Pyrimethamine + Sulfadoxine
Indications
Pyrimethamine + Sulfadoxine is used for:
Chloroquine-resistant falciparum malaria
Adult Dose
Oral
Chloroquine resistant falciparum malaria acute attack
Adult: Per tab contains pyrimethamine 25 mg and sulfadoxine 500 mg: 2-3 tabs as a single dose.
Do not repeat for at least 7 days.
Malaria Prophylaxis
1 tablet qWeek OR 2 tablets q2Weeks
Hepatic impairment: Dose reduction may be needed. Severe: contra-indicated.
Child Dose
Oral
Chloroquine resistant falciparum malaria acute attack
Child: Pyrimethamine 25mg + Sulfadoxine 500mg (Tablet):
<2 yr (5-10 kg): ½ tab as a single dose;
2-5 yr (>10-20 kg): 1 tab as a single dose;
5-10 yr (< 20-30 kg): 1½ tab as a single dose;
10-14 yr (> 30-45 kg): 2 tab as a single dose.
Do not repeat for at least 7 days.
Malaria Prophylaxis
5-10 kg: 0.25 tablet
11-20 kg: 0.5 tablet
21-30 kg: 0.75 tablet
31-45 kg: 1 tablet
>45 kg: 1.5 tablet
Renal Dose
Renal impairment: Dose reduction may be needed. Severe: contra-indicated.
Administration
Swallow tablet whole with plenty of fluids after a meal
Maintain adequate fluid intake to avert crystalluria or stone formation
Prophylaxis: take 1st dose 1-2 days before arrival to endemic area, continue throughout stay & 4-6 weeks after return
Contra Indications
Severe renal or hepatic impairment, blood dyscrasias, hypersensitivity to components, megaloblastic anaemia due to folate deficiency, pregnancy at term and during lactation, infants ? 2 mth old.
Precautions
Impaired renal or hepatic function, folate deficiency, severe allergy or bronchial asthma, G6PD deficiency, pregnancy. Take with plenty of water to prevent crystalluria. Avoid excessive exposure to sun. Discontinue at the first sign of rash. Discontinue if signs of folic acid deficiency develops. Regular CBC monitoring, LFT, analysis of urine for crystalluria when admin for > 3 mth. Take with food to minimise Gi effects (e.g. anorexia and vomiting).
Lactation: enters breast milk, contraindicated
Pregnancy-Lactation
Pregnancy Category: C
Lactation: enters breast milk, contraindicated
Interactions
Increased halofantrine and chlorpromazine levels. Increased effects of warfarin.
Potentially Fatal: Increased risk of myelosupression with zidovudine, clozapine.
Adverse Effects
Side effects of Pyrimethamine + Sulfadoxine :
Urticaria, serum sickness, photosensitisation, arthralgia, nausea, vomiting, abdominal pain, diarrhoea, headache, peripheral neuritis, ataxia, tinnitus, vertigo, convulsions, toxic nephrosis and pulmonary infiltrates resembling eosinophilic or allergic alveolitis.
Potentially Fatal: Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, blood dyscrasias, anaphylactoid reactions.
Mechanism of Action
Pyrimethamine, a folic acid antagonist, inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid (folinic acid). Sulfadoxine, a structural analog of p-aminobenzoic acid (PABA), competitively inhibits dihydrofolic acid synthesis which is important for PABA conversion to folic acid. This combination results in a synergistic action against susceptible plasmodia. Both have prolonged half-lives enabling single dose admin.