Sulfadoxine/pyrimethamine

Combination of
Sulfadoxine	Sulfonamide
Pyrimethamine	Antiparasitic
Clinical data
Trade names	Fansidar
Licence data	US FDA:link
Pregnancy category	AU: C US: C (Risk not ruled out)
Legal status	AU: S4 (Prescription only) UK: POM (Prescription only) US: ℞-only
Routes of administration	Oral
Identifiers
ATC code	P01BD51 (WHO)
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Sulfadoxine/pyrimethamine (Fansidar) is a combination antimalarial drug containing the sulfonamide antibiotic sulfadoxine and the antiprotozoal pyrimethamine.

It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.

Medical uses

Malaria

It is approved by the United States' Food and Drug Administration for use as a treatment and preventive measure against malaria. 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. Due to side effects, however, it is no longer recommended as a routine preventive, but only to treat serious malaria infections or to prevent them in areas where other drugs may not work.

Other

It has also be used as a treatment and prophylactic measure for toxoplasmosis and Pneumocystis jiroveci pneumonia.

Adverse effects

Adverse effects by incidence include:

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):

• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Agranulocytosis
• Aplastic anaemia
• Disorder of haematopoietic structure
• Drug-induced eosinophilia
• Thrombocytopaenia
• Liver necrosis
• Hepatitis
• Jaundice
• Hepatomegaly
• Nephrotoxicity

Unknown frequency:

• Weight loss
• Abdominal cramps
• Hair loss
• Photosensitivity
• Fatigue
• Fever
• Polyneuritis
• Atrophic glossitis
• Gastritis

• Abnormal liver function test results (e.g. elevated serum ALT, AST, alkaline phosphatase, and bilirubin concentrations)

Contraindications

Use of this drug is contraindicated in:

• 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. Pyrimethamine serves as a selective inhibitor of protozoal dihydrofolate reductase, hence preventing the synthesis of tetrahydrofolate — the active form of folate. A great degree of synergy occurs between the two drugs due to their inhibition of two different steps in the biosynthesis of tetrahydrofolate.

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

See also

• Pyrimethamine
• Sulfadoxine
• Trimethoprim/sulfamethoxazole (co-trimoxazole)