Sulfadoxine/pyrimethamine

Sulfadoxine/pyrimethamine, sold under the brandname 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]

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
  • US: C (Risk not ruled out)
    Routes of
    administration    		by mouth
    ATC code
    Legal status
    Legal status
    • AU: S4 (Prescription only)
    • UK: POM (Prescription only)
    • US: ℞-only
      (verify)

    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 is unclear if use during pregnancy is safe for the baby.[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, the most effective and safe medicines needed in a health system.[5] The wholesale cost in the developing world is about US$0.08–0.36 per day.[6] It is not currently commercially available in the United States.[1]

    Medical uses

    Malaria

    It is approved by the United States' Food and Drug Administration for use as a treatment and preventive measure against malaria.[7] 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.[8] Due to side effects, however, it is no longer recommended as a routine preventive,[9] but only to treat serious malaria infections or to prevent them in areas where other drugs may not work.[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:[7][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:[7][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.[7] Pyrimethamine serves as a selective inhibitor of protozoal dihydrofolate reductase, hence preventing the synthesis of tetrahydrofolate — the active form of folate.[7] A great degree of synergy occurs between the two drugs due to their inhibition of two different steps in the biosynthesis of tetrahydrofolate.[7]

    Pharmacokinetics
    Pharmacokinetic parameterPyrimethamineSulfadoxine
    Half-life111 hours169 hours
    Cmax0.2 mg/l60 mg/L
    Tmax4 hours4 hours
    Protein bound87%90%
    ExcretionRenal (16-30%)Renal (30%)
    MetabolismHepaticHepatic

    See also

    References
    1. "Pyrimethamine/sulfadoxine: Indications, Side Effects, Warnings - Drugs.com". www.drugs.com. Archived from the original on 20 December 2016. Retrieved 11 December 2016.
    2. 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) (PDF). WHO. 2015. p. 435. ISBN 9789240694941. Archived (PDF) from the original on 20 December 2016. Retrieved 8 December 2016.
    3. WHO Model Formulary 2008 (PDF). World Health Organization. 2009. pp. 187, 198–1999. ISBN 9789241547659. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
    4. "Pyrimethamine / sulfadoxine (Fansidar) Use During Pregnancy". www.drugs.com. Archived from the original on 20 December 2016. Retrieved 11 December 2016.
    5. "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
    6. "Sulfadoxine + Pyrimethamine". International Drug Price Indicator Guide. Retrieved 8 December 2016.
    7. "Pyrimethamine, Sulfadoxine and Pyrimethamine Monograph for Professionals". Drugs.com. Archived from the original on 9 January 2014. Retrieved 9 January 2014.
    8. 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.
    9. Medical Treatment - Sulphadoxine and Pyrimethamine Archived 2007-12-28 at the Wayback Machine.
    10. Pyrimethamine and Sulfadoxine (Oral Route) - MayoClinic.com Archived 2011-06-12 at the Wayback Machine.
    11. "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 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.
    15. 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.
    16. 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.
    17. 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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