Hydrocortisone suspension and hydrocortisone tablets are not bioequivalentin the treatment of children with congenital adrenal hyperplasia

In July 1998, Cortef oral suspension (Pharmacia & Upjohn) was reformulated changing the suspending agent tragacanth to xanthan gum. We subsequently ob served suboptimal control of hormone levels in a group of children with cla ssic congenital adrenal hyperplasia, despite increasing doses of Cortef sus pension and stringent instructions to parents regarding shaking of the bott les of medication. Nineteen children receiving Cortef and fludrocortisone t herapy were changed to hydrocortisone tablets and fludrocortisone, with a 1 0 percent reduction in hydrocortisone dose. A significant decrease in 17-hy droxyprogesterone (235 +/- 120 vs. 27 +/- 7 nmol/L; p less than or equal to 0.001) and androstenedione (18.9 +/- 18.0 vs. 3.5 +/- 3.5 nmol/L; p=0.002) was observed 4-6 weeks later. Twenty-one percent (4/19) had 17-hydroxyproge sterone and androstenedione levels at or below the detection limit of the a ssay. Despite a significant reduction in glucocorticoid dose (19.6 +/- 4.7 vs. 17.6 +/- 3.9 mg/M-2/day; p<0.001), eight children experienced significa nt weight gain and appetite increase, three experienced trouble sleeping, f our experienced moodiness, and three developed hypertension requiring a dec rease in fludrocortisone therapy. Hydrocortisone dose was further decreased to 15.2 +/- 2.6 mg/M-2/day with resolution of symptoms. We conclude that C ortef suspension and hydrocortisone tablets are not bioequivalent and the r eformulated form of hydrocortisone oral suspension was inadequate in the co ntrol of children with congenital adrenal hyperplasia. Cortef suspension ha s been recalled as a result of these data.