Sulfadoxine is a sulfonamide
Sulfonamides are synthetic drugs with low potency against a wide range of parasitic organisms including Plasmodia, T. gondii and P. carinii.
Sulphonamides act through inhibition of dihydropteroate synthetase. Resistance arises through multiple mutations in this gene.
Sulfadoxine is available (combined with pyrimethamine) in both oral and intramuscular forms. It is rapidly and extensively absorbed from the gut. Sulfadoxine is about 94% bound to plasma proteins. T1/2 is around184 hours in healthy adults following oral dosing.
In the treatment of Plasmodium falciparum, sulfadoxine is always used in fixed-ratio combination with pyrimethamine. For adults, a single dose of sulfadoxine, 1.5 g, is given with pyrimethamine 75 mg. The drug is contraindicated in patients with severe renal insufficiency, marked liver parenchymal damage or blood dyscrasias.
The adverse effects of sulfonamides may be considered for the group as a whole. Differences in frequency and severity of reactions are largely a function of elimination rate: bizarre reactions to slowly eliminated drugs being more severe because drug exposure is longer. Most are of a ‘type B’ or bizarre type and many are thought to involve the immune system. They include fever, arthralgia, bone marrow adverse reactions including neutropaenia, agranulocytosis, and aplastic anaemia, rashes which range from the trivial to the life-threatening and methemoglobinaemia and haemolysis in patients with glucose-6-phosphate dehydrogenase deficiency. The commonest serious type A adverse reaction is crystalluria.
Sulfadoxine is a sulfonamide antimicrobial that, when administered during the last trimester of pregnancy, theoretically could compete with bilirubin for plasma proteins and exacerbate neonatal jaundice. It is unclear, however, whether this specific sulfa congener poses any risk to the newborn.
Sulfonamides generally are prone to adverse drug interactions by three principal mechanisms:
• Displacement from plasma protein binding
• Inhibition of biotransformation
• Additive pharmacodynamic response
The first two mechanisms, occurring together, explain the ‘toxic’ potentiation of several drugs with the following common characteristics:
• Cleared by biotransformation to a large degree
• Extensively bound to plasma proteins
• Narrow therapeutic range
Included in this list are: warfarin (and other coumarins), sulfonylureas and phenytoin
Fansidar™ (Roche) tablets containing pyrimethamine (25mg) and sulfadoxine (500mg).