Supprelin LA (histrelin acetate)
Company: Indevis Pharms
Approval Status: Approved May 2007
Treatment for: central precocious puberty
Areas: Endocrinology; Pediatrics/Neonatology
| General Information | Clinical Results | Side Effects | Mechanism of Action | Literature References | Additional Information |
General Information
Supprelin LA is a GnRH agonist and an inhibitor of gonadotropin secretion when given continuously. It desensitizes responsiveness of the pituitary gonadotropin which, in turn causes a reduction in ovarian and testicular steroidogenesis.
Supprelin LA is specifically indicated for the treatment of children with central precocious puberty (CPP).
Supprelin LA is supplied as an implant for continuous release over the course of 12 months. The recommended initial dose of the drug is one implant every 12 months.
Clinical Results
FDA Approval
FDA approval of Supprelin LA is based on the results of two
open-label, single arm clinical studies. Study 1 enrolled 11
pretreated female subjects, 3.7 to 11.0 years of age. Study 2
enrolled 36 subjects (33 females and 3 males), 4.5 to 11.6 years of
age. Sixteen of these subjects were pretreated and 20 were
treatment-naïve. Endpoints were similar in both trials and included
measurements of the suppression of gonadotropins (luteinizing
hormone and follicle stimulating hormone) and gonadal sex steroids
(estrogen in girls and testosterone in boys, respectively).
Additional assessments were clinical (evidence of stabilization or
regression of signs of puberty) or gonadal steroid-dependent (bone
age, linear growth). In study 2 the primary measure of efficacy was
LH suppression (defined as a peak LH <4 mIU/mL following
stimulation with the GnRH analog leuprolide acetate). In both
trials the endpoints were achieved. In study 2, suppression of LH
was induced in all treatment naïve subjects and maintained in all
pretreated subjects one month after implantation and continued
through month 12. Secondary efficacy assessments indicated
stabilization of disease. In addition, in study 2 estradiol
suppression was present in 100% of the females through month 9 and
97% at month 12. Testosterone suppression was maintained in the
three pre-treated males.
Side Effects
Adverse events associated with the use of Supprelin LA may include, but are not limited to, the following:
- Implant site reaction
- Keloid scar
- Scar
- Suture related complication
- Application site pain
- Post procedural pain
Mechanism of Action
Supprelin LA is a GnRH agonist and an inhibitor of gonadotropin secretion when given continuously. It delivers approximately 65 mcg histrelin acetate per day. Following an initial stimulatory phase, chronic, subcutaneous administration of histrelin acetate desensitizes responsiveness of the pituitary gonadotropin which, in turn causes a reduction in ovarian and testicular steroidogenesis. Administration of histrelin acetate results in an initial increase in circulating levels of LH and FSH, leading to a transient increase in concentration of gonadal steroids (testosterone and dihydrotestosterone in males, and estrone and estradiol in premenopausal females). However, continuous administration of histrelin acetate causes a reversible down-regulation of the GnRH receptors in the pituitary gland and desensitization of the pituitary gonadotropes. These inhibitory effects result in decreased levels of LH and FSH.
Literature References
Eugster EA, Clarke W, Kletter GB, Lee PA, Neely EK, Reiter EO, Saenger P, Shulman D, Silverman L, Flood L, Gray W, Tierney D. Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial. The Journal of clinical endocrinology and metabolism 2007 May;92(5):1697-704.
Hirsch HJ, Gillis D, Strich D, Chertin B, Farkas A, Lindenberg T, Gelber H, Spitz IM. The histrelin implant: a novel treatment for central precocious puberty. Pediatrics 2005 Dec;116(6):e798-802
Weise M, Flor A, Barnes KM, Cutler GB Jr, Baron J. Determinants of growth during gonadotropin-releasing hormone analog therapy for precocious puberty. The Journal of clinical endocrinology and metabolism 2004 Jan;89(1):103-7
Feuillan PP, Jones JV, Barnes K, Klein KO, Cutler GB Jr Follow-up of children and young adults after GnRH-agonist therapy or central precocious puberty. Journal of endocrinological investigation 2001 Oct;24(9):734-6.
Barradell LB, McTavish D Histrelin. A review of its pharmacological properties and therapeutic role in central precocious puberty. Drugs 1993 Apr;45(4):570-88.
Additional Information
For additional information regarding Supprelin LA or central precocious puberty, please visit the Supprelin LA web page.
The FDA drug information shown here is licensed from Thomson CenterWatch. The information provided here is for general educational purposes only and does not constitute medical or pharmaceutical advice which should be sought from qualified medical and pharmaceutical advisers.
