Sulfadoxine/pyrimethamine

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Sulfadoxine/pyrimethamine
Combination of
SulfadoxineSulfonamide
PyrimethamineAntiparasitic
Names
Pronunciationpeer-i-METH-a-meen/sul-fa-DOX-een[1]
Trade namesFansidar, Fanlar, others
Clinical data
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
Routes of
use
By mouth
Defined daily dosenot established[2]
External links
AHFS/Drugs.comConsumer Drug Information
Legal
License data
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
  (verify)

Sulfadoxine/pyrimethamine, sold under the brand name Fansidar, is a combination medication used to treat malaria.[1][3] It contains sulfadoxine (a sulfonamide) and pyrimethamine (an antiprotozoal).[4] For the treatment of malaria it is typically used along with other antimalarial medication such as artesunate.[4] In areas of Africa with moderate to high rates of malaria, three doses are recommended during the second and third trimester of pregnancy.[5]

Side effects include diarrhea, rash, itchiness, headache, and hair loss.[4][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.[4] 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.[6] The wholesale cost in the developing world is about US$0.08–0.36 per day.[7] 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.[8] 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.[9] Due to side effects, however, it is no longer recommended as a routine preventive,[10] but only to treat serious malaria infections or to prevent them in areas where other drugs may not work.[11] However, it is recommended by the World Health Organization (WHO) for seasonal preventative use in children when combined with amodiaquine.[12]

Other

It has also be used to treat and prevent toxoplasmosis and Pneumocystis jiroveci pneumonia.[13][14][15][16][17][18]

Dosage

The defined daily dose is not established.[2] For the prevention of malaria in regions were the disease is common, 1500 mg sulfadoxine / 75 mg pyrimethamine is recommended at the start of the second trimester followed by two more doses at least a month apart during pregnancy.[19]

Side effects

Side effects by include:[8][13][20][21]

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:[8][20]

  • 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

Pregnancy and breastfeeding

It should not be used in the first trimester of pregnancy due to the risk of neural tube defects.[19]

Pharmacology

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

Sulfadoxine is a sulfonamide antibiotic that competes with p-aminobenzoic acid in the biosynthesis of folate.[8] Pyrimethamine serves as a selective inhibitor of protozoal dihydrofolate reductase, hence preventing the synthesis of tetrahydrofolate — the active form of folate.[8] A great degree of synergy occurs between the two drugs due to their inhibition of two different steps in the biosynthesis of tetrahydrofolate.[8]

See also

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "Pyrimethamine/sulfadoxine: Indications, Side Effects, Warnings - Drugs.com". www.drugs.com. Archived from the original on 20 December 2016. Retrieved 11 December 2016.
  2. 2.0 2.1 "WHOCC - ATC/DDD Index". www.whocc.no. Retrieved 20 September 2020.
  3. 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.
  4. 4.0 4.1 4.2 4.3 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.
  5. "Intermittent preventive treatment in pregnancy (IPTp)". WHO. Retrieved 22 May 2020.
  6. 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.
  7. "Sulfadoxine + Pyrimethamine". International Drug Price Indicator Guide. Retrieved 8 December 2016.
  8. 8.0 8.1 8.2 8.3 8.4 8.5 "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.
  9. 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 2008-07-09 at the Wayback Machine.
  10. Medical Treatment - Sulphadoxine and Pyrimethamine Archived 2007-12-28 at the Wayback Machine.
  11. Pyrimethamine and Sulfadoxine (Oral Route) - MayoClinic.com Archived 2011-06-12 at the Wayback Machine.
  12. 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.
  13. 13.0 13.1 "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.
  14. 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.
  15. 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.
  16. Bessesen, MT; Miller, LA; Cohn, DL; Bartlett, S; Ellison, RT 3rd (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.
  17. Michalová, K; Ríhová, E; Havlíková, M (July 1996). "[Fansidar in the treatment of toxoplasmosis]". Cesk Slov Oftalmol. (in Czech). 52 (3): 173–178. PMID 8768475.CS1 maint: unrecognized language (link)
  18. Schürmann, D; Bergmann, F; Albrecht, H; Padberg, J; Grünewald, T; Behnsch, M; Grobusch, M; Vallée, M; Wünsche, T; Ruf, B; Suttorp, N (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.
  19. 19.0 19.1 "SULFADOXINE/PYRIMETHAMINE = SP oral - Essential drugs". medicalguidelines.msf.org. Retrieved 25 August 2020.
  20. 20.0 20.1 Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. p. 429. ISBN 978-0-85711-084-8.
  21. "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.

External links

Identifiers: