FANSIDAR
Clinical safety rating
cautionComprehensive clinical and safety monograph for FANSIDAR (FANSIDAR).
Fansidar combines sulfadoxine, a sulfonamide dihydrofolate reductase inhibitor, and pyrimethamine, a dihydrofolate reductase inhibitor, synergistically inhibiting folate synthesis in Plasmodium species, leading to nucleic acid synthesis inhibition and parasite death.
| Metabolism | Sulfadoxine is primarily metabolized by N-acetyltransferase (NAT) to N-acetylsulfadoxine; pyrimethamine is metabolized by hepatic microsomal enzymes, including CYP2C9 and CYP3A4. Both are excreted renally. |
| Excretion | Renal: sulfadoxine 80% (unchanged), pyrimethamine 20-40% (unchanged); fecal: sulfadoxine <5%, pyrimethamine <5% |
| Half-life | Sulfadoxine: 100-200 hours; pyrimethamine: 80-100 hours; clinical context: unusual for antimalarials, allows single-dose therapy for uncomplicated P. falciparum |
| Protein binding | Sulfadoxine: 90-95% bound to albumin; pyrimethamine: 70-80% bound to albumin and globulins |
| Volume of Distribution | Sulfadoxine: 1.5-2.0 L/kg (distributes widely including CSF); pyrimethamine: 2.0-3.0 L/kg (extensive tissue distribution) |
| Bioavailability | Oral: sulfadoxine >85%, pyrimethamine >90%; IM: essentially 100% |
| Onset of Action | Oral: 2-4 hours; parenteral (IM): 30-60 minutes |
| Duration of Action | 3-4 weeks; single oral dose provides prophylaxis for 1-4 weeks due to long half-lives |
| Molecular Weight | 198.16 |
For acute uncomplicated malaria: 3 tablets (25 mg pyrimethamine + 500 mg sulfadoxine per tablet) orally as a single dose on Day 0 and Day 1 (total 6 tablets); alternatively, 3 tablets as a single dose. For severe malaria: 3 tablets orally as a single dose, repeated at weekly intervals if necessary.
| Dosage form | TABLET |
| Renal impairment | CrCl 10-50 mL/min: no adjustment recommended. CrCl <10 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B or C: avoid use due to risk of hepatotoxicity and accumulation. |
| Pediatric use | Weight-based single dose: 5-10 kg: 1/4 tablet; 11-20 kg: 1/2 tablet; 21-30 kg: 3/4 tablet; 31-45 kg: 1 tablet; >45 kg: 2 tablets. Administer orally, repeat on Day 1 if indicated. |
| Geriatric use | No specific dose adjustment recommended, but monitor renal function closely due to age-related decline; sulfadoxine-pyrimethamine is generally well-tolerated in elderly, but caution with hepatic or renal impairment. |
| 1st trimester | Contraindicated: teratogenic effects (sulfadoxine/pyrimethamine) including neural tube defects and cardiovascular malformations. |
| 2nd trimester | Contraindicated: potential for kernicterus from sulfonamide in third trimester, but use in second trimester may be considered if benefit outweighs risk; generally avoided. |
| 3rd trimester | Contraindicated: risk of bilirubin displacement leading to kernicterus; avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for FANSIDAR (FANSIDAR).
| Placental transfer | Both drugs cross the placenta; sulfadoxine reaches fetal concentrations ~50% of maternal; pyrimethamine also crosses, with teratogenic potential. |
| Breastfeeding | Both sulfadoxine and pyrimethamine are excreted into breast milk in small amounts. Risk of hemolytic anemia in G6PD-deficient infants and kernicterus in premature or hyperbilirubinemic infants. Avoid in breastfeeding unless no safer alternative. |
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | Pregnancy Category C. First trimester: Contraindicated due to sulfadoxine-pyrimethamine's antifolate activity, associated with neural tube defects and major congenital malformations (anencephaly, cleft palate) based on animal studies and human case reports. Second and third trimesters: Use only if benefit outweighs risk; no adequate human studies show fetal harm in later trimesters, but theoretical risk of kernicterus in neonate due to sulfadoxine displacement of bilirubin, especially if near term. |
| Fetal Monitoring | Monitor complete blood count (CBC) with differential and platelets, liver function tests (LFTs), and renal function monthly. Assess for hypersensitivity reactions, including Stevens-Johnson syndrome. In pregnancy, monitor fetal growth and amniotic fluid index with ultrasound if used in second/third trimester. Monitor for neonatal jaundice and hemolysis after delivery. |
| Fertility Effects | No known direct impairment of fertility in humans. In animal studies, high-dose pyrimethamine caused testicular atrophy. Theoretical antifolate effect may impair spermatogenesis or oogenesis, but clinical significance is negligible at standard doses. |
■ FDA Black Box Warning
Fatalities due to severe adverse reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias have been reported. Fansidar should not be used for malaria prophylaxis due to the risk of severe skin reactions.
| Serious Effects |
Hypersensitivity to sulfonamides or pyrimethamineChronic alcohol use or liver diseasePorphyriaKnown G6PD deficiencyInfants less than 2 months of ageDuring pregnancy (especially first and third trimesters)
| Precautions | Severe cutaneous adverse reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), hematologic toxicity (agranulocytosis, aplastic anemia), hepatic toxicity, hypersensitivity reactions, and photosensitivity. Monitor for skin reactions, blood dyscrasias, and hepatic function. |
| Food/Dietary | Avoid alcohol during treatment to reduce hepatotoxicity risk. High-fat meals may slightly increase pyrimethamine absorption; maintain consistent diet. Do not take with folic acid supplements as they may antagonize the drug's antifolate effect. Avoid excessive caffeine consumption; pyrimethamine may increase caffeine levels. |
| Clinical Pearls | Fansidar (sulfadoxine/pyrimethamine) is a fixed-dose combination antifolate used for malaria prophylaxis and treatment. Due to severe adverse reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), it is no longer recommended for prophylaxis in travelers; reserved for chloroquine-resistant Plasmodium falciparum malaria when other agents are unavailable. Administer with food to reduce GI upset. Monitor for hypersensitivity, especially in patients with sulfonamide allergy. Not effective against P. vivax or P. ovale. Consider G6PD deficiency screening before use. |
| Patient Advice | Take with a full glass of water and with food to prevent stomach upset. · Complete the full course even if symptoms improve. · Seek immediate medical attention for rash, blisters, mouth sores, or fever—these could signal a severe skin reaction. · Avoid prolonged sun exposure and use sunscreen; photosensitivity may occur. · Inform your doctor of all medications, especially methotrexate, warfarin, or antiepileptics. · Not recommended for pregnant women or nursing mothers unless specifically advised by a physician. · Do not take if you have a sulfa allergy or history of folic acid deficiency anemia. · Store at room temperature away from moisture and heat. |
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