Full Prescribing Information|Medication Guide

IN A PHASE 3 CLINICAL TRIAL:

Continuous LH suppression at Month 1 through Month 121

  • 100% of patients (n=36) achieved LH suppression at 1 month
  • 100% of patients maintained LH suppression after Month 1 through Month 12
LH Data 12 months

STUDY DESIGN: A Phase 3, prospective, multicenter, open-label study was conducted in 36 children (33 females and 3 males), 4.5 to 11.6 years of age, to evaluate the efficacy and safety of a 50-mg histrelin subcutaneous implant for the treatment of CPP in treatment-naïve (n=20) and pretreated (n=16) children. Baseline patient characteristics were typical of patients with CPP. Efficacy assessments included endpoints that measured the suppression of gonadotropins (LH and FSH) and gonadal sex steroids (estrogen in girls and testosterone in boys) on treatment. Other assessments were clinical (evidence of stabilization or regression of signs of puberty) or gonadal steroid-dependent (bone age advancement, linear growth). The primary measure of efficacy was LH suppression. The initial duration of therapy was 12 months (plus a 1-month follow-up period). At the 12-month visit, all patients had their initial implant from Day 1 removed and those patients who continued to meet all efficacy and safety parameters (as determined by the investigators) were eligible to receive a new 50-mg histrelin subcutaneous implant, with the possibility of rolling over into multiple 12-month extension phases.1,2

CPP=central precocious puberty.
FSH=follicle-stimulating hormone.
LH=luteinizing hormone.

In the Phase 3 Clinical Trial Extension:

Sustained LH suppression through 6 years3

  • No patient had a mean peak stimulated LH >2.3 mIU/mL
LH Data 72 months

STUDY DESIGN: A long-term extension of a Phase 3, prospective, open-label study evaluating the efficacy and safety of a 50-mg histrelin subcutaneous implant in children with CPP.2 Thirty-one patients deemed clinically appropriate for continued treatment were eligible to enter the study extension; the previous implant was removed after 12 months and a new implant inserted annually for up to 72 months, until the patient no longer required hormone suppression or the patient discontinued from the study. The primary endpoint was LH suppression as measured in response to gonadotropin releasing hormone analog (GnRHa) stimulation. Efficacy assessments also included secondary endpoints that measured the suppression of FSH and gonadal sex steroids (estrogen in girls and testosterone in boys) on treatment. Other assessments were clinical (evidence of stabilization or regression of signs of puberty) or gonadal steroid-dependent (bone age advancement, linear growth).3

CPP=central precocious puberty.
FSH=follicle-stimulating hormone.
GnRHa=gonadotropin-releasing hormone agonist.
LH=luteinizing hormone.

  • 31 out of 32 (97%) patients from the one-year study who were eligible continued in the long-term extension trial and received a new implant annually, as appropriate2
  • 13 patients received a total of 4 implants (4th implant inserted from Months 37-48), 11 received a 5th implant (Months 49-60), and 2 received a 6th implant (Months 61-72); 8 patients received posttreatment, long-term follow-up3
  • Mean peak stimulated serum LH levels for all patients remained suppressed throughout the study and were below the predetermined pubertal response for peak LH of 4 mIU/mL3
  • By 6 months of SUPPRELIN® LA implant removal, mean peak stimulated LH levels increased to pubertal levels in both GnRHa treatment-experienced and GnRHa treatment-naïve patients3

Discontinuation of SUPPRELIN® LA should be considered at the discretion of the physician and at the appropriate time point for the onset of puberty (approximately 11 years for females and 12 years for males).1

View data on secondary efficacy hormone assessment – gonadal suppression
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IMPORTANT SAFETY
INFORMATION ABOUT SUPPRELIN® LA

  • SUPPRELIN® LA is contraindicated in patients who are hypersensitive to gonadotropin releasing hormone (GnRH) or GnRH agonist analogs and in females who are or may become pregnant while receiving the drug. SUPPRELIN® LA may cause fetal harm or spontaneous abortion when administered to pregnant patients. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

  • SUPPRELIN® LA, like other GnRH agonists, initially causes a transient increase in serum concentrations of estradiol in females and testosterone in both sexes during the first week of treatment, with worsening of symptoms or onset of new symptoms during this period. Within 4 weeks of therapy, gonadal steroid suppression occurs and manifestations of puberty decrease.

  • Implant insertion and removal is a surgical procedure and should utilize aseptic technique. Careful adherence to the recommended insertion and removal procedures is recommended to avoid potential complications. Proper surgical technique is critical in minimizing adverse events related to the insertion and the removal of the histrelin implant. On occasion, localizing and/or removal of implant products have been difficult and imaging techniques were used including ultrasound, CT, or MRI (this implant is not radiopaque). In some cases, the implant broke during removal and multiple pieces were recovered. Confirm that the entire implant has been removed. Monitor luteinizing hormone, follicle stimulating hormone or testosterone for suppression of CPP. Rare events of spontaneous extrusion have been observed in clinical trials. During SUPPRELIN® LA treatment, patients should be evaluated for evidence of clinical and biochemical suppression of CPP manifestation.

  • Psychiatric events have been reported in patients taking GnRH agonists, including SUPPRELIN® LA. Postmarketing reports with this class of drugs include symptoms of emotional lability, such as crying, irritability, impatience, anger, and aggression. Depression, including rare reports of suicidal ideation and attempt, has been reported for GnRH agonists, including SUPPRELIN® LA, in children treated for central precocious puberty. Many, but not all, of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression. Monitor for development or worsening of psychiatric symptoms during treatment with SUPPRELIN® LA.

  • Postmarketing reports of convulsions have been observed in patients receiving GnRH agonists, including SUPPRELIN® LA. Reports with GnRH agonists have included patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and patients on concomitant medications that have been associated with convulsions such as bupropion and SSRIs. Convulsions have also been reported in patients in the absence of any of the conditions mentioned above.

  • Pseudotumor cerebri (idiopathic intracranial hypertension) have been reported in pediatric patients receiving GnRH agonists. Monitor patients for signs and symptoms of pseudotumor cerebri, including headache, papilledema, blurred vision, diplopia, loss of vision, pain behind the eye or pain with eye movement, tinnitus, dizziness, and nausea.

  • LH, FSH and estradiol or testosterone should be monitored at 1 month post implantation, then every 6 months. Every 6-12 months, height and bone age should be assessed.

  • In clinical trials, the most common adverse reactions involved the implant site and included discomfort, bruising, soreness, pain, tingling, itching, erythema, and implant area protrusion and swelling.

  • The safety and effectiveness in pediatric patients under the age of 2 years have not been established. The use of SUPPRELIN® LA in children under 2 years is not recommended.

INDICATION

  • SUPPRELIN® LA (histrelin acetate) subcutaneous implant is indicated for the treatment of children with central precocious puberty (CPP).

  • Children with CPP (neurogenic or idiopathic) have an early onset of secondary sexual characteristics (earlier than 8 years of age in females and 9 years of age in males). They also show a significantly advanced bone age that can result in diminished adult height attainment.

  • Prior to initiation of treatment, a clinical diagnosis of CPP should be confirmed by measurement of blood concentrations of total sex steroids, luteinizing hormone (LH) and follicle stimulating hormone (FSH) following stimulation with a GnRH analog, and assessment of bone age versus chronological age. Baseline evaluations should include height and weight measurements, diagnostic imaging of the brain (to rule out intracranial tumor), pelvic/testicular/adrenal ultrasound (to rule out steroid secreting tumors), human chorionic gonadotropin levels (to rule out a chorionic gonadotropin secreting tumor), and adrenal steroids to exclude congenital adrenal hyperplasia.

Please see the full Prescribing Information.

See More
IMPORTANT SAFETY
INFORMATION ABOUT SUPPRELIN® LA

  • SUPPRELIN® LA is contraindicated in patients who are hypersensitive to gonadotropin releasing hormone (GnRH) or GnRH agonist analogs and in females who are or may become pregnant while receiving the drug. SUPPRELIN® LA may cause fetal harm or spontaneous abortion when administered to pregnant patients. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

  • SUPPRELIN® LA, like other GnRH agonists, initially causes a transient increase in serum concentrations of estradiol in females and testosterone in both sexes during the first week of treatment, with worsening of symptoms or onset of new symptoms during this period. Within 4 weeks of therapy, gonadal steroid suppression occurs and manifestations of puberty decrease.

  • Implant insertion and removal is a surgical procedure and should utilize aseptic technique. Careful adherence to the recommended insertion and removal procedures is recommended to avoid potential complications. Proper surgical technique is critical in minimizing adverse events related to the insertion and the removal of the histrelin implant. On occasion, localizing and/or removal of implant products have been difficult and imaging techniques were used including ultrasound, CT, or MRI (this implant is not radiopaque). In some cases, the implant broke during removal and multiple pieces were recovered. Confirm that the entire implant has been removed. Monitor luteinizing hormone, follicle stimulating hormone or testosterone for suppression of CPP. Rare events of spontaneous extrusion have been observed in clinical trials. During SUPPRELIN® LA treatment, patients should be evaluated for evidence of clinical and biochemical suppression of CPP manifestation.

  • Psychiatric events have been reported in patients taking GnRH agonists, including SUPPRELIN® LA. Postmarketing reports with this class of drugs include symptoms of emotional lability, such as crying, irritability, impatience, anger, and aggression. Depression, including rare reports of suicidal ideation and attempt, has been reported for GnRH agonists, including SUPPRELIN® LA, in children treated for central precocious puberty. Many, but not all, of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression. Monitor for development or worsening of psychiatric symptoms during treatment with SUPPRELIN® LA.

  • Postmarketing reports of convulsions have been observed in patients receiving GnRH agonists, including SUPPRELIN® LA. Reports with GnRH agonists have included patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and patients on concomitant medications that have been associated with convulsions such as bupropion and SSRIs. Convulsions have also been reported in patients in the absence of any of the conditions mentioned above.

  • Pseudotumor cerebri (idiopathic intracranial hypertension) have been reported in pediatric patients receiving GnRH agonists. Monitor patients for signs and symptoms of pseudotumor cerebri, including headache, papilledema, blurred vision, diplopia, loss of vision, pain behind the eye or pain with eye movement, tinnitus, dizziness, and nausea.

  • LH, FSH and estradiol or testosterone should be monitored at 1 month post implantation, then every 6 months. Every 6-12 months, height and bone age should be assessed.

  • In clinical trials, the most common adverse reactions involved the implant site and included discomfort, bruising, soreness, pain, tingling, itching, erythema, and implant area protrusion and swelling.

  • The safety and effectiveness in pediatric patients under the age of 2 years have not been established. The use of SUPPRELIN® LA in children under 2 years is not recommended.

INDICATION

  • SUPPRELIN® LA (histrelin acetate) subcutaneous implant is indicated for the treatment of children with central precocious puberty (CPP).

  • Children with CPP (neurogenic or idiopathic) have an early onset of secondary sexual characteristics (earlier than 8 years of age in females and 9 years of age in males). They also show a significantly advanced bone age that can result in diminished adult height attainment.

  • Prior to initiation of treatment, a clinical diagnosis of CPP should be confirmed by measurement of blood concentrations of total sex steroids, luteinizing hormone (LH) and follicle stimulating hormone (FSH) following stimulation with a GnRH analog, and assessment of bone age versus chronological age. Baseline evaluations should include height and weight measurements, diagnostic imaging of the brain (to rule out intracranial tumor), pelvic/testicular/adrenal ultrasound (to rule out steroid secreting tumors), human chorionic gonadotropin levels (to rule out a chorionic gonadotropin secreting tumor), and adrenal steroids to exclude congenital adrenal hyperplasia.

Please see the full Prescribing Information.

References: 1. SUPPRELIN® LA [package insert]. Endo USA, Inc. 2. Eugster EA, Clarke W, Kletter GB, et al. Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial. J Clin Endocrinol Metab. 2007;92(5):1697-1704. 3. Silverman LA, Neely EK, Kletter GB, et al. Long-term continuous suppression with once-yearly histrelin subcutaneous implants for the treatment of central precocious puberty: a final report of a phase 3 multicenter trial. J Clin Endocrinol Metab. 2015;100(6):2354-2363.

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