What anti-tuberculosis (TB) medications are safe to use during pregnancy?

Safe Anti-Tuberculosis Drugs During Pregnancy

Isoniazid, rifampin, and ethambutol are the first-line anti-tuberculosis drugs that are considered safe for use during pregnancy, while streptomycin should be avoided due to its risk of fetal ototoxicity. 1

First-Line Anti-TB Drugs in Pregnancy

Safe Options

• Isoniazid (INH):

  • Considered safe during pregnancy 1, 2
  • Crosses the placenta but not associated with human fetal malformations 3
  • Should be administered with pyridoxine (vitamin B6) 25mg/day to prevent peripheral neuropathy 1
  • Requires monitoring of liver function tests due to risk of hepatotoxicity

• Rifampin (RIF):

  • Crosses the placenta but has not been shown to have teratogenic effects 1
  • Safe to use during pregnancy 1
  • May reduce efficacy of oral contraceptives due to enzyme induction

• Ethambutol (EMB):

  • Considered safe for use in pregnancy 1
  • No demonstrated teratogenic effects in humans 1, 4
  • Can be used without undue concern 5

Drugs to Use with Caution

• Pyrazinamide (PZA):
  • WHO and IUATLD recommend routine use in pregnant women 1
  • Not routinely recommended in the United States due to insufficient safety data 1
  • Some public health jurisdictions in the US have used it without reported adverse events 1
  • If not included, treatment duration should be extended to 9 months

Drugs to Avoid

• Streptomycin:

  • Should NOT be used during pregnancy 1
  • Documented harmful effects on human fetus - interferes with ear development 1
  • Can cause congenital deafness in approximately 17% of exposed babies 1

• Other aminoglycosides (kanamycin, amikacin) and capreomycin:

  • Presumed to share streptomycin's ototoxic potential 1
  • Should be avoided during pregnancy

Treatment Regimens During Pregnancy

Recommended Initial Regimen

The initial treatment regimen for pregnant women with tuberculosis should consist of:

• Isoniazid (INH)
• Rifampin (RIF)
• Ethambutol (EMB) 1

If pyrazinamide is not included, treatment should be extended to a minimum of 9 months 1.

Special Considerations

1. Breastfeeding:

   • First-line agents (INH, RIF, EMB) pass into breast milk in small amounts but do not produce toxic effects in nursing infants 1
   • Breastfeeding should not be discouraged for women on first-line agents 1
   • Supplementary pyridoxine is recommended for both nursing mother and infant if the mother is taking INH 1

2. Monitoring:

   • Regular liver function tests are essential, especially with INH
   • Monthly clinical evaluations for adverse effects
   • Patient education about potential side effects to decrease maternal morbidity 6

3. Timing of Treatment:

   • Treatment should be started as soon as tuberculosis is diagnosed 6
   • Delaying treatment poses significant risks to both mother and fetus 3

Second-Line Drugs in Pregnancy

For drug-resistant TB, treatment options are more limited:

• Fluoroquinolones:

  • Associated with arthropathies in young animals
  • Should be avoided if possible during pregnancy 1
  • Ciprofloxacin has the best safety profile among second-line drugs if needed for drug-resistant TB 3

• Ethionamide:

  • Limited data, but one report described nonspecific teratogenic effects 1
  • Should be avoided when possible

• Cycloserine:

  • Insufficient data to determine safety in pregnancy 1

Important Considerations

1. Counseling: Women being treated for drug-resistant TB should receive counseling about the risks to the fetus due to the known and unknown risks of second-line agents 1

2. Abortion: Routine therapeutic abortion is not medically indicated for pregnant women taking first-line anti-TB drugs 5

3. Supervised Treatment: Adherence to treatment can be especially difficult during pregnancy due to fear of medication effects and pregnancy-related nausea. Directly observed therapy (DOT) is particularly helpful in encouraging adherence 3

4. Treatment Timing: Treatment should not be delayed as untreated tuberculosis poses a significant threat to the mother, fetus, and family 3

By following these guidelines, tuberculosis during pregnancy can be effectively treated while minimizing risks to both mother and baby.