Sulfadoxine and its drug use

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Introduction

Sulfadoxine (also spelled sulphadoxine) is an ultra-long-lasting sulfonamide used in combination with pyrimethamine to treat malaria. It is also used to prevent malaria but due to high levels of resistance, this use is becoming less common. It is also used, usually in combination with other drugs, to treat or prevent various infections in livestock.

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.

Dosage

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.

Adverse Effects

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.

Drug Interactions

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.

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially: Anemia or other blood problems: Patients with these problems may have an increase in side effects involving the blood, Kidney disease or, Liver disease: Patients with kidney and/or liver disease may have an increased chance of side effects, Porphyria: This medicine may cause an attack of porphyria and Seizure disorders, such as epilepsy: High doses of this medicine may increase the chance of convulsions (seizures).

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Regards

Mary Wilson

Editorial office

Clinical Pharmacology and Toxicology Research

E-mail: pharmatoxicol@eclinicalsci.com