Antimalarial antifolate (sulfonamide + diaminopyrimidine)
Sulfadoxine + pyrimethamine is an antimalarial used mainly for intermittent preventive treatment of malaria in pregnancy and seasonal chemoprevention in children, in areas where the parasite remains sensitive. It is taken orally, usually as supervised single doses. Like all sulfonamide medicines, it can cause severe skin reactions.
Also known as: Fansidar
Two sulfonamide-containing drugs (Sulfadoxine + Sulfamethoxazole) — additive risk of severe hypersensitivity reactions (e.g. Stevens-Johnson syndrome) and bone marrow suppression.
Co-trimoxazole (sulfamethoxazole + trimethoprim) and sulfadoxine-pyrimethamine share sulfonamide components (sulfamethoxazole and sulfadoxine) and antifolate components (trimethoprim and pyrimethamine, both dihydrofolate reductase inhibitors); the combination adds up the risk of haematological adverse reactions (megaloblastic anaemia, neutropenia, thrombocytopenia from folate depletion), severe skin reactions and hypersensitivity, with no additional antimicrobial benefit. The WHO (Guidelines for malaria) does not recommend the concomitant use of two sulfonamide/antifolate combinations. Avoid the combination and choose an alternative regimen; if unavoidable, monitor the blood count and liver function.
Co-trimoxazole + sulfadoxine-pyrimethamine: combination of sulfonamides with antifolate — additive risk of haematological reactions and hypersensitivity. Avoid.
Sulfadoxine and Sulfamethoxazole share the sulfonamide group; both are also antifolates (with Pyrimethamine and Trimethoprim).
Skin (rash, blisters), blood count and renal function.
Extensive rash, blisters/skin detachment, fever, anaemia, jaundice.
Avoid the association; use an alternative antibiotic whenever possible.
WHO — WHO Guidelines for malaria: https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria ; DailyMed/FDA (NIH/NLM) — approved Co-trimoxazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=08500fcb-dbec-4ac2-91c3-189d27907ec0
Sulfadoxine (a sulfonamide) may enhance the effect of Warfarin — bleeding risk.
Sulphonamides, such as sulphadoxine, have been associated with increased warfarin effect through multiple mechanisms: CYP2C9 inhibition (metabolism of active S-warfarin), displacement of protein binding and, potentially, reduction of the gut flora producing vitamin K. Pyrimethamine contributes less, but the two are used together in malaria prophylaxis and treatment. The INR should be monitored at the start and end of treatment and the warfarin dose adjusted; watch for bleeding signs.
Sulfadoxine (a sulphonamide) can inhibit warfarin metabolism and displace the free fraction, raising the INR. Monitor the INR during and after the antimalarial.
Possible inhibition of Warfarin metabolism and/or protein-binding displacement.
INR and signs of bleeding.
Bleeding, bruising, dark stools.
Monitor the INR on starting/stopping and adjust the dose.
WHO — WHO Guidelines for malaria: https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria ; DailyMed/FDA (NIH/NLM) — approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057
Alcohol may worsen the gastrointestinal effects of sulfadoxine + pyrimethamine; limit intake.
Limit alcohol intake during treatment.
WHO — Malaria guidelines (sulfadoxine + pyrimethamine): https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria
Sulfadoxine + pyrimethamine can be taken with or without food; taking with food reduces gastrointestinal discomfort.
Take with food if gastric discomfort occurs.
WHO — Malaria guidelines (sulfadoxine + pyrimethamine): https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria
Sulfadoxine can cause haemolysis in patients with G6PD deficiency; use with caution and monitor for signs of haemolysis.
Use with caution in G6PD deficiency; monitor haemoglobin and signs of haemolysis.
WHO — Malaria guidelines (sulfadoxine + pyrimethamine): https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria
Sulfadoxine is a sulphonamide; it is contraindicated in patients with prior sulphonamide allergy (risk of severe reactions, including SJS/TEN).
Contraindicated in sulphonamide allergy; choose an alternative antimalarial.
WHO — Malaria guidelines (sulfadoxine + pyrimethamine): https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria
Sulfadoxine + pyrimethamine is used in pregnancy as intermittent preventive treatment of malaria (IPTp) from the 2nd trimester, with folic acid supplementation.
Use as IPTp in the 2nd and 3rd trimesters, with folic acid.
Excreted into breast milk in small amounts; compatible with breastfeeding under supervision.
No specific additional contraception.
WHO — Malaria guidelines (sulfadoxine + pyrimethamine): https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Synergistic combination of two antifolates: pyrimethamine inhibits the parasite dihydrofolate reductase and sulfadoxine (a sulfonamide) inhibits dihydropteroate synthase, blocking plasmodial folate synthesis at two points. This action is slow-acting, long-lasting blood schizonticidal, suitable for prevention but not for curative treatment of acute malaria.
Pyrimethamine antagonises parasite folic acid by inhibiting dihydrofolate reductase; sulfadoxine competitively inhibits dihydropteroate synthase. The sequential blockade of tetrahydrofolate synthesis is lethal to the dividing plasmodium.
Oral bioavailability over 90% for both drugs; peak plasma levels occur about 3 hours after dosing. Sulfadoxine has a volume of distribution of 0.14 L/kg and pyrimethamine of 2.3 L/kg (wide distribution; crosses the placenta and passes into milk).
Sulfadoxine is partially metabolised (N-acetylation and glucuronidation); pyrimethamine is extensively metabolised in the liver. Both are eliminated mainly by the kidneys, with long half-lives that sustain the prolonged preventive effect.
Long half-lives: about 200 hours (~8-9 days) for sulfadoxine and about 100 hours (~4 days) for pyrimethamine; they accumulate in patients with renal or hepatic failure.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
