Warren Grant Magnuson Clinical Center (D.P.M., D.C., K.A.C.), Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development (D.P.M., M.F.K., G.P.C.), National Institutes of Health, Bethesda, Maryland
Abstract
In July 1998, Cortef oral suspension (Pharmacia & Upjohn) was
reformulated changing the suspending agent tragacanth to xanthan gum.
We subsequently observed suboptimal control of hormone levels in a
group of children with classic congenital adrenal hyperplasia, despite
increasing doses of Cortef suspension and stringent instructions to
parents regarding shaking of the bottles of medication. Nineteen
children receiving Cortef and fludrocortisone therapy were changed to
hydrocortisone tablets and fludrocortisone, with a 10 percent reduction
in hydrocortisone dose. A significant decrease in
17-hydroxyprogesterone (235 ± 120 vs. 27 ± 7 nmol/L;
p0.001) and androstenedione (18.9 ± 18.0 vs. 3.5 ± 3.5
nmol/L; p=0.002) was observed 46 weeks later. Twenty-one percent
(4/19) had 17-hydroxyprogesterone and androstenedione levels at or
below the detection limit of the assay. Despite a significant reduction
in glucocorticoid dose (19.6 ± 4.7 vs. 17.6 ± 3.9
mg/M2/day; p<0.001), eight children experienced
significant weight gain and appetite increase, three experienced
trouble sleeping, four experienced moodiness, and three developed
hypertension requiring a decrease in fludrocortisone therapy.
Hydrocortisone dose was further decreased to 15.2 ± 2.6
mg/M2/day with resolution of symptoms. We conclude that
Cortef suspension and hydrocortisone tablets are not bioequivalent and
the reformulated form of hydrocortisone oral suspension was inadequate
in the control of children with congenital adrenal hyperplasia. Cortef
suspension has been recalled as a result of these data.