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

Sulfadoxine and Pyrimethamine Should Not Be Given During the First Trimester of Pregnancy

Pyrimethamine is potentially teratogenic and should not be used before the 18th week of pregnancy. 1

Safety Concerns in First Trimester

Pyrimethamine, a component of the sulfadoxine-pyrimethamine (SP) combination, has significant safety concerns during early pregnancy:

• Teratogenic potential: Pyrimethamine has been shown to be teratogenic in animal studies, producing abnormalities such as cleft palate, brachygnathia, oligodactyly, and microphthalmia in rats at doses 2.5 times the human dose for toxoplasmosis treatment 2

• FDA Pregnancy Category C: The FDA classifies pyrimethamine as Pregnancy Category C, indicating potential risks to the fetus based on animal reproduction studies 2

• Specific timing restriction: Guidelines explicitly state that pyrimethamine should not be used before the 18th week of pregnancy due to its potential teratogenic effects 1

Recommended Alternatives for First Trimester

For pregnant women requiring treatment during the first trimester:

• Spiramycin: This is the recommended alternative for toxoplasmosis treatment during the first trimester as it is not teratogenic 1

  • Dose: 1g (3 million IU) orally three times daily
  • Total daily dose: 3g (9 million IU)
  • Available in the US only through the FDA's Investigational New Drug process

• Consultation recommendation: Medical consultation with specialists familiar with toxoplasmosis is strongly recommended for any treatment during pregnancy 1

When SP Can Be Used During Pregnancy

Sulfadoxine-pyrimethamine can be safely administered after the first trimester in the following scenarios:

1. For women ≥18 weeks of pregnancy when:

   • It is suspected or confirmed they acquired acute infection at or after the 18th week of pregnancy
   • A positive amniotic fluid PCR test result is documented
   • An abnormal fetal ultrasonograph is suggestive of congenital toxoplasmosis 1

2. For intermittent preventive treatment of malaria in pregnancy (IPTp-SP) after quickening (around 18-20 weeks) 3

Important Precautions When Using SP After First Trimester

When using sulfadoxine-pyrimethamine after the first trimester:

• Folinic acid supplementation: Concurrent administration of folinic acid (leucovorin) at 10-20 mg/day is strongly recommended during and for one week after pyrimethamine therapy 1, 2

• Do not substitute: Folic acid should not be used as a substitute for folinic acid 1

• Avoid concurrent use with cotrimoxazole: SP should not be administered concurrently with cotrimoxazole due to redundant mechanisms of action and synergistic worsening of adverse drug reactions 3

• Laboratory monitoring: In patients receiving high dosage, semiweekly blood counts, including platelet counts, should be performed 2

Pharmacokinetic Considerations

Pregnancy significantly alters the pharmacokinetics of both drugs:

• Sulfadoxine clearance increases 3-fold during pregnancy 4, 5
• Pyrimethamine clearance decreases by approximately 18% during pregnancy 4
• These changes result in lower plasma concentrations of both drugs, which could potentially compromise efficacy 5

Conclusion

Based on the strongest evidence from current guidelines, sulfadoxine-pyrimethamine should not be administered during the first trimester of pregnancy due to the teratogenic potential of pyrimethamine. Treatment with SP should be delayed until after 18 weeks of gestation when necessary, with appropriate monitoring and concurrent folinic acid supplementation.