No

Antimalarial Agent

Treatment of Plasmodium falciparum malaria in patients in whom chloroquine resistance is suspected; malaria prophylaxis for travelers to areas where chloroquine-resistant malaria is endemic

C

Known hypersensitivity to any sulfa drug, pyrimethamine, or any component; porphyria, megaloblastic anemia, severe renal insufficiency; children <2 months of age due to competition with bilirubin for protein binding sites

Use with caution in patients with renal or hepatic impairment, patients with possible folate deficiency, and patients with seizure disorders, increased adverse reactions are seen in patients also receiving chloroquine; fatalities associated with sulfonamides, although rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias; discontinue use at first sign of rash or any sign of adverse reaction; hemolysis occurs in patients with G-6-PD deficiency; leucovorin should be administered to reverse signs and symptoms of folic acid deficiency

>10%:

Central nervous system: Ataxia, seizures, headache

Dermatologic: Photosensitivity

Gastrointestinal: Atrophic glossitis, vomiting, gastritis

Hematologic: Megaloblastic anemia, leukopenia, thrombocytopenia, pancytopenia

Neuromuscular & skeletal: Tremors

Miscellaneous: Hypersensitivity

1% to 10%:

Dermatologic: Stevens-Johnson syndrome

Hepatic: Hepatitis

<1%: Erythema multiforme, toxic epidermal necrolysis, rash, thyroid function dysfunction, anorexia, glossitis, crystalluria, hepatic necrosis, respiratory failure

Symptoms of overdose include anorexia, vomiting, CNS stimulation including seizures, megaloblastic anemia, leukopenia, thrombocytopenia, crystalluria

Leucovorin should be administered in a dosage of 3-9 mg/day for 3 days or as required to reverse symptoms of folic acid deficiency; doses of as little as 2-5 g/day may produce toxicity; the aniline radical is responsible for hematologic toxicity; high volume diuresis may aid in elimination and prevention of renal failure; diazepam can be used to control seizures

Decreased effect with PABA or PABA metabolites of local anesthetics

Increased toxicity with methotrexate, other sulfonamides, co-trimoxazole

Protect from light

Sulfadoxine interferes with bacterial folic acid synthesis and growth via competitive inhibition of para-aminiobenzoic acid; pyrimethamine inhibits microbial dihydrofolate reductase, resulting in inhibition of tetrahydrofolic acid synthesis

Absorption: Oral: Well absorbed

Distribution:

Pyrimethamine: Widely distributed; mainly concentrated in blood cells, kidneys, lungs, liver, and spleen

Sulfadoxine: Well distributed like other sulfonamides

Metabolism: Pyrimethamine: Hepatic; Sulfadoxine: None

Half-life: Pyrimethamine: 80-95 hours; Sulfadoxine: 5-8 days

Time to peak serum concentration: Within 2-8 hours

Elimination: Excreted in urine as parent compounds and several unidentified metabolites

Children and Adults: Oral:

2-11 months: 1/4 tablet

1-3 years: 1/2 tablet

4-8 years: 1 tablet

9-14 years: 2 tablets

>14 years: 2-3 tablets

Malaria prophylaxis:

The first dose of Fansidar® should be taken 1-2 days before departure to an endemic area (CDC recommends that therapy be initiated 1-2 weeks before such travel), administration should be continued during the stay and for 4-6 weeks after return. Dose = pyrimethamine 0.5 mg/kg/dose and sulfadoxine 10 mg/kg/dose up to a maximum of 25 mg pyrimethamine and 500 mg sulfadoxine/dose weekly.

2-11 months: 1/8 tablet once weekly or1/4 tablet once every 2 weeks

1-3 years: 1/4 tablet once weekly or1/2 tablet once every 2 weeks

4-8 years: 1/2 tablet once weekly or 1 tablet once every 2 weeks

9-14 years: 3/4 tablet once weekly or1 1/2 tablets once every 2 weeks

>14 years: 1 tablet once weekly or 2 tablets once every 2 weeks

CBC, including platelet counts, and urinalysis should be performed periodically

Sulfonamides reported to cause restlessness, irritability, depression, euphoria, disorientation, panic, hallucinations, and delusions

Photosensitivity is common; use caution with concurrent psychotropics; may cause leukopenia; caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Begin prophylaxis at least 2 days before departure; drink plenty of fluids; avoid prolonged exposure to the sun; notify physician if rash, sore throat, pallor, or glossitis occurs

Tablet: Sulfadoxine 500 mg and pyrimethamine 25 mg

Lynk A and Gold R, "Review of 40 Children With Imported Malaria," Pediatr Infect Dis J, 1989, 8(11):745-50.

Panisko DM and Keystone JS, "Treatment of Malaria - 1990," Drugs, 1990, 39(2):160-89.

Randall G and Seidel JS, "Malaria," Pediatr Clin North Am, 1985, 32(4):893-916.

Wyler DJ, "Malaria Chemoprophylaxis for the Traveler," N Engl J Med, 1993, 329(1):31-7.

Wyler DJ, "Malaria: Overview and Update," Clin Infect Dis, 1993, 16(4):449-56.