Histrelin Acetate (3 brand names, 2 dosage forms, 2 routes)
Available dosage forms: INJECTABLE, IMPLANT.
Routes of administration: INJECTION, SUBCUTANEOUS.
Brand Names
- SUPPRELIN
- SUPPRELIN LA
- VANTAS
Indications and Usage
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.
Contraindications
SUPPRELIN LA is contraindicated in: Patients who are hypersensitive to gonadotropin releasing hormone (GnRH) or GnRH agonist analogs Pregnancy [see Use in Specific Populations (8.1)].
Adverse Reactions
The following serious adverse reactions are described here and elsewhere in the label: Initial Agonist Action [see Warnings and Precautions (5.1)] Implant Breakage [see Warnings and Precautions (5.2)] Psychiatric Events [see Warnings and Precautions (5.3)] Convulsions [see Warnings and Precautions (5.4)] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.5)] Pseudotumor Cerebri (Idiopathic Intracranial Hypertension) [see Warnings and Precautions (5.6)]
Drug Interactions
Overview: No formal drug-drug, drug-food, or drug-herb interaction studies were performed with SUPPRELIN LA. Drug-Laboratory Interactions: Therapy with SUPPRELIN LA results in suppression of the pituitary-gonadal system. Results of diagnostic tests of pituitary gonadotropic and gonadal functions conducted during and after SUPPRELIN LA therapy may be affected. SUPPRELIN LA decreased mean serum insulin like growth factor 1 (IGF 1) levels by approximately 11% in one study (Study 1). SUPPRELIN LA increased the serum concentration of dehydroepiandrosterone (DHEA) in 8 of 36 patients in another study (Study 2).
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. Both animal and human studies indicate that 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. In humans, 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.
Overdosage
There have been no reports of overdose in SUPPRELIN LA clinical trials. High doses of histrelin acetate injection in animal studies were generally associated only with effects attributed to the expected pharmacology. The method of drug delivery makes accidental or intentional overdosage unlikely.