SUPPRELIN LA- histrelin acetate implant
Endo Pharmaceuticals Solutions Inc.
1 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.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dose
The recommended dose of SUPPRELIN LA is one implant every 12 months. Each implant contains 50 mg histrelin acetate. The implant is inserted subcutaneously in the inner aspect of the upper arm and provides continuous release of histrelin (65 mcg/day) for 12 months of hormonal therapy. SUPPRELIN LA should be removed after 12 months of therapy (the implant has been designed to allow for a few additional weeks of histrelin acetate release, in order to allow flexibility of medical appointments). At the time an implant is removed, another implant may be inserted to continue therapy. 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).
DOSAGE FORMS AND STRENGTHS
SUPPRELIN LA is a sterile, nonbiodegradable, diffusion-controlled, hydrogel polymer reservoir drug delivery system designed to deliver histrelin acetate continuously for 12 months after subcutaneous implantation. The sterile implant contains 50 mg histrelin acetate and delivers approximately 65 mcg histrelin acetate per day over 12 months.
4 CONTRAINDICATIONS
SUPPRELIN LA is contraindicated in patients who are hypersensitive to gonadotropin releasing hormone (GnRH) or GnRH agonist analogs.
SUPPRELIN LA is contraindicated in females who are or may become pregnant while receiving the drug. SUPPRELIN LA may cause fetal harm 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. The possibility exists that spontaneous abortion may occur [see Use in Specific Populations (8.1) ].
DESCRIPTION
SUPPRELIN LA is a sterile, non-biodegradable, diffusion-controlled, hydrogel polymer reservoir containing histrelin acetate, a synthetic nonapeptide analog of the naturally occurring gonadotropin releasing hormone (GnRH) possessing a greater potency than the natural sequence hormone. SUPPRELIN LA is designed to deliver approximately 65 mcg histrelin acetate per day over 12 months.
The SUPPRELIN LA implant looks like a small thin flexible tube and consists of a 50-mg histrelin acetate drug core inside a 3.5 cm by 3 mm, cylindrical, hydrogel polymer reservoir (Figure 1). The implant may appear partially to completely full with variation in color from off-white to light brown. The color may be uneven within the core.
The chemical name of histrelin acetate is: L-Pyroglutamyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-N-benzyl-D-histidyl-L-leucyl-L-arginyl-L-proline N-ethylamide, acetate salt.
The molecular formula for histrelin acetate is C66 H86 N18 O12 x 2 CH3 COOH and its molecular weight is 1443.70 (or 1323.52 as free base). Histrelin is also chemically described as 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-Nt-benzyl-D-histidyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide diacetate. The chemical structure of the free base (histrelin)
The drug core also contains the inactive ingredient stearic acid NF. The hydrogel polymer reservoir is a hydrophilic cartridge composed of 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, trimethylolpropane trimethacrylate, benzoin methyl ether, Perkadox-16, and Triton X-100. Each implant is packaged hydrated in a glass vial containing 2 mL of sterile 1.8% sodium chloride solution, so that it is primed for immediate release of the drug upon insertion.
A single use, sterile, Insertion Tool is provided along with the implant that can be used for the placement of the SUPPRELIN LA implant into the subcutaneous tissue of the inner aspect of the upper arm. The Insertion Tool is enclosed in a sterile bag and is provided separately from the implant in the Implantation Kit [see Recommended Procedure for Implant Insertion and Removal (2.2) ].
12 CLINICAL PHARMACOLOGY
12.1 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.
SUPPRELIN� LA [Suh-Preh-Lin El-Ay]
(histrelin acetate) subcutaneous implant
Read the Patient Information that comes with SUPPRELIN LA before your child begins treatment. This information does not take the place of talking with your child's doctor about their medical condition or treatment.
What is SUPPRELIN LA?
SUPPRELIN LA is an under-the-skin (subcutaneous) implant that contains the medicine histrelin, a gonadotropin releasing hormone (GnRH). SUPPRELIN LA is used for treatment of children with central precocious puberty (CPP).
CPP makes puberty come early in girls (before 8 years of age) and in boys (before 9 years of age). Signs of early puberty include breast enlargement in girls and the appearance of hair in the genital area in boys and girls. SUPPRELIN LA works by reducing the amount of sex hormones in the blood to delay early puberty.
Who should not use SUPPRELIN LA?
Your child should not use SUPPRELIN LA if he/she is allergic to gonadotropin releasing hormone (GnRH), GnRH agonist medicines, or anything in the SUPPRELIN LA implant. SUPPRELIN LA should not be used in:
children under 2 years of age
women who are or may become pregnant (SUPPRELIN LA can cause birth defects or loss of the baby).
How is SUPPRELIN LA used?
Your child's doctor should do tests to make sure your child has CPP before treating your child with SUPPRELIN LA.
SUPPRELIN LA lasts for 12 months. One implant provides the medicine for 12 months. After 12 months, SUPPRELIN LA must be removed. The doctor may insert a new SUPPRELIN LA at this time to continue treatment.
SUPPRELIN LA is placed under the skin of the inside of the upper arm. The doctor will temporarily numb the arm of your child, make a small cut, and then place SUPPRELIN LA under the skin. The cut may be closed with stitches or surgical strips and covered with a pressure bandage.
Your child should keep the arm clean and dry and should not swim or bathe for 24 hours. The bandage can be removed after 24 hours. Do not remove any surgical strips. They will fall off on their own in several days.
Your child should avoid heavy play or exercise that uses the implanted arm for 7 days. After the cut has healed, your child can go back to his or her normal activities. The doctor will give you complete instructions.
Keep all scheduled visits to the doctor. Your child's doctor will do regular exams and blood tests to check for signs of puberty. Sometimes the doctor will have to do special examinations, such as ultrasound or MRI, if the SUPPRELIN LA implant is difficult to find under your child's skin.
What are the possible side effects of SUPPRELIN LA?
In the first few weeks of treatment, SUPPRELIN LA can cause a brief increase in some hormones, and during this time you may notice more signs of puberty in your child, including light vaginal bleeding and breast enlargement in girls. Within 4 weeks of treatment, you should see signs in your child that puberty is stopping.
The most common side effects of SUPPRELIN LA are skin reactions at the place where the implant is inserted. Such reactions may include bruising, soreness, pain, tingling, itching, and swelling. They usually go away without treatment within 2 weeks. Call your child's doctor if your child has bleeding, redness or pain at the insertion site.
Serious and life-threatening allergic reactions have happened with GnRH medicines (the type of medicine in SUPPRELIN LA).
These may not be all the side effects of SUPPRELIN LA. Ask your child's doctor for more information.
