Leuprolide Acetate

FDA Drug Information • Also known as: Eligard, Fensolvi, Leuprolide Acetate, Leuprolide Acetate Depot, Lupron Depot, Lupron Depot-Ped,...

Brand Names: Eligard, Fensolvi, Leuprolide Acetate, Leuprolide Acetate Depot, Lupron Depot, Lupron Depot-Ped, Lutrate Depot, Vabrinty
Route: SUBCUTANEOUS
Dosage Form: INJECTION, SUSPENSION, EXTENDED RELEASE
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION FENSOLVI for injectable suspension is a sterile polymeric matrix formulation of leuprolide acetate, a GnRH agonist, for subcutaneous use. It is designed to deliver leuprolide acetate at a controlled rate over a six-month therapeutic period. Leuprolide acetate is a synthetic nonapeptide analog of naturally occurring gonadotropin releasing hormone. The analog possesses greater potency than the natural hormone. The chemical name is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate (salt) with the following structural formula: FENSOLVI is prefilled and supplied in two separate, sterile syringes whose contents are mixed immediately prior to administration. The two syringes are joined and the single dose product is mixed until it is homogenous. FENSOLVI is administered subcutaneously, where it forms a solid drug delivery depot. One syringe contains the ATRIGEL Delivery System and the other contains the leuprolide acetate. ATRIGEL is a polymeric (non-gelatin containing) delivery system consisting of a biodegradable poly(DL-lactide-co-glycolide) (PLG) polymer formulation dissolved in the biocompatible solvent, N-methyl-2-pyrrolidone (NMP). Refer to Table 3 for the delivery system composition and reconstituted product formulation for FENSOLVI product. Table 3: FENSOLVI Delivery System Composition and Reconstituted Product Formulation ATRIGEL Delivery System Syringe Polymer PLG Polymer description Copolymer with hexanediol Polymer DL-lactide to glycolide molar ratio 85:15 Reconstituted Product Polymer delivered 165 mg NMP delivered 165 mg Leuprolide acetate delivered 45 mg Approximate leuprolide free base equivalent 42 mg Approximate administered formulation weight 375 mg Approximate injection volume 0.375 mL formula

What Is Leuprolide Acetate Used For?

1 INDICATIONS AND USAGE FENSOLVI is indicated for the treatment of pediatric patients 2 years of age and older with central precocious puberty (CPP). FENSOLVI is a gonadotropin releasing hormone (GnRH) agonist indicated for the treatment of pediatric patients 2 years of age and older with central precocious puberty.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Must be administered by a healthcare professional. ( 2.1 ) The dose of FENSOLVI is 45 mg administered by subcutaneous injection once every six months. ( 2.1 ) Monitor response to FENSOLVI with a GnRH agonist stimulation test, basal serum luteinizing hormone (LH) levels or serum concentration of sex steroid levels at 1 to 2 months following initiation of therapy and as needed to confirm adequate suppression of pituitary gonadotropins, sex steroids, and progression of secondary sexual characteristics. ( 2.2 ) Measure height every 3 to 6 months and monitor bone age periodically. ( 2.2 ) See Full Prescribing Information for reconstitution and administration instructions. ( 2.3 , 2.4 ) 2.1 Dosing Information FENSOLVI must be administered by a healthcare professional. The dose of FENSOLVI is 45 mg administered by subcutaneous injection once every six months. Discontinue FENSOLVI treatment at the appropriate age of onset of puberty. 2.2 Monitoring Monitor response to FENSOLVI with a GnRH agonist stimulation test, basal serum luteinizing hormone (LH) levels or serum concentration of sex steroid levels at 1 to 2 months following initiation of therapy and as needed to confirm adequate suppression of pituitary gonadotropins, sex steroids, and progression of secondary sexual characteristics. Measure height (for calculation of growth velocity) every 3 to 6 months and monitor bone age periodically. Noncompliance with drug regimen or inadequate dosing may lead to gonadotropins and/or sex steroids increasing above prepubertal levels resulting in inadequate control of the pubertal process. If the dose of FENSOLVI is not adequate, switching to an alternative GnRH agonist for the treatment of CPP with the ability for dose adjustment may be necessary. 2.3 Reconstitution Instructions Use aseptic technique including gloves for reconstitution and administration. Allow the product to reach room temperature before reconstitution to allow for easier administration. Once reconstituted, the concentration is 45 mg/0.375 mL. Administer the product within 30 minutes or discard. FENSOLVI is packaged in a carton containing two trays and this package insert: Table 1: Contents of the Two Trays in the FENSOLVI Carton Syringe A Tray Syringe B Tray Syringe A is prefilled with diluent for reconstitution (ATRIGEL Delivery System) Syringe B is prefilled with 45 mg lyophilized leuprolide acetate powder White plunger rod (To be used with Syringe B) Safety needle (18G x 5/8") Desiccant pack Desiccant pack Follow the instructions below to prepare FENSOLVI: 1. On a clean field, open both trays by tearing off the foil from the corners and removing the contents. Discard the desiccant pack(s). Open the safety needle package by peeling back the paper tab. 2. Pull out (do not unscrew) the short blue plunger rod with attached gray stopper from Syringe B and discard. 3. Gently screw the white plunger rod into the remaining gray stopper in Syringe B. 4. Unscrew and...

Side Effects (Adverse Reactions)

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 )] . Pseudotumor Cerebri (Idiopathic Intracranial Hypertension) [ see Warnings and Precautions ( 5.4 )] The most common adverse reactions (≥5%) were: injection site pain, nasopharyngitis, pyrexia, headache, cough, abdominal pain, injection site erythema, nausea, constipation, vomiting, upper respiratory tract infection, bronchospasm, productive cough, and hot flush. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Tolmar Pharmaceuticals, Inc. at 1-844-4TOLMAR (1-844-486-5627) 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 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. FENSOLVI was evaluated in an uncontrolled, open-label, single-arm clinical trial in which 64 pediatric patients with CPP received at least one dose of FENSOLVI. The age ranged from 4 to 9 years at start of treatment; 62 patients were female and 2 were male; 53% White; 23% Black; 8% American Indian or Alaska Native; 5% Asian; 2% Native Hawaiian or Other Pacific Islander. 56% of the subjects self-identified as Hispanic or Latino ethnicity. Adverse reactions that occurred in ≥ 5% of patients are shown in Table 2. Table 2: Adverse Reactions Occurring in ≥ 5% of Patients Treated with FENSOLVI in an Open-Label, Single-Arm Trial Adverse Reactions % of Patients (N=64) Injection site pain 31 Nasopharyngitis 22 Pyrexia 17 Headache 16 Cough 13 Abdominal pain 9 Injection site erythema 9 Nausea 8 Constipation 6 Vomiting 6 Upper respiratory tract infection 6 Bronchospasm 6 Productive cough 6 Hot flush 5 Other Adverse Reactions: Psychiatric Emotional disorder (2%) and irritability (2%) 6.2 Postmarketing Experience The following adverse reactions have been identifed during postapproval use of leuprolide acetate or FENSOLVI. 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. Allergic Reactions: anaphylactic, rash, urticaria, and photosensitivity reactions. General : chest pain, weight increase, weight decrease, decreased appetite, fatigue. Laboratory Abnormalities: decreased WBC. Metabolic : diabetes mellitus. Musculoskeletal and Connective Tissue : arthralgia, epiphysiolysis, muscle spasms, myalgia. Neurologic: neuropathy peripheral, convulsion, paralysis, insomnia, pseudotumor cerebri (idiopathic intracranial hypertension). Psychiatric: 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. Skin and Subcutaneous Tissue : injection site reactions including induration and abscess, flushing, hyperhidrosis. Reproductive System: vaginal bleeding, breast enlargement. Vascular : hypertension, hypotension. Respiratory: dyspnea.

Drug Interactions

7 DRUG INTERACTIONS No pharmacokinetic drug-drug interaction studies have been conducted with FENSOLVI.

Contraindications

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

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary FENSOLVI is contraindicated in pregnancy [see Contraindications ( 4 )] . FENSOLVI may cause fetal harm 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 leuprolide acetate during pregnancy are insufficient to assess the risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Based on animal reproduction studies, leuprolide acetate 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% to 4% and 15% to 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 (1/3255 to 1/33 of the human dose) to rabbits, leuprolide acetate produced a dose-related increase in major fetal abnormalities. 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...

Overdosage

10 OVERDOSAGE No specific antidotes for FENSOLVI are known. Contact Poison Control (1-800-222-1222) for latest recommendations.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING For injectable suspension, 45 mg of leuprolide acetate supplied in a kit (NDC 62935-153-50) containing: Syringe A Tray Syringe B Tray Syringe A is prefilled with diluent for reconstitution (ATRIGEL Delivery System) Syringe B is prefilled with 45 mg lyophilized leuprolide acetate powder White plunger rod (To be used with Syringe B) Safety needle (18G x 5/8") Desiccant pack Desiccant pack Store refrigerated at 2 - 8 °C (35.6 – 46.4 °F). Once outside the refrigerator, this product may be stored in its original packaging at room temperature 15 – 30 °C (59 – 86 °F) for up to eight weeks prior to reconstitution and administration.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.