Is cotrimazole (Co-trimoxazole) contraindicated during pregnancy?

Is Cotrimoxazole Contraindicated in Pregnancy?

Cotrimoxazole is not absolutely contraindicated in pregnancy, but it should be avoided during the first trimester and near term due to risks of neural tube defects and neonatal complications; it can be used with more confidence during the second and third trimesters when clinically necessary, particularly for specific infections like Q fever. 1

Risk Profile by Trimester

First Trimester

• Avoid cotrimoxazole during the first trimester due to the theoretical risk of neural tube defects related to folate antagonism. 1
• The European Respiratory Society guidelines classify cotrimoxazole as "avoid" during pregnancy with absolute contraindications including first trimester exposure. 1
• The American Academy of Dermatology recommends avoiding cotrimoxazole particularly in the first trimester due to risks of congenital malformations. 1

Second and Third Trimesters

• Cotrimoxazole can be used with more confidence during the second and third trimesters when the risk of neural tube defects is lower and safer alternatives are unavailable. 1
• The American Academy of Dermatology notes that cotrimoxazole may be used in the second trimester when the maternal infection poses greater risk than the medication and safer alternatives have failed. 1

Near Term/At Delivery

• Avoid cotrimoxazole near term or at delivery due to the risk of neonatal hyperbilirubinemia and kernicterus. 1
• Clinicians should be aware of the risk for neonatal hyperbilirubinemia when cotrimoxazole is prescribed in the third trimester. 1

Specific Clinical Scenarios Where Cotrimoxazole Is Recommended

Q Fever in Pregnancy

• Long-term cotrimoxazole therapy (320 mg trimethoprim and 1600 mg sulfamethoxazole for 35 days) is specifically recommended for pregnant women with Q fever to decrease the risk of placentitis, obstetric complications, and maternal chronic Q fever infection. 2, 1
• This represents a situation where the benefits clearly outweigh the risks, as Q fever can cause intrauterine fetal death related to placental infection. 2
• The CDC has determined that the risk of acquiring serious infections like Q fever outweighs the risk of antimicrobial drug-related adverse effects. 1

Risk Mitigation Strategies

Folic Acid Supplementation

• All women capable of becoming pregnant should consume at least 400 μg of folic acid daily from supplements, fortified foods, or both, to reduce the risk of neural tube defects, especially if taking cotrimoxazole. 1

Alternative Antibiotics

• For most infections during pregnancy, consider safer alternatives first:
  • Oral cephalexin, azithromycin, or clindamycin are safer systemic antibiotic options during pregnancy. 1
  • For patients with penicillin allergy, macrolides (except erythromycin estolate) may be considered as alternatives. 1

Common Pitfalls to Avoid

• Do not prescribe cotrimoxazole in the first trimester unless treating a life-threatening infection with no safer alternatives (such as Q fever). 1
• Do not prescribe cotrimoxazole near term or at delivery due to kernicterus risk in the neonate. 1
• Do not use cotrimoxazole without ensuring adequate folic acid supplementation in women of childbearing age. 1
• The 2025 hidradenitis suppurativa guidelines specifically recommend avoiding oral co-trimoxazole in pregnant patients due to increased risk of preterm birth, low birthweight, and kernicterus. 1

Clinical Decision Algorithm

1. First trimester: Avoid cotrimoxazole; use alternative antibiotics unless treating Q fever or another life-threatening infection with no safer options. 1
2. Second trimester: May consider cotrimoxazole when safer alternatives have failed or are contraindicated, ensuring folic acid supplementation. 1
3. Third trimester (not near term): Can use with caution for appropriate indications with folic acid supplementation. 1
4. Near term/at delivery: Avoid due to neonatal hyperbilirubinemia risk. 1