Lupron Depot-PED

Warnings and Precautions, Severe Cutaneous Adverse Reactions ( 5.4 ) 9/2025

1 INDICATIONS AND USAGE LUPRON DEPOT-PED is indicated for the treatment of pediatric patients with central precocious puberty (CPP). LUPRON DEPOT-PED is a gonadotropin releasing hormone (GnRH) agonist indicated for the treatment of pediatric patients with central precocious puberty. ( 1 )

2 DOSAGE AND ADMINISTRATION Must be administered by a healthcare professional. ( 2.1 ) Select appropriate LUPRON DEPOT-PED syringe for the intended dosing frequency and administer intramuscularly. ( 2.1 ) For 1-month administration: Starting dose is 7.5, 11.25, or 15 mg based on the patient’s weight. ( 2.2 ) For 3-month administration: Doses are either 11.25 or 30 mg. ( 2.3 ) For 6-month administration: Dose is 45 mg. ( 2.4 ) Monitor hormonal and clinical parameters during treatment to ensure adequate suppression. ( 2.2 , 2.3 , 2.4 ) Rotate injection site periodically. ( 2.5 ) See Full Prescribing Information for administration and reconstitution instructions. ( 2.5 , 2.6 ) Figure 1 Figure 2 blue line syringe shake Figure 5 lupro loc click one 2.1 Important Dosing Information LUPRON DEPOT-PED must be administered by a healthcare professional. Individualize the dose of LUPRON DEPOT-PED for each patient. Select the appropriate LUPRON-DEPOT PED syringe for the intended dosing frequency and administer intramuscularly. Each LUPRON DEPOT-PED strength and formulation has different release characteristics. Do not use partial syringes or a combination of syringes to achieve a particular dose. In the case of inadequate suppression of pituitary gonadotropins and peripheral sex steroids with a maximal dosage, consider other available gonadotropin releasing hormone (GnRH) agonists indicated for the treatment of central precocious puberty. Discontinue LUPRON DEPOT-PED at the appropriate age of onset of puberty. 2.2 Dosage and Recommended Monitoring for 1-Month Administration Administer LUPRON DEPOT-PED 7.5 mg, 11.25 mg, or 15 mg for 1-month administration as a single-dose intramuscular injection once every month. The starting dose is based on the patient's weight (see Table 1). Table 1. Dos age Recommendations Based on Body Weight for LUPRON DEPOT-PED for 1- M onth A dministration Body Weight Once Monthly Recommended Dos ag e Less than or equal to 25 kg 7.5 mg Greater than 25 kg up to 37.5 kg 11.25 mg Greater than 37.5 kg 15 mg The dosage may need to be adjusted with changes in body weight. If adequate hormonal and clinical suppression is not achieved with the starting dose, increase the dosage to the next available higher dose (e.g., 11.25 mg or 15 mg at the next monthly injection). Monitor response with a GnRH stimulation test, basal luteinizing hormone (LH) or serum concentration of sex steroid levels beginning 1 to 2 months following initiation of therapy, with changing doses, or further as judged clinically appropriate in order to confirm maintenance of efficacy. Assess height (for calculation of growth rate) and bone age every 6 to 12 months. 2.3 Dosage and Recommended Monitoring for 3-Month Administration Use LUPRON DEPOT-PED 11.25 mg or 30 mg for 3-month administration once every three months (12 weeks) as a single-dose intramuscular injection. Monitor response with a GnRH stimulation test, basal LH or serum concentration of sex steroid levels at months 2 to 3, month 6 and further as judged clinically appropriate, to confirm maintenance of efficacy. Assess height (for calculation of growth rate) and bone age every 6 to 12 months. 2.4 Dosage and Recommended Monitoring for 6-Month Administration Use LUPRON DEPOT-PED 45 mg for 6-month administration once every six months (24 weeks) as a single-dose intramuscular injection. Monitor response with a GnRH stimulation test, basal LH or serum concentration of sex steroid levels at months 5 to 6 and further as judged clinically appropriate, to confirm maintenance of efficacy. Assess height (for calculation of growth rate) and bone age every 6 to 12 months. 2.5 Important Administration Instructions Administer LUPRON DEPOT-PED as a single-dose intramuscular injection into the gluteal area, anterior thigh, or shoulder. Rotate injection sites within the same region from one injection to the next. Inject immediately after reconstitution. Discard if not used within 2 hours. 2.6 Reconstitution Instr …

3 DOSAGE FORMS AND STRENGTHS For depot suspension: a white lyophilized powder supplied in a single-dose, prefilled dual-chamber syringe with a colorless diluent is available as: For 1-month administration: 7.5 mg, 11.25 mg, or 15 mg of leuprolide acetate For 3-month administration: 11.25 mg or 30 mg of leuprolide acetate For 6-month administration: 45 mg of leuprolide acetate For depot suspension: leuprolide acetate as a lyophilized powder supplied in single-dose, prefilled dual-chamber syringe with diluent ( 3 ): For 1-month administration: 7.5 mg, 11.25 mg, or 15 mg For 3-month administration: 11.25 mg or 30 mg For 6-month administration: 45 mg

4 CONTRAINDICATIONS Hypersensitivity to GnRH, GnRH agonists or any of the excipients in LUPRON DEPOT-PED. Anaphylactic reactions to synthetic GnRH or GnRH agonists have been reported [see Adverse Reactions ( 6.2 )] . Pregnancy: LUPRON DEPOT-PED may cause fetal harm [see Use in Specific Populations ( 8.1 )] . Hypersensitivity reactions to GnRH, GnRH agonists or any of the excipients in LUPRON DEPOT-PED ( 4 ) Pregnancy ( 4 , 8.1 )

6 ADVERSE REACTIONS The following serious adverse reactions are described here and elsewhere in the label: Initial rise in gonadotropin and sex steroid levels [see Warnings and Precautions ( 5.1 ) ] . Psychiatric Events [see Warnings and Precautions ( 5.2 ) ] . Convulsions [see Warnings and Precautions ( 5.3 ) ] . Severe Cutaneous Adverse Reactions (SCARs) [see Warnings and Precautions ( 5.4 )] Pseudotumor Cerebri (Idiopathic Intracranial Hypertension) [see Warnings and Precautions ( 5.5 ) ] Adverse events related to suppression of endogenous sex steroid secretion and injection site reactions including abscess may occur with LUPRON DEPOT-PED 7.5 mg, 11.25 mg, or 15 mg for 1-month administration. ( 6.1 , 6.2 ) In the clinical studies for LUPRON DEPOT-PED 7.5 mg, 11.25 mg, or 15mg for 1-month administration the most common (≥2%) adverse reactions were: emotional lability, headache, general pain, acne/seborrhea, rash including erythema multiforme and vaginitis/vaginal bleeding/vaginal discharge. ( 6.1 ) In the clinical studies for LUPRON DEPOT-PED 11.25 mg or 30 mg for 3-month administration the most common ( > 2%) adverse reactions were: injection site pain, weight increased, headache, mood altered, and injection site swelling. ( 6.1 ) In the clinical study for LUPRON DEPOT-PED 45 mg for 6-month administration the most common (≥4%) adverse reactions were: injection site reactions, headache, psychiatric events, abdominal pain, diarrhea, hemorrhage, nausea and vomiting, pyrexia, pruritus, pain in extremity, rash, back pain, ligament sprain, weight increased, fracture, breast tenderness, insomnia, chest pain, and hyperhidrosis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. LUPRON DEPOT-PED for 1-month administration LUPRON DEPOT-PED 1-month administration was evaluated in a pivotal, open label, multicenter study in which 55 (49 female and 6 male) pediatric patients with central precocious puberty were enrolled. The age ranged from 1 to 8 years of age at the beginning of treatment; the mean age for females was 6.8 years (range: 1 to 9 years) and the mean age for males was 7.5 years (range: 4 to 9 years); 61.8% were Caucasian; 20% Black; 1.8% Oriental; and 16.4% Hispanic. Adverse reactions that occurred in ≥2% of patients are shown in Table 2. Table 2. Adverse Reactions Occurring in ≥2% in Pediatric Patients with CPP Receiving LUPRON DEPOT-PED 1-month % of Patients (N = 421) Injection Site Reactions Including Abscess* 9 Emotional Lability 5 Headache 3 General Pain 3 Acne/Seborrhea 3 Rash Including Erythema Multiforme 3 Vaginitis/Vaginal Bleeding/Vaginal Discharge 3 Vasodilation 2 * Most events were mild or moderate in severity. Less Common Adverse Reactions The following adverse reactions were reported in less than 2% of the patients and are listed below by body system. Body as a Whole – aggravation of preexisting tumor and decreased vision, allergic reaction, body odor, fever, flu syndrome, hypertrophy, infection; Cardiovascular System – bradycardia, hypertension, peripheral vascular disorder, syncope; Digestive System – constipation, dyspepsia, dysphagia, gingivitis, increased appetite, nausea/vomiting; Endocrine System – accelerated sexual maturity, feminization, goiter; Hemic and Lymphatic System – purpura; Metabolic and Nutritional Disorders – growth retarded, peripheral edema, weight gain; Musculoskeletal System – arthralgia, joint disorder, myalgia, myopathy; Nervous System – hyperkinesia, somnolence; Psychiatric System – depression, nervousness; Respiratory System – asthma, epistaxis, pharyngitis, rhinitis, sinusitis; Integumentary System (Skin an …

7 DRUG INTERACTIONS 7.1 Drug Interactions No pharmacokinetic-based drug-drug interaction studies have been conducted with LUPRON DEPOT-PED [see C linical P harmacology ( 12.3 ) ] . 7.2 Drug-Laboratory Test Interactions Administration of LUPRON DEPOT-PED in therapeutic doses results in suppression of the pituitary-gonadal system. Therefore, diagnostic tests of pituitary gonadotropic and gonadal functions conducted during treatment and up to six months after discontinuation of LUPRON DEPOT-PED may be affected. Normal pituitary-gonadal function is usually restored within six months after treatment with LUPRON DEPOT-PED is discontinued.

7.1 Drug Interactions No pharmacokinetic-based drug-drug interaction studies have been conducted with LUPRON DEPOT-PED [see C linical P harmacology ( 12.3 ) ] .

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary LUPRON DEPOT-PED is contraindicated in pregnancy [see Contraindications ( 4 ) ]. LUPRON DEPOT-PED may cause fetal harm, when administered to a pregnant woman, based on findings from animal studies and the drug’s mechanism of action [see Clinical Pharmacology ( 12.1 ) ]. The available data from published clinical studies and case reports and from the pharmacovigilance database on exposure to LUPRON DEPOT-PED during pregnancy are insufficient to assess the risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Based on animal reproduction studies, LUPRON DEPOT-PED may be associated with an increased risk of pregnancy complications, including early pregnancy loss and fetal harm. In animal reproduction studies, subcutaneous administration of leuprolide acetate to rabbits during the period of organogenesis caused embryo-fetal toxicity, decreased fetal weights and a dose-dependent increase in major fetal abnormalities in animals at doses less than the recommended human dose based on body surface area using an estimated daily dose. A similar rat study also showed increased fetal mortality and decreased fetal weights but no major fetal abnormalities at doses less than the recommended human dose based on body surface area using an estimated daily dose ( see Data ) . 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 When administered on day 6 of pregnancy at test dosages of 0.00024 mg/kg, 0.0024 mg/kg, and 0.024 mg/kg (doses less than the recommended human dose) to rabbits, leuprolide acetate produced a dose-related increase in malformations comprised primarily of segmental and fusion defects of the skeleton and skull. Similar studies in rats failed to demonstrate an increase in fetal malformations. There was increased fetal mortality and decreased fetal weights with the two higher doses of leuprolide acetate in rabbits and with the highest dose (0.024 mg/kg) in rats. 8.2 Lactation Risk Summary There are no data on the presence of leuprolide acetate in either animal or human milk, the effects on the breastfed infants, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LUPRON DEPOT-PED and any potential adverse effects on the breastfed infant from LUPRON DEPOT-PED or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Pregnancy Testing Exclude pregnancy in women of reproductive potential prior to initiating LUPRON DEPOT-PED if clinically indicated [see Use in Specific Populations ( 8.1 ) ] . Contraception Females LUPRON DEPOT-PED may cause embryo-fetal harm when administered during pregnancy. LUPRON DEPOT-PED is not a contraceptive. If contraception is indicated, advise females of reproductive potential to use a non-hormonal method of contraception during treatment with LUPRON DEPOT-PED [see Use in Specific Populations ( 8.1 ) ] . Infertility Based on its pharmacodynamic effects of decreasing secretion of gonadal steroids, fertility is expected to be decreased while on treatment with LUPRON DEPOT-PED. Clinical and pharmacologic studies in adults (>18 years) with leuprolide acetate and similar analogs have shown reversibility of fertility suppression when the drug is discontinued after continuous administration for periods of up to 24 weeks [see Clinical Pharmacology ( 12.2 ) ]. There is no evidence that pregnancy rates are affected following discontinuation of LUPRON DEPOT-PED. Animal studies (prepubertal and adult rats and monkeys) with leuprolide acetate and other GnRH analogs have shown functional recovery of fertility suppression. 8.4 Pediatric Use The safety and effect …

12.1 Mechanism of Action Leuprolide acetate, a GnRH agonist, acts as a potent inhibitor of gonadotropin secretion (LH and follicle stimulating hormone (FSH)) when given continuously in therapeutic doses.

11 DESCRIPTION LUPRON DEPOT-PED contains active ingredient, leuprolide, in the form of acetate salt, a gonadotropin-releasing hormone (GnRH) agonist. It is a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH or LH-RH). The analog possesses greater potency than the natural hormone. The chemical name of leuprolide acetate is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate, which has molecular formula of C 59 H 84 N 16 O 12 .(C 2 H 4 O 2 ) n , n=1 or 2, with the following structural formula: LUPRON DEPOT-PED for 1-month administration LUPRON DEPOT-PED is available in a prefilled dual-chamber single-dose syringe containing sterile lyophilized microsphere powder incorporated in a biodegradable lactic acid/glycolid acid copolymer which, when mixed with diluent, becomes a suspension for intramuscular injection. When mixed with 1 milliliter of accompanying diluent, LUPRON DEPOT-PED for 1-month administration is administered as a single-dose intramuscular injection. The front chamber of LUPRON DEPOT-PED 7.5 mg, 11.25 mg, and 15 mg a prefilled dual-chamber syringe contains leuprolide acetate (7.5 mg equivalent to 6.83-7.15 mg leuprolide / 11.25 mg equivalent to 10.24 – 10.72 mg leuprolide / 15 mg equivalent to 13.65 – 14.30 mg leuprolide), purified gelatin (1.3/1.95/2.6 mg), DL-lactic and glycolic acids copolymer (66.2/99.3/132.4 mg), and D-mannitol (13.2/19.8/26.4 mg). The second chamber of diluent contains carboxymethylcellulose sodium (5 mg), D-mannitol (50 mg), polysorbate 80 (1 mg), water for injection, USP, and glacial acetic acid, USP to control pH. LUPRON DEPOT-PED for 3-month administration LUPRON DEPOT-PED 11.25 mg or 30 mg for 3-month administration is available in a prefilled dual-chamber single-dose syringe containing sterile lyophilized microsphere powder incorporated in a biodegradable lactic acid/glycolid acid copolymer which, when mixed with diluent, becomes a suspension for intramuscular injection. When mixed with 1.5 milliliters of accompanying diluent, LUPRON DEPOT-PED for 3-month administration is administered as a single-dose intramuscular injection. The front chamber of LUPRON DEPOT-PED 11.25 mg for 3-month administration prefilled dual-chamber syringe contains leuprolide acetate (11.25 mg, equivalent to 10.24 - 10.72 mg leuprolide), D-mannitol (19.45 mg), and polylactic acid (99.3 mg). The second chamber of diluent contains carboxymethylcellulose sodium (7.5 mg), D-mannitol (75.0 mg), polysorbate 80 (1.5 mg), water for injection, USP, and glacial acetic acid, USP to control pH. The front chamber of LUPRON DEPOT-PED 30 mg for 3-month administration prefilled dual-chamber syringe contains leuprolide acetate (30 mg, equivalent to 27.30 - 28.59 mg leuprolide), D-mannitol (51.9 mg), and polylactic acid (264.8 mg). The second chamber of diluent contains carboxymethylcellulose sodium (7.5 mg), D-mannitol (75.0 mg), polysorbate 80 (1.5 mg), water for injection, USP, and glacial acetic acid, USP to control pH. LUPRON DEPOT-PED for 6-month administration LUPRON DEPOT-PED 45 mg for 6-month administration is available in a prefilled dual-chamber syringe containing sterile lyophilized microspheres which, when mixed with diluent, become a suspension intended as an intramuscular injection. The front chamber of LUPRON DEPOT-PED 45 mg for 6-month administration prefilled dual-chamber syringe contains leuprolide acetate (45 mg, equivalent to 40.95 - 42.89 mg leuprolide), D-mannitol (39.7 mg), polylactic acid (169.9 mg), and stearic acid (10.1 mg). The second chamber of diluent contains carboxymethylcellulose sodium (7.5 mg), D-mannitol (75.0 mg), polysorbate 80 (1.5 mg), water for injection, USP, and glacial acetic acid, USP to control pH. Lupron structure

10 OVERDOSAGE No specific antidotes for LUPRON DEPOT-PED are known. Contact Poison Control (1-800-222-1222) for latest recommendations. In cases of overdosage, standard of care monitoring and management principles should be followed.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied LUPRON DEPOT-PED for depot suspension is supplied in a single dose, prefilled dual-chamber syringe containing a white lyophilized powder and a colorless diluent for reconstitution as follows (Table 8): Table 8. LUPRON DEPOT-PED Product Presentations LUPRON DEPOT-PED 7.5 mg, 11.25 mg, or 15 mg for 1- M onth Administration Kit Type Strength NDC Number 1-month kit 7.5 mg NDC 0074-2108-03 11.25 mg NDC 0074-2282-03 15 mg NDC 0074-2440-03 LUPRON DEPOT-PED 11.25 mg or 30 mg for 3- M onth Administration 3-month kit 11.25 mg NDC 0074-3779-03 30 mg NDC 0074-9694-03 LUPRON DEPOT-PED 45 mg for 6-Month Administration 6-month kit 45 mg NDC 0074-3575-01 Each kit contains: one single-dose, prefilled dual-chamber syringe containing 23 gauge 11⁄2 inch needle with LuproLoc ® safety device one plunger two alcohol swabs population, dose and frequency confirmation insert a complete prescribing information enclosure Storage and Handling Prior to reconstitution, store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. After reconstitution, use immediately [see Dosage and Administration ( 2.5 , 2.6 ) ].