17 April 2008. Archived (PDF) from the original on 9 January 2014. Retrieved 9 January 2014.

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