Supprelin

Histrelin acetate · Implant · Subcutaneous

Prescription (Rx) Gonadotropin Releasing Hormone Receptor Agonist

Uses

(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. SUPPRELIN LA is a gonadotropin releasing hormone (GnRH) agonist indicated for the treatment of children with central precocious puberty (CPP) ( 1 ).

Dosage and administration

The recommended dose of SUPPRELIN LA is one implant every 12 months. The implant is inserted subcutaneously in the inner aspect of the upper arm and provides continuous release of histrelin for 12 months of hormonal therapy ( 2 ). 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 acetate (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). 2.2 Recommended Procedure for Implant Insertion and Removal This procedure section is intended to provide guidance for the insertion and removal of SUPPRELIN LA. The actual procedure used, however, is at the discretion of the qualified healthcare provider performing the procedure. Insertion of a new implant can proceed using the following Suggested Insertion Procedure . If a previous SUPPRELIN LA implant must first be removed, please see the Suggested Removal Procedure instructions below. Suggested Insertion Procedure The supplies necessary to insert the implant, including the Insertion Tool and local anesthetic, are provided in a separate Implantation Kit that is shipped along with the implant. Please note that the implant should be kept refrigerated (2-8°C) in its sealed vial, pouch, and carton, until needed for the procedure. Once removed from refrigeration, the vial containing the implant (still in its unopened pouch and carton) may remain at room temperature for up to 7 days, if necessary, before being used. If not used in that time, the packaged implant may again be properly refrigerated until the expiration date on the carton. NOTE: The Implantation Kit is to be stored at room temperature and should not be refrigerated. Insertion of the SUPPRELIN LA implant is a surgical procedure. Sterile gloves and aseptic technique must be used to minimize any chance of infection. Setting up the Sterile Field Using proper aseptic technique, the sterilized components of the Implantation Kit needed for the insertion procedure, including the Insertion Tool, are to be carefully dispensed from their packaging onto the Sterile Field drape ( non -fenestrated) provided. NOTE THAT THE KIT BOX AND ALL PACKAGING ARE NOT STERILE and should be kept off of the Sterile Field drape. DO NOT PLACE THE VIAL OF LOCAL ANESTHETIC OR THE VIAL CONTAINING THE IMPLANT ONTO THE DRAPE as the exterior surface of these vials is not sterile. The implant vial should not be opened until just before the time of insertion. Open the vial by removing the metal band and carefully pour the sterile contents (implant and sterile saline) onto the Sterile Field drape. The implant can then be handled with sterile gloves or with the sterile mosquito clamp provided. AVOID bending or pinching the implant . Preparing the Patient and the Insertion Site The patient should be on his/her back, ideally with the arm least used (e.g., left arm for a right-handed person) positioned, either bent or extended, so that the physician has ready access to the inner aspect of the upper arm. Propping the arm with pillows may help the patient more easily hold the position. The suggested optimum site for subcutaneous insertion is approximately half-way between the shoulder and the elbow, in line with the crease between the biceps and triceps muscles. Antiseptic Swab the insertion area with topical antiseptic, then overlay with the fenestrated Sterile Field drape provided, so that the opening is over the insertion site (for clarity of illustration, the following images do not show the drape). Anesthetic The method of anesthesia utilized (i.e., local, conscious sedation, general) is at the discretion of the healthcare provider. If local anesthesia is selected: a vial of sterile local anesthetic (note that the exterior of the vial is not sterile ) has been provided along with a sterile hypodermic needle for injection. After determining the absence of known allergies to the anesthetic agent, inject anesthetic into the subcutaneous tissue, starting at the planned incision site, then infiltrating along the intended subcutaneous insertion path, up to the length of the implant (a little more than one inch). Local anesthesia may also be supplemented by the use of distraction techniques. The following sections describe the suggested procedure for insertion of the implant using the Insertion Tool provided. The method of insertion used, however, is at the discretion of the healthcare provider performing the procedure. Loading the Insertion Tool The sterile Insertion Tool is comprised of a fixed handle attached to a retractable, bevel-tipped cannula, into the chamber of which the implant is to be placed for subcutaneous insertion. The cannula can be extended and retracted. The fully extended cannula contains a fixed piston upon which the implant, once inserted, rests. During the final step of the insertion procedure, the cannula will be retracted into the handle using the slide mechanism (green button), thereby exposing and leaving the implant to remain in the subcutaneous tissue. When first grasping the sterile Insertion Tool, confirm that the cannula is fully extended. Verify this by inspecting the position of the green retraction button. The button should be locked in position all the way forward, towards the cannula, farthest from the handle. The implant can be picked up using sterile gloves or with the sterile mosquito clamp provided.

Dosage forms and strengths

3 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. SUPPRELIN LA is available as a 50 mg histrelin acetate subcutaneous implant which delivers approximately 65 mcg histrelin acetate per day over 12 months ( 3 ).

Contraindications

4 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 )] . History of hypersensitivity to gonadotropin releasing hormone (GnRH) or GnRH analogs ( 4 ). Pregnancy ( 4 ).

Warnings and precautions

Initial Agnostic Action: Initial transient increases of estradiol and/or testosterone may cause a temporary worsening of symptoms ( 5.1 ). Implant Breakage: Have been observed during implant removal. Monitor luteinizing hormone, follicle stimulating hormone or testosterone for suppression of CPP ( 5.2 , 5.6 ) Psychiatric Events: Have been reported in patients taking GnRH agonists. Events include emotional lability, such as crying, irritability, impatience, anger, and aggression. Monitor for development or worsening of psychiatric symptoms. ( 5.3 ) Convulsions: Have been observed in patients receiving GnRH agonists with or without a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and in patients on concomitant medications that have been associated with convulsions. ( 5.4 ) Severe Cutaneous Adverse Reactions: Have been reported in patients receiving GnRH agonists. Interrupt SUPPRELIN LA if signs or symptoms of severe cutaneous adverse reactions develop. Permanently discontinue SUPPRELIN LA if a severe cutaneous adverse reaction is confirmed. ( 5.5 ) Pseudotumor Cerebri (Idiopathic Intracranial Hypertension): Have been reported in pediatric patients receiving GnRH agonists. Monitor patients for headache, papilledema, and blurred vision. ( 5.6 ) 5.1 Initial Agonistic Action 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. Patients may experience worsening of symptoms or onset of new symptoms during this period. However, within 4 weeks of histrelin therapy, suppression of gonadal steroids occurs and manifestations of puberty decrease. 5.2 Implant Breakage Implant insertion is a surgical procedure and it is important that the insertion instructions are followed to avoid potential complications. The insertion and removal of the implant should be done aseptically. 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 (note: the histrelin 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. If the implant was not retrieved completely, the remaining pieces should be removed following the instructions in the Suggested Removal Procedure section [see Dosage and Administration ( 2.2 )]. Rare events of spontaneous extrusion of the implant have been observed in clinical trials. During SUPPRELIN LA treatment, patients should be evaluated for evidence of clinical and biochemical suppression of CPP manifestations (see Section 5.6 , Monitoring and Laboratory tests). Detailed instructions on the insertion and removal procedures of the implant are provided above [see Dosage and Administration ( 2.2 )] . 5.3 Psychiatric Events 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. Monitor for development or worsening of psychiatric symptoms during treatment with SUPPRELIN LA [see Adverse Reactions ( 6 )] . 5.4 Convulsions 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. 5.5 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions have been reported in patients receiving GnRH agonists [see Adverse Reactions ( 6.3 )] . These reactions include Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), including cases with visceral involvement and/or requiring skin grafts. Monitor patients for signs and symptoms of severe cutaneous adverse reactions such as fever, flu-like symptoms, mucosal lesions, progressive skin rash or lymphadenopathy. Advise patients and caregivers of the signs and symptoms of severe cutaneous adverse reactions. If a severe cutaneous adverse reaction is suspected, interrupt SUPPRELIN LA. Consult a healthcare provider with expertise in the diagnosis and management of severe cutaneous adverse reactions. If a diagnosis of severe cutaneous adverse reaction is confirmed permanently discontinue SUPPRELIN LA. 5.6 Pseudotumor Cerebri (Idiopathic Intracranial Hypertension) 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. 5.7 Monitoring and Laboratory Tests LH, FSH and estradiol or testosterone should be monitored at 1 month post implantation then every 6 months thereafter. Additionally, height (for calculation of height velocity) and bone age should be assessed every 6-12 months.

Side effects

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 )] The most common adverse reaction is implant site reaction (51.1%), including complications related to the insertion or removal of the implant ( 6 ). Adverse events related to suppression of endogenous sex steroid secretion may occur ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Endo at 1-800-462-3636 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Overall Adverse Reaction Profile The most common adverse reactions with SUPPRELIN LA involved the implant site. Local reactions after implant insertion include bruising, pain, soreness, erythema and swelling. During the early phase of therapy, gonadotropins and sex steroids rise above baseline because of the natural stimulatory effect of the drug. Therefore, an increase in clinical signs and symptoms may be observed [see Warnings and Precautions ( 5.1 )] . 6.2 Adverse Reactions in Clinical Trials Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of SUPPRELIN LA in children with CPP was evaluated in two single-arm clinical trials conducted in a total of 47 patients (44 females and 3 males) over a period of time ranging from 9 to 18 months. The most commonly reported adverse reaction was implant site reaction, which was reported by 24 of 47 (51.1%) patients. Implant site reaction includes discomfort, bruising, soreness, pain, tingling, itching, implant area protrusion and swelling. Two subjects experienced a serious adverse reaction: 1 subject who coincidentally had Stargardt’s Disease experienced amblyopia and 1 subject had a benign pituitary tumor (pituitary adenoma). One subject discontinued the study due to an adverse reaction of infection at the implant site. There were no clinically meaningful findings in standard clinical hematology and chemistry tests and/or in vital signs. The incidence of implantation adverse events reported by more than 2 patients are summarized in Table 1. Table 1: Incidence of implantation adverse reactions reported by ≥ 2 patients treated with SUPPRELIN LA in both clinical trials Adverse Reactions N=47 N (%) Implant site reaction 24 (51.1) Keloid scar 3 (6.4) Scar 3 (6.4) Suture related complication 3 (6.4) Application site pain 2 (4.3) Post procedural pain 2 (4.3) The following adverse reactions were reported as possibly related or related in 1 patient each: wound infection, breast tenderness, dysmenorrhea, epistaxis, erythema, feeling cold, gynecomastia, headache, menorrhagia, migraine, mood swings, pituitary tumor benign, pruritus, weight increased, disease progression and influenza-like illness. The adverse reaction metrorrhagia was reported as possibly related or related in 2 patients. 6.3 Post-marketing Experience The following adverse reactions have been identified during post approval use of SUPPRELIN LA or GnRH agonists. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. General Disorders and Administration Site Conditions : implant breakage Psychiatric Disorders : Emotional lability, such as crying, irritability, impatience, anger, and aggression. Depression, including rare reports of suicidal ideation and attempt. Many, but not all, of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression. Nervous System Disorders : seizures. Pseudotumor cerebri (idiopathic intracranial hypertension) have been observed with GnRH agonists. Skin Reactions: erythema multiforme, bullous dermatitis, dermatitis exfoliative, drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome and toxic epidermal necrolysis, and acute generalized exanthematous pustulosis.

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).

Use in specific populations

Use of SUPPRELIN LA in children less than 2 years of age is not recommended ( 8.4 ). 8.1 Pregnancy Risk Summary SUPPRELIN LA is contraindicated during pregnancy [see Contraindications ( 4 )] since expected hormonal changes that occur with SUPPRELIN LA treatment increase the risk for pregnancy loss. The limited data with histrelin use in pregnant women are insufficient to determine a drug-associated risk for major birth defects or adverse developmental outcomes. Consistent with mechanism of action for SUPPRELIN LA [see Clinical Pharmacology ( 12.1 )], animal reproduction studies showed an increase in fetal loss at clinically relevant exposures. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Histrelin acetate administered to pregnant rats during the period of organogenesis increased fetal mortality and post-implantation loss at doses of 1, 3, 5 or 15 mcg/kg/day, approximating clinical exposure based on body surface area. These dosages also reduced maternal body weight gain, stimulated ovarian follicular development, increased placental weight and caused abnormal morphology and an increase in fetal size. Histrelin acetate administered to pregnant rabbits during the period of organogenesis increased fetal mortality and abortion/early termination at the two highest doses and caused total litter loss at all doses of 20, 50 or 80 mcg/kg/day (approximately 3- to 12-times clinical exposures based on body surface area). 8.2 Lactation Risk Summary There are no data on the presence of SUPPRELIN LA in human or animal milk, the effects on the breastfed infant, or the effects on milk production. Absorption and systemic activity are not expected from potential exposure to the peptide, histrelin, in the breast milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SUPPRELIN LA and any potential adverse effects on the breastfed child from SUPPRELIN LA or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients below the age of 2 years have not been established. The use of SUPPRELIN LA in children under 2 years is not recommended.

Pregnancy

8.1 Pregnancy Risk Summary SUPPRELIN LA is contraindicated during pregnancy [see Contraindications ( 4 )] since expected hormonal changes that occur with SUPPRELIN LA treatment increase the risk for pregnancy loss. The limited data with histrelin use in pregnant women are insufficient to determine a drug-associated risk for major birth defects or adverse developmental outcomes. Consistent with mechanism of action for SUPPRELIN LA [see Clinical Pharmacology ( 12.1 )], animal reproduction studies showed an increase in fetal loss at clinically relevant exposures. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Histrelin acetate administered to pregnant rats during the period of organogenesis increased fetal mortality and post-implantation loss at doses of 1, 3, 5 or 15 mcg/kg/day, approximating clinical exposure based on body surface area. These dosages also reduced maternal body weight gain, stimulated ovarian follicular development, increased placental weight and caused abnormal morphology and an increase in fetal size. Histrelin acetate administered to pregnant rabbits during the period of organogenesis increased fetal mortality and abortion/early termination at the two highest doses and caused total litter loss at all doses of 20, 50 or 80 mcg/kg/day (approximately 3- to 12-times clinical exposures based on body surface area).

Pediatric use

8.4 Pediatric Use Safety and effectiveness in pediatric patients below the age of 2 years have not been established. The use of SUPPRELIN LA in children under 2 years is not recommended.

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.

Description

11 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. Figure 1: SUPPRELIN LA Implant Diagram (not to scale) 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 C 66 H 86 N 18 O 12 x 2 CH 3 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) is represented below in Figure 2. Figure 2: Structure of 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 ) ]. hydrogel figure Chemical Structure

Mechanism of action

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. 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.

How supplied

67979-002-01) is supplied in a corrugated shipping carton that contains 2 inner cartons: a small one for the vial containing the SUPPRELIN LA implant, which is shipped with a cold pack inside a polystyrene cooler that must be refrigerated upon arrival, and a larger one comprising the Implantation Kit, which must not be refrigerated, for use during insertion or removal of SUPPRELIN LA. The SUPPRELIN LA implant contains 50 mg of histrelin acetate. The SUPPRELIN LA implant carton contains a cold pack for refrigerated shipment and a small carton containing an amber plastic pouch. Inside the pouch is a glass vial with a Teflon-coated stopper and an aluminum seal, containing the implant in 2 mL of sterile 1.8% sodium chloride solution. ( Note : The 3.5 mL vial is not completely filled with saline). Upon receipt, refrigerate the small carton containing the amber plastic pouch and glass vial (with the implant inside) until the day of insertion. The implant vial should not be opened until just before the time of insertion. SUPPRELIN LA is stable when stored refrigerated, in its sealed vial, pouch, and carton, at 2-8°C (36-46°F) until the expiration date provided. Excursion permitted to 25°C (77°F) for 7 days. Do not freeze. Protect from light.

Patient information

Advise the patient to read the FDA-Approved patient labeling ( Medication Guide ). Initial Agonistic Action Patients should be advised that a transient worsening of symptoms of puberty or onset of new symptoms may occur initially. However, within 4 weeks of histrelin therapy, complete suppression of gonadal steroids occurs and manifestations of puberty decrease [ see Warnings and Precautions ( 5.1 )]. Post-insertion Care Patients should be instructed to refrain from getting the inserted arm wet for 24 hours and from strenuous exertion of the inserted arm for 7 days after implant insertion to allow the incision to fully close. The adhesive elastic bandage can be removed at that time. The patient should not remove the surgical strips; rather, the strips should be allowed to fall off on their own after several days. Psychiatric Adverse Events Inform caregivers that symptoms of emotional lability, such as crying, irritability, impatience, anger, and aggression, have been observed in patients receiving GnRH agonists, including SUPPRELIN LA. Alert caregivers to the possibility of development or worsening of psychiatric symptoms, including depression, during treatment with SUPPRELIN LA [ see Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6.3 ) ]. Convulsions Inform caregivers that reports of convulsions have been observed in patients receiving GnRH agonists, including SUPPRELIN LA. 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 may be at risk [ see Warnings and Precautions ( 5.4 ) ]. Severe Cutaneous Adverse Reactions Inform patients and/or caregivers that severe cutaneous adverse reactions may occur during treatment with SUPPRELIN LA. Advise patients and/or caregivers to stop SUPPRELIN LA and immediately contact their healthcare provider if they experience signs or symptoms of severe cutaneous adverse reactions [see Warnings and Precautions ( 5.5 )] . Pseudotumor Cerebri (Idiopathic Intracranial Hypertension) Inform patients and caregivers that reports of pseudotumor cerebri (idiopathic intracranial hypertension) have been observed in pediatric patients receiving GnRH agonists. Advise patients and caregivers to monitor for headache, and vision issues such as blurred vision, double vision, loss of vision, pain behind the eye or pain with eye movement, ringing in the ears, dizziness, and nausea. Advise patients and caregivers to contact their healthcare provider if the patient develops any of these symptoms. [ see Warnings and Precautions ( 5.6 ) ]. Common Adverse Reactions Patients should be advised to report to their physician any severe pain, redness, or swelling in and around the implant site. Infrequently, SUPPRELIN LA may be expelled from the body through the original incision site, rarely without the patient noticing. The patient should be instructed to monitor the incision site until it is healed. The patient should also return for routine checks of their condition and to ensure that SUPPRELIN LA is present and functioning in his/her body [ see Adverse Reactions ( 6.1 ) ]. For more information, call 1-800-462-3636 or visit www.supprelinla.com . Manufactured for: Endo USA Malvern, PA 19355 © 2025 Endo, Inc. or one of its affiliates. Revised: 09/2025

Label text from the FDA structured product label by Endo USA, Inc. (revised Sep 25, 2025). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Histrelin Acetate in 1 product

Supprelin NDC products (1)

NDC	Strength & form	Labeler	Type
67979-002	Histrelin Acetate 50 mg/1 Implant	Endo USA, Inc.	NDA

Frequently asked questions

What is Supprelin used for?

What are the side effects of Supprelin?

Who makes Supprelin?

Supprelin is listed by 1 labeler in the FDA NDC directory, including Endo USA, Inc..