Phenobarbital Interactions

Phenobarbital activates the pregnane X receptor and constitutive androstane receptor, strongly inducing hepatic CYP3A4 while also directly suppressing CYP27A1 (a 25-hydroxylase), so it both accelerates breakdown of 25-hydroxyvitamin D and slows its formation; serum 25(OH)D drops substantially over weeks to months of therapy, with osteomalacia and increased fracture risk documented in long-term users.