8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no available data on RELYVRIO use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal studies, administration of sodium phenylbutyrate and taurursodiol to rats throughout pregnancy and lactation resulted in increased offspring mortality at all doses tested, which were less than or similar to the clinical doses.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

Oral administration of the combination of sodium phenylbutyrate and taurursodiol (0, 375, 750, or 1500 mg/kg/day, containing sodium phenylbutyrate and taurursodiol in a 3:1 ratio) to pregnant mice during the period of organogenesis was not associated with any adverse effects. At the highest dose of the combination of sodium phenylbutyrate and taurursodiol tested, the doses of sodium phenylbutyrate and taurursodiol were similar to the maximum recommended dose (6 g sodium phenylbutyrate and 2 g taurursodiol) in humans (MRHDs), based on body surface area (mg/m2).

Oral administration of the combination of sodium phenylbutyrate and taurursodiol (0, 375, 750, or 1500 mg/kg/day) to pregnant rats during the period of organogenesis was not associated with any adverse effects. At the highest dose of the combination of sodium phenylbutyrate and taurursodiol tested, the doses of sodium phenylbutyrate and taurursodiol were approximately 2-fold the MRHDs, based on mg/m2.

Oral administration of the combination of sodium phenylbutyrate and taurursodiol (0, 375, 750, or 1500 mg/kg/day) to rats throughout pregnancy and lactation resulted in increases in stillbirth at all doses and pup deaths at the highest dose tested. A no effect dose for adverse developmental effects in rats was not identified. At the lowest dose of the combination of sodium phenylbutyrate and taurursodiol tested, the doses of sodium phenylbutyrate and taurursodiol were less than the MRHDs, based on mg/m2.

8.2 Lactation

Risk Summary

There are no data on the presence of sodium phenylbutyrate or taurursodiol in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RELYVRIO and any potential adverse effects on the breastfed child from RELYVRIO or from the underlying maternal condition.

8.4 Pediatric Use

Safety and effectiveness of RELYVRIO in pediatric patients have not been established.

8.5 Geriatric Use

Of the 89 patients with ALS who received RELYVRIO in Study 1, 25 patients (28%) were 65 years of age or older, while 4 patients (4.5%) were 75 years of age and older with the oldest patient being 79 years old.

No overall differences in safety or effectiveness were observed between those patients 65 years of age and older and those <65 years of age. Although differences in responses between the elderly and younger patients were not identified, greater sensitivity of some older individuals cannot be ruled out.

8.6 Renal Impairment

No dose adjustment is needed for patients with mild renal impairment. Avoid use in patients with moderate or severe renal impairment [see Clinical Pharmacology (12.3)].

8.7 HepaticImpairment

No dose adjustment is needed for patients with mild hepatic impairment. Avoid use in patients with moderate or severe hepatic impairment [see Clinical Pharmacology (12.3)].