Can sulfadoxine and pyrimethamine be given during the second trimester of pregnancy?

Sulfadoxine and Pyrimethamine Use During Second Trimester of Pregnancy

Pyrimethamine is potentially teratogenic and should not be used before the 18th week of pregnancy, but sulfadoxine-pyrimethamine combination can be safely administered after 18 weeks gestation (during the second trimester) for appropriate indications. 1

Safety and Timing Guidelines

Pyrimethamine Safety in Pregnancy

• Pyrimethamine has been shown to be teratogenic in animal studies when given at doses 2.5 times the human dose for toxoplasmosis treatment 2
• Animal studies demonstrated abnormalities such as cleft palate, brachygnathia, oligodactyly, and microphthalmia 2
• Critical timing restriction: Pyrimethamine should not be used before the 18th week of pregnancy due to potential teratogenic effects 1

Appropriate Use During Second Trimester

• Sulfadoxine-pyrimethamine combination can be safely administered after 18 weeks gestation (mid-second trimester) 1
• For toxoplasmosis treatment: Recommended for pregnant women ≥18 weeks of pregnancy when:
  1. Acute infection is suspected or confirmed at/after 18th week
  2. Positive amniotic fluid PCR test is documented
  3. Abnormal fetal ultrasonograph suggests congenital toxoplasmosis 1

Dosing Recommendations for Toxoplasmosis Treatment

When treating toxoplasmosis after 18 weeks gestation:

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

Important Precautions and Monitoring

Critical Precautions

• Folinic acid (leucovorin) must be administered concurrently with pyrimethamine to prevent bone marrow suppression 1, 2
• Folic acid should NOT be used as a substitute for folinic acid 1
• Sulfadiazine should not be used alone 1
• Monitor for potential hematologic toxicity: perform semiweekly blood counts, including platelet counts, for patients receiving high dosage 2

Drug Interactions

• Avoid concurrent use with other antifolic drugs or agents associated with myelosuppression 2
• Caution with concomitant use of drugs that may increase risk of bone marrow suppression 2
• Sulfadoxine may potentiate the effect of oral hypoglycemics 3

Special Considerations for Malaria Prevention

For malaria prevention during pregnancy (IPTp-SP):

• Sulfadoxine-pyrimethamine has been shown to be safe when administered in the second and third trimesters 4
• Pregnancy alters the pharmacokinetics of both drugs:
  • Sulfadoxine clearance increases 3-fold during pregnancy 5
  • Pyrimethamine clearance decreases by approximately 18% during pregnancy 5
• Women who receive ≥3 doses of SP during pregnancy are more likely to give birth at term and have normal weight babies 6

Common Pitfalls to Avoid

1. Timing error: Never administer pyrimethamine before 18 weeks gestation
2. Omitting folinic acid: Always co-administer folinic acid with pyrimethamine
3. Substituting folic acid: Never substitute regular folic acid for folinic acid
4. Drug interactions: Avoid concurrent use with other folate antagonists
5. Inadequate monitoring: Regular blood count monitoring is essential during treatment

By following these guidelines, sulfadoxine-pyrimethamine can be safely and effectively administered during the second trimester of pregnancy after 18 weeks gestation when clinically indicated.