What is the recommended treatment for tuberculosis in pregnancy?

Tuberculosis in Pregnancy

Recommended Treatment Regimen

Pregnant women with active tuberculosis should be treated immediately with isoniazid, rifampin, and ethambutol for the initial phase, as untreated tuberculosis poses a far greater risk to both mother and fetus than the medications themselves. 1, 2

Standard First-Line Therapy

• Initial phase (2 months): Isoniazid, rifampin, and ethambutol should be administered daily 1, 2

  • Isoniazid: 5 mg/kg (up to 300 mg) daily 3
  • Rifampin: 10 mg/kg daily (450 mg if <50 kg, 600 mg if ≥50 kg) 3
  • Ethambutol: 15 mg/kg daily 3

• Continuation phase (4-7 months): Isoniazid and rifampin daily 1, 2

  • Total treatment duration: 9 months minimum if pyrazinamide is not used 1, 2

• Pyridoxine (vitamin B6) 25 mg daily is mandatory for all pregnant women receiving isoniazid to prevent neurotoxicity 1, 2, 4

Critical Medications to Avoid

Streptomycin and all aminoglycosides (kanamycin, amikacin) are absolutely contraindicated in pregnancy as they cause congenital deafness in approximately 17% of exposed fetuses 1, 2, 5

• Pyrazinamide is generally not recommended in U.S. pregnancy guidelines due to insufficient teratogenicity data, though WHO recommends its use internationally 1, 2
• Ethionamide and prothionamide should be avoided as they may be teratogenic 1
• Fluoroquinolones should be avoided if possible due to arthropathy concerns in animal studies 2

Key Clinical Principles

Timing of Treatment Initiation

• Treatment should never be delayed due to pregnancy alone, even in the first trimester, particularly for women at high risk of progression (HIV-infected or recently infected) 1, 2
• For lower-risk women, some experts suggest waiting until after the first trimester, but this must be weighed against disease severity 1
• Pregnancy is not an indication for termination when taking first-line antituberculosis drugs 1, 5

Safety Profile of First-Line Drugs

The evidence consistently demonstrates that isoniazid, rifampin, and ethambutol have excellent safety records in pregnancy:

• None of the first-line drugs (isoniazid, rifampin, ethambutol) are proven teratogens in humans 1, 4, 5, 6
• All cross the placenta but do not cause fetal malformations at standard doses 1, 4
• The risk of untreated tuberculosis far exceeds any theoretical medication risks 2, 4, 6

Monitoring Requirements

Close hepatic monitoring is essential, as pregnancy may increase vulnerability to isoniazid hepatotoxicity:

• Obtain baseline liver function tests (AST/ALT, bilirubin) before starting treatment 2
• Monitor liver enzymes regularly, particularly during the first 2 months 1
• Educate patients about hepatitis symptoms and instruct them to stop medications and seek immediate evaluation if symptoms develop 1

Important Drug Interactions

Rifampin significantly reduces the effectiveness of oral contraceptives through enzyme induction 1:

• Counsel patients about contraceptive failure risk 1
• Alternative or additional contraceptive methods should be recommended 1
• Rifampin also increases metabolism of corticosteroids, methadone, and antiretroviral drugs 1, 4

Breastfeeding Considerations

Breastfeeding should not be discouraged for women on first-line antituberculosis therapy:

• Small drug concentrations in breast milk do not cause toxicity in nursing infants 1, 2
• However, drugs in breast milk are insufficient to treat or prevent tuberculosis in the infant 1, 2
• Continue pyridoxine 25 mg daily while breastfeeding 1

Special Situations

Multidrug-Resistant Tuberculosis (MDR-TB)

MDR-TB in pregnancy requires expert consultation and individualized treatment based on susceptibility testing 2, 7:

• Treatment must balance maternal survival against potential fetal risks 7
• Second-line agents have less safety data but may be necessary 7
• Case reports demonstrate successful outcomes with carefully selected regimens including capreomycin, levofloxacin, and pyrazinamide after the first trimester 7

HIV Co-infection

• Use the same standard regimen (isoniazid, rifampin, ethambutol) 2
• Ensure pyridoxine supplementation 2
• Be aware of significant drug interactions between rifampin and protease inhibitors 1

Common Pitfalls to Avoid

• Do not delay treatment waiting for "safer" trimesters—untreated tuberculosis causes maternal mortality, preterm delivery, low birth weight, and perinatal transmission 2, 4, 6
• Do not use streptomycin under any circumstances in pregnancy 1, 2, 5
• Do not forget pyridoxine supplementation—this is mandatory, not optional 1, 2, 4
• Do not assume drugs in breast milk treat the infant—the baby needs separate evaluation and management 1, 2
• Do not use 6-month regimens if pyrazinamide is omitted—extend to 9 months minimum 1, 2