Can sulfadoxine (antibiotic) and pyrimethamine (antiparasitic) be given to pregnant women in their second trimester for malaria prophylaxis or treatment?

Sulfadoxine and Pyrimethamine in Second Trimester Pregnancy for Malaria

Yes, sulfadoxine and pyrimethamine can be given to pregnant women in their second trimester for malaria prophylaxis or treatment, with evidence showing similar pregnancy outcomes compared to other antimalarial regimens. 1

Evidence for Safety and Efficacy in Second Trimester

The CDC guidelines provide strong evidence supporting the use of sulfadoxine-pyrimethamine (SP) during pregnancy, particularly in the second trimester:

• A Zambian cohort study found similar pregnancy outcomes between women treated with artemether-lumefantrine compared to those treated with sulfadoxine-pyrimethamine 1
• Two meta-analyses of women with malaria in the second and third trimester found no association between ACT treatment and congenital malformations or miscarriage, suggesting the relative safety of antimalarial treatments during this period 1

Dosing and Administration

For pregnant women in the second trimester, the recommended regimen for malaria prophylaxis or treatment with sulfadoxine-pyrimethamine includes:

• Pyrimethamine: 100 mg/day PO divided BID for 2 days followed by 50 mg/day PO QD 1
• Sulfadoxine: 75 mg/kg per dose PO × 1, followed by 100 mg/kg per day PO divided BID (maximum sulfadoxine = 4 g/day) 1
• Folinic acid (leucovorin): 10–20 mg/day PO QD (during and 1 week after pyrimethamine therapy) 1

Important Considerations and Precautions

Folinic Acid Supplementation

• Concurrent administration of folinic acid is STRONGLY recommended when using pyrimethamine during pregnancy to prevent folate deficiency 1, 2
• Folic acid should NOT be used as a substitute for folinic acid 1

Monitoring

• For patients receiving high dosages, semiweekly blood counts including platelet counts should be performed to monitor for bone marrow suppression 2
• Monitor for signs of anemia, as one study found higher rates of anemia in pregnant women taking certain antimalarial regimens 1

Pharmacokinetic Considerations

• Pregnancy significantly alters the pharmacokinetics of both sulfadoxine and pyrimethamine:
  • Clearance increases 3-fold for sulfadoxine during pregnancy 3
  • Pyrimethamine clearance decreases by 18% during pregnancy 3
  • These changes may affect efficacy and potentially require dose adjustments 4

Efficacy Evidence

• Studies in high-transmission areas show that SP-IPTp (intermittent preventive treatment in pregnancy) is effective in reducing placental malaria infections 5
• In one study, women who received a two-dose SP regimen had only 9% placental malaria infection at delivery compared to 32% in those receiving chloroquine regimens 5

Alternatives and Considerations

• For areas with high SP resistance, alternative regimens may be considered:
  • Mefloquine can be used in the second and third trimesters 1
  • Artemether-lumefantrine is now recommended by the CDC as an additional option for treatment during second and third trimesters 1

Potential Adverse Effects

• Pyrimethamine has been shown to be teratogenic in animal studies at doses 2.5-5 times the human dose for toxoplasmosis treatment 2
• Common adverse effects of SP include:
  • Vomiting (more common with mefloquine than SP) 6
  • Dizziness (more common with mefloquine than SP) 6
  • Potential bone marrow suppression (requiring folinic acid supplementation) 2

Clinical Decision Algorithm

1. Confirm pregnancy is in second trimester
2. Assess malaria risk and resistance patterns in the region
3. If SP is appropriate based on resistance patterns:
   • Prescribe SP with appropriate dosing
   • ALWAYS add folinic acid supplementation
   • Schedule regular blood count monitoring
4. If high SP resistance is present in the region:
   • Consider alternative regimens like mefloquine or artemether-lumefantrine
5. Monitor for adverse effects and treatment efficacy

In conclusion, sulfadoxine-pyrimethamine remains an important option for malaria prophylaxis and treatment during the second trimester of pregnancy, especially in areas where resistance is not widespread, but must always be administered with folinic acid and appropriate monitoring.