Rifapentine reached breast milk at very low levels

Design

Model-based pharmacokinetic analysis of a prospective study (IMPAACT 2001)

Population

Pregnant and postpartum women on weekly isoniazid-rifapentine, and their infants

Primary outcome

Breast milk, cord blood and infant plasma concentrations

Effect

Milk:plasma ratio 0.024; relative infant dose <1%

IMPAACT 2001 studied once-weekly isoniazid plus rifapentine for tuberculosis prevention in pregnant and postpartum women. This model-based analysis used rifapentine and its active metabolite measured in maternal plasma, breast milk, cord blood and infant plasma. Published in Clinical Pharmacology & Therapeutics on 15 October 2026.

Breast milk concentrations were about 2% of maternal plasma for rifapentine and 4% for desacetyl-rifapentine, with rapid equilibration. The maximum relative infant dose was estimated below 1%, well under the 10% level usually taken as a threshold for concern. Rifapentine did cross the placenta: cord blood levels were about 28% of maternal plasma, and infant plasma about 61% within 72 hours of a maternal dose, levels the authors judged unlikely to be clinically significant.

Short rifapentine-based regimens are increasingly used for TB preventive therapy, including in India's programme. Lactating women are often excluded or advised to stop breastfeeding for lack of data.

These are pharmacokinetic findings from a modest sample, not long-term infant outcome data, but they support continuing breastfeeding.

• Do not advise stopping breastfeeding solely because a mother is on weekly isoniazid-rifapentine
• Give pyridoxine to the mother on isoniazid, and consider it for the breastfed infant as per local guidance
• Expect orange discoloration of breast milk, urine and tears, and warn the mother
• Check hormonal contraception: rifapentine induces enzymes and can reduce its effect

Why it matters

Lactation need not be a reason to delay TB preventive therapy or to stop breastfeeding.

Don't overread it

These are concentration data; they do not measure infant outcomes directly.

The statistics, in plain English

The relative infant dose compares what a breastfed baby receives with the mother's weight-adjusted dose. Under 1% is very low; most drugs considered compatible with breastfeeding are under 10%.

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