Lupron Depot 3.75 MG in 1 ML (1 month) Prefilled Syringe
Generic Name: LEUPROLIDE ACETATE
Brand Name: Lupron Depot
DRUG INTERACTIONS
7 No drug-drug interaction studies have been conducted with LUPRON DEPOT 3.75 mg.
DESCRIPTION
11 Leuprolide acetate is a synthetic nonapeptide analog of gonadotropin-releasing hormone [GnRH or luteinizing hormone releasing hormone (LH-RH)], a GnRH agonist.
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: LUPRON DEPOT 3.75 mg (leuprolide acetate for depot suspension for injection) is available in a prefilled dual-chamber syringe containing sterile lyophilized microspheres powder which, when mixed with diluent, become a suspension intended as an IM injection.
The front chamber of LUPRON DEPOT 3.75 mg prefilled dual-chamber syringe contains leuprolide acetate for depot suspension (3.75 mg), purified gelatin (0.65 mg), DL-lactic and glycolic acids copolymer (33.1 mg) and D-mannitol (6.6 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.
During the manufacture of LUPRON DEPOT 3.75 mg, acetic acid is lost, leaving the peptide.
structural formula
CLINICAL STUDIES
14 The safety and efficacy of LUPRON DEPOT 3.75 mg for the indicated populations has been established based on adequate and well-controlled studies in adults (See Table 8 ) of LUPRON DEPOT 3.75 mg [see Indications and Usage ( 1 ) ] .
Figure 1 14.1 Endometriosis LUPRON DEPOT 3.75 mg Monotherapy In controlled clinical studies, LUPRON DEPOT 3.75 mg monthly for six months was shown to be comparable to danazol 800 mg/day in relieving the clinical sign/symptoms of endometriosis (pelvic pain, dysmenorrhea, dyspareunia, pelvic tenderness, and induration) and in reducing the size of endometrial implants as evidenced by laparoscopy.
The clinical significance of a decrease in endometriotic lesions is not known, and laparoscopic staging of endometriosis does not necessarily correlate with the severity of symptoms.
LUPRON DEPOT 3.75 mg monthly induced amenorrhea in 74% and 98% of the women after the first and second month of treatment, respectively.
Most of the remaining women reported episodes of only light bleeding or spotting.
In the first, second and third post-treatment months, normal menstrual cycles resumed in 7%, 71% and 95% of women, respectively, excluding those who became pregnant.
Figure 1 illustrates the percent of women with symptoms at baseline, final treatment visit and sustained relief at 6 and 12 months following discontinuation of treatment for the various symptoms evaluated during the two controlled clinical studies.
A total of 166 women received LUPRON DEPOT 3.75 mg.
Seventy-five percent (N=125) of these elected to participate in the follow-up period.
Of these women, 36% and 24% are included in the 6-month and 12-month follow-up analysis, respectively.
All the women who had a pain evaluation at baseline and at least of one treatment visit are included in the Baseline (B) and final treatment visit (F) analysis.
Figure 1.
Percent of Women with Signs/Symptoms of Endometriosis at Baseline, Final Treatment Visit, and After 6 and 12 Months of Follow-Up, LUPRON DEPOT 3.75 mg Monthly for Six Months LUPRON DEPOT with Norethindrone Acetate Add-Back Therapy Two clinical studies with treatment duration of 12 months were conducted to evaluate the effect of co-administration of LUPRON DEPOT 3.75 mg and norethindrone acetate on the loss of bone mineral density (BMD) associated with LUPRON DEPOT 3.75 mg and on the efficacy of LUPRON DEPOT in relieving symptoms of endometriosis.
All women in these studies received calcium supplementation with 1000 mg elemental calcium.
A total of 242 women were treated with monthly administration of LUPRON DEPOT 3.75 mg (13 injections) and 191 of them were co-administered 5 mg norethindrone acetate taken daily.
The population age range was 17-43 years old.
The majority of women were Caucasian (87%).
One co-administration study was a controlled, randomized and double-blind study included 51 women treated monthly with LUPRON DEPOT 3.75 mg alone and 55 women treated monthly with LUPRON DEPOT 3.75 mg plus norethindrone acetate daily.
Women in this trial were followed for up to 24 months after completing one year of treatment.
The other study was an open-label single arm clinical study in 136 women of one year of treatment with LUPRON DEPOT 3.75 mg monthly and daily norethindrone acetate 5 mg, with follow-up for up to 12 months after completing treatment.
See Table 8 .
The assessment of efficacy was based on the investigator’s or the woman’s monthly assessment of five signs or symptoms of endometriosis (dysmenorrhea, pelvic pain, deep dyspareunia, pelvic tenderness and pelvic induration).
Table 8 below provides detailed efficacy data regarding relief of symptoms of endometriosis based on the two studies of co-administration of LUPRON DEPOT 3.75 mg monthly and norethindrone acetate 5 mg daily.
Table 8.
Effect of LUPRON DEPOT and Norethindrone Acetate on the Symptoms of Endometriosis and Mean Clinical Severity Scores Percent of Women with Symptoms Clinical Pain Severity Score Baseline Final Baseline Final Variable Study Group N 1 (%) 2 (%) N 1 Value 3 Change Dysmenorrhea Controlled Study LD* 4 51 (100) (4) 50 3.2 -2.0 LD/N† 55 (100) (4) 54 3.1 -2.0 Open Label Study LD/N 5 136 (99) (9) 134 3.3 -2.1 Pelvic Pain Controlled Study LD 4 51 (100) (66) 50 2.9 -1.1 LD/N 55 (96) (56) 54 3.1 -1.1 Open Label Study LD/N 5 136 (99) (63) 134 3.2 -1.2 Deep Dyspareunia Controlled Study LD 4 42 (83) (37) 25 2.4 -1.0 LD/N 43 (84) (45) 30 2.7 -0.8 Open Label Study LD/N 5 102 (91) (53) 94 2.7 -1.0 Pelvic Tenderness Controlled Study LD 4 51 (94) (34) 50 2.5 -1.0 LD/N 54 (91) (34) 52 2.6 -0.9 Open Label Study LD/N 5 136 (99) (39) 134 2.9 -1.4 Pelvic Induration Controlled Study LD 4 51 (51) (12) 50 1.9 -0.4 LD/N 54 (46) (17) 52 1.6 -0.4 Open Label Study LD/N 5 136 (75) (21) 134 2.2 -0.9 * LD = LUPRON DEPOT 3.75 mg assessment † LD/N = LUPRON DEPOT 3.75 mg plus norethindrone acetate 5 mg 1 Number of women that were included in the assessment 2 Percentage of women with the symptom/sign 3 Value description: 1=none; 2= mild; 3= moderate; 4= severe 4 12-month treatment followed by up to 24 months of follow up 5 12-month treatment followed by up to 12 months of follow up Suppression of menses (menses was defined as three or more consecutive days of menstrual bleeding) was maintained throughout treatment in 84% and 73% of women receiving leuprolide acetate and norethindrone acetate, in the controlled study and open label study, respectively.
The median time for menses resumption after treatment with leuprolide acetate and norethindrone acetate was 8 weeks.
Changes in Bone Density The effect of LUPRON DEPOT 3.75 mg and norethindrone acetate on bone mineral density was evaluated by dual energy x-ray absorptiometry (DEXA) scan in the two clinical trials.
For the open-label study, success in mitigating BMD loss was defined as the lower bound of the 95% confidence interval around the change from baseline at one year of treatment not to exceed -2.2%.
The bone mineral density data of the lumbar spine from these two studies are presented in Table 9 .
Table 9.
Mean Percent Change from Baseline in Bone Mineral Density of Lumbar Spine LUPRON DEPOT 3.75 mg (LD only) LUPRON DEPOT 3.75 mg plus norethindrone acetate 5 mg daily (LD/N) Controlled Study Controlled Study Open Label Study N Change Mean (95% CI) # N Change Mean (95% CI) # N Change Mean (95% CI) # Week 24* 41 -3.2% (-3.8, -2.6) 42 -0.3% (-0.8, 0.3) 115 -0.2% (-0.6, 0.2) Week 52† 29 -6.3% (-7.1, -5.4) 32 -1.0% (-1.9, -0.1) 84 -1.1% (-1.6, -0.5) * Includes on-treatment measurements that fell within 2 to 252 days after the first day of treatment.
† Includes on-treatment measurements >252 days after the first day of treatment.
# 95% CI: 95% Confidence Interval The change in BMD following discontinuation of treatment is shown in Table 10 .
Table 10.
Mean Percent Change from Baseline in BMD of Lumbar Spine in Post-Treatment Follow-up Period 1 Post Treatment Measurement Controlled Study Open Label Study LD-Only LD/N LD/N N Mean % Change 95% CI (%) 2 N Mean % Change 95% CI (%) N Mean % Change 95% CI (%) 2 Month 8 19 -3.3 (-4.9, -1.8) 23 -0.9 (-2.1, 0.4) 89 -0.6 (-1.2, 0.0) Month 12 16 -2.2 (-3.3, -1.1) 12 -0.7 (-2.1, 0.6) 65 0.1 (-0.6, 0.7) 1 Patients with post treatment measurements 2 95% CI (2-sided) of percent change in BMD values from baseline These clinical studies demonstrated that co-administration of leuprolide acetate and norethindrone acetate 5 mg daily is effective in significantly reducing the loss of bone mineral density that occurs with LUPRON DEPOT 3.75 mg and in relieving symptoms of endometriosis.
14.2 Fibroids LUPRON DEPOT 3.75 mg monthly for a period of three to six months was studied in four controlled clinical trials.
In one of these clinical studies, enrollment was based on hematocrit ≤ 30% and/or hemoglobin ≤ 10.2 g/dL.
Administration of LUPRON DEPOT 3.75 mg monthly, concomitantly with iron, produced an increase of ≥ 6% hematocrit and ≥ 2 g/dL hemoglobin in 77% of women at three months of therapy.
The mean change in hematocrit was 10.1% and the mean change in hemoglobin was 4.2 g/dL.
Clinical response was judged to be a hematocrit of ≥ 36% and hemoglobin of ≥ 12 g/dL, thus allowing for autologous blood donation prior to surgery.
At two and three months, respectively, 71% and 75% of women met this criterion (Table 11 ).
These data suggest however, that some women may benefit from iron alone or 1 to 2 months of LUPRON DEPOT 3.75 mg.
Table 11.
Percent of Women Achieving Hematocrit ≥ 36% and Hemoglobin ≥ 12 g/dL Treatment Group Week 4 Week 8 Week 12 LUPRON DEPOT 3.75 mg with Iron (N=104) 40* 71† 75* Iron Alone (N=98) 17 39 49 * P-Value < 0.01 † P-Value < 0.001 Excessive vaginal bleeding (menorrhagia or menometrorrhagia) decreased in 80% of women at three months.
Episodes of spotting and menstrual-like bleeding were noted in 16% of women at final visit.
In this same study, a decrease in uterine volume and myoma volume of ≥25% was seen in 60% and 54% of women, respectively.
The mean fibroid diameter was 6.3 cm at pretreatment and decreased to 5.6 cm at the end of treatment.
LUPRON DEPOT 3.75 mg was found to relieve symptoms of bloating, pelvic pain, and pressure.
In three other controlled clinical trials, enrollment was not based on hematologic status.
Mean uterine volume decreased by 41% and myoma volume decreased by 37% at final visit as evidenced by ultrasound or MRI.
The mean fibroid diameter was 5.6 cm at pretreatment and decreased to 4.7 cm at the end of treatment.
These women also experienced a decrease in symptoms including excessive vaginal bleeding and pelvic discomfort.
Ninety-five percent of these women became amenorrheic with 61%, 25%, and 4% experiencing amenorrhea during the first, second, and third treatment months respectively.
In addition, post-treatment follow-up was carried out in one clinical trial for a small percentage of women on LUPRON DEPOT 3.75 mg (N=46) among the 77% who demonstrated a ≥ 25% decrease in uterine volume while on therapy.
Menses usually returned within two months of cessation of therapy.
Mean time to return to pretreatment uterine size was 8.3 months.
Regrowth did not appear to be related to pretreatment uterine volume.
Changes in Bone Density In one of the studies for fibroids described above, when LUPRON DEPOT 3.75 mg was administered for three months in women with uterine fibroids, vertebral trabecular bone mineral density, as assessed by quantitative digital radiography (QDR), revealed a mean decrease of 2.7% compared with baseline.
Six months after discontinuation of therapy, a trend toward recovery was observed.
HOW SUPPLIED
16 /STORAGE AND HANDLING Each LUPRON DEPOT 3.75 mg kit (NDC 0074-3641-03) contains: one prefilled dual-chamber syringe one plunger two alcohol swabs Each single-dose dual chamber syringe contains sterile white lyophilized microsphere powder of 3.75 mg of leuprolide acetate incorporated in a biodegradable polymer in one chamber and a colorless diluent (1 mL) in the other chamber.
When mixed with the diluent, LUPRON DEPOT 3.75 mg for injection, is administered as a single IM injection.
Store between 20° to 25°C (68° to 77°F).
Excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature] .
RECENT MAJOR CHANGES
Warnings and Precautions, Severe Cutaneous Adverse Reactions ( 5.3 ) 9/2025
GERIATRIC USE
8.5 Geriatric Use LUPRON DEPOT 3.75 mg is not indicated in postmenopausal women and has not been studied in this population.
DOSAGE FORMS AND STRENGTHS
3 For Injection: 3.75 mg of leuprolide acetate as a white lyophilized microsphere powder for reconstitution in a single dose prefilled dual chamber syringe; with one chamber containing the lyophilized powder and the other chamber containing the clear diluent.
Depot suspension for injection: 3.75 mg lyophilized powder for reconstitution in a dual-chamber syringe.
( 3 )
MECHANISM OF ACTION
12.1 Mechanism of Action Leuprolide acetate is a long-acting GnRH analog.
A single monthly injection of LUPRON DEPOT 3.75 mg results in an initial stimulation followed by a prolonged suppression of pituitary gonadotropins.
Repeated dosing of LUPRON DEPOT 3.75 mg at monthly intervals results in decreased secretion of gonadal steroid.
Consequently, tissues and functions that depend on gonadal steroids for their maintenance become quiescent.
This effect is reversible on discontinuation of drug therapy.
Leuprolide acetate is not active when given orally.
INDICATIONS AND USAGE
1 LUPRON DEPOT 3.75 mg is a gonadotropin-releasing hormone (GnRH) agonist indicated for: Endometriosis Management of endometriosis, including pain relief and reduction of endometriotic lesions.
( 1.1 ) In combination with a norethindrone acetate for initial management of the painful symptoms of endometriosis and for management of recurrence of symptoms.
( 1.1 ) Limitations of Use: The total duration of therapy with LUPRON DEPOT 3.75 mg plus add-back therapy should not exceed 12 months due to concerns about adverse impact on bone mineral density.
( 1.1 , 2.1 , 5.1 ) Uterine Leiomyomata (Fibroids) Concomitant use with iron therapy for preoperative hematologic improvement of women with anemia caused by fibroids for whom three months of hormonal suppression is deemed necessary.
( 1.2 ) Limitations of Use: LUPRON DEPOT 3.75 mg is not indicated for combination use with norethindrone acetate add-back therapy for the preoperative hematologic improvement of women with anemia caused by heavy menstrual bleeding due to fibroids.
( 1.2 ) 1.1 Endometriosis Monotherapy LUPRON DEPOT 3.75 mg is indicated for management of endometriosis, including pain relief and reduction of endometriotic lesions.
In Combination with Norethindrone Acetate LUPRON DEPOT 3.75 mg in combination with norethindrone acetate is indicated for initial management of the painful symptoms of endometriosis and for management of recurrence of symptoms.
Use of norethindrone acetate in combination with LUPRON DEPOT 3.75 mg is referred to as add-back therapy, and is intended to reduce the loss of bone mineral density (BMD) and reduce vasomotor symptoms associated with use of LUPRON DEPOT 3.75 mg.
Limitations of Use : The total duration of therapy with LUPRON DEPOT 3.75 mg plus add-back therapy should not exceed 12 months due to concerns about adverse impact on bone mineral density [see Dosage and Administration ( 2.1 ) and Warnings and Precautions ( 5.1 ) ] .
1.2 Uterine Leiomyomata (Fibroids) LUPRON DEPOT 3.75 mg, used concomitantly with iron therapy, is indicated for the preoperative hematologic improvement of women with anemia caused by fibroids for whom three months of hormonal suppression is deemed necessary.
Consider a one-month trial period on iron alone, as some women will respond to iron alone [see Clinical Studies ( 14.2 )] .
LUPRON DEPOT 3.75 mg may be added if the response to iron alone is considered inadequate.
Limitations of Use : LUPRON DEPOT 3.75 mg is not indicated for combination use with norethindrone acetate add-back therapy for the preoperative hematologic improvement of women with anemia caused by heavy menstrual bleeding due to fibroids [see Dosage and Administration ( 2.1 )] .
PEDIATRIC USE
8.4 Pediatric Use Safety and effectiveness of LUPRON DEPOT 3.75 mg for management of endometriosis and the preoperative hematologic improvement of women with anemia caused by fibroids have been established in females of reproductive age.
Efficacy is expected to be the same for postpubertal adolescents under the age of 18 as for users 18 years and older.
The safety and effectiveness of LUPRON DEPOT 3.75 mg for these indications have not been established in premenarcheal pediatric patients.
PREGNANCY
8.1 Pregnancy Risk Summary LUPRON DEPOT 3.75 mg is contraindicated in pregnancy [see Contraindications ( 4 ) ] .
LUPRON DEPOT 3.75 mg may cause fetal harm based on findings from animal studies and the drug’s mechanism of action [see Clinical Pharmacology ( 12.1 ) ] .
There are limited human data on the use of LUPRON DEPOT in pregnant women.
Based on animal reproduction studies, LUPRON DEPOT 3.75 mg 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 ] .
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 (1/300 to 1/3 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 LUPRON DEPOT in rabbits and with the highest dose (0.024 mg/kg) in rats.
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS Loss of bone mineral density (BMD): Duration of treatment is limited by risk of bone mineral density.
When using for management of endometriosis: combination use with norethindrone acetate is effective in reducing loss of BMD; do not retreat without combination norethindrone acetate.
Assess BMD before retreatment.
( 1.1 , 1.2 , 5.1 ) Embryo-Fetal Toxicity: May cause fetal harm.
Exclude pregnancy before initiating treatment if clinically indicated and discontinue use if pregnancy occurs.
Use non-hormonal methods of contraception only.
( 5.2 ) Severe Cutaneous Adverse Reactions (SCARs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), occurred in patients treated with LUPRON DEPOT.
Discontinue LUPRON DEPOT 3.75 mg if signs or symptoms of SCARs develop.
Permanently discontinue if SCARs are confirmed.
( 5.3 ) Hypersensitivity reactions, including anaphylaxis, have been reported with LUPRON DEPOT 3.75 mg.
( 5.4 ) If LUPRON is administered with norethindrone acetate, the warnings and precautions for norethindrone acetate apply to the combination regimen.
( 5.8 ) 5.1 Loss of Bone Mineral Density LUPRON DEPOT 3.75 mg induces a hypoestrogenic state that results in loss of bone mineral density (BMD), some of which may not be reversible after stopping treatment.
In women with major risk factors for decreased BMD such as chronic alcohol use (> 3 units per day), tobacco use, strong family history of osteoporosis, or chronic use of drugs that can decrease BMD, such as anticonvulsants or corticosteroids, use of LUPRON DEPOT 3.75 mg may pose an additional risk.
Carefully weigh the risks and benefits of LUPRON DEPOT 3.75 mg use in these populations.
The duration of LUPRON DEPOT 3.75 mg treatment is limited by the risk of loss of bone mineral density [see Dosage and Administration ( 2.1 )] .
When using LUPRON DEPOT 3.75 mg for the management of endometriosis, combination use of norethindrone acetate (add-back therapy) is effective in reducing the loss of BMD that occurs with leuprolide acetate [see Clinical Studies ( 14.2 )] .
Do not retreat with LUPRON DEPOT 3.75 mg without combination norethindrone acetate.
Assess BMD before retreatment.
5.2 Embryo-Fetal Toxicity Based on animal reproduction studies and the drug’s mechanism of action, LUPRON DEPOT 3.75 mg may cause fetal harm if administered to a pregnant woman and is contraindicated in pregnant women.
Exclude pregnancy prior to initiating treatment with LUPRON DEPOT 3.75 mg if clinically indicated.
Discontinue LUPRON DEPOT 3.75 mg if the woman becomes pregnant during treatment and inform the woman of potential risk to the fetus [see Contraindications ( 4 ) and Use in Specific Populations ( 8.1 ) ] .
Advise women to notify their healthcare provider if they believe they may be pregnant.
When used at the recommended dose and dosing interval, LUPRON DEPOT 11.25 mg usually inhibits ovulation and stops menstruation.
Contraception, however, is not ensured by taking LUPRON DEPOT 11.25 mg.
If contraception is indicated, advise women to use non-hormonal methods of contraception while on treatment with LUPRON DEPOT 3.75 mg.
5.3 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (SCARs) have been reported in patients receiving GnRH agonists, including LUPRON DEPOT.
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 [see Adverse Reactions ( 6.2 )] .
Monitor patients for the signs and symptoms of SCARs such as fever, flu-like symptoms, mucosal lesions, progressive skin rash, or lymphadenopathy.
Advise patients of the signs and symptoms of SCARs.
If a SCAR is suspected, discontinue LUPRON DEPOT 3.75 mg.
Consult with a healthcare provider with expertise in the diagnosis and management of SCARs.
If a diagnosis of SCAR is confirmed, permanently discontinue LUPRON DEPOT 3.75 mg.
5.4 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis, have been reported with LUPRON DEPOT use.
LUPRON DEPOT 3.75 mg is contraindicated in women with a history of hypersensitivity to gonadotropin-releasing hormone (GnRH) or GnRH agonist analogs [ see Contraindications ( 4 ) and Adverse Reactions ( 6.2 )] .
In clinical trials of LUPRON DEPOT 3.75 mg, adverse events of asthma were reported in women with pre-existing histories of asthma, sinusitis, and environmental or drug allergies.
Symptoms consistent with an anaphylactoid or asthmatic process have been reported postmarketing.
5.5 Initial Flare of Symptoms Following the first dose of LUPRON DEPOT 3.75 mg, sex steroids temporarily rise above baseline because of the physiologic effect of the drug.
Therefore, an increase in symptoms may be observed during the initial days of therapy, but these should dissipate with continued therapy.
5.6 Convulsions There have been postmarketing reports of convulsions in women on GnRH agonists, including leuprolide acetate.
These included women with and without concurrent medications and comorbid conditions.
5.7 Clinical Depression Depression may occur or worsen during treatment with GnRH agonists including LUPRON DEPOT 3.75 mg [see Adverse Reactions ( 6.1 )] .
Carefully observe women for depression, especially those with a history of depression and consider whether the risks of continuing LUPRON DEPOT 3.75 mg outweigh the benefits.
Women with new or worsening depression should be referred to a mental health professional, as appropriate.
5.8 Risks Associated with Norethindrone Combination Treatment If LUPRON DEPOT 3.75 mg is administered with norethindrone acetate, the warnings and precautions for norethindrone acetate apply to this regimen.
Refer to the norethindrone acetate prescribing information for a full list of the warnings and precautions for norethindrone acetate.
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION Loss of Bone Density Advise patients about the risk of loss of bone mineral density and that treatment is limited [see Dosage and Administration ( 2.1 ) ] .
Advise patients about other factors that can increase and decrease their risk of bone mineral density loss [see Warnings and Precautions ( 5.1 ) ] .
Embryo-Fetal Toxicity Advise females of reproductive potential of the possible risk to a fetus.
Advise patients to inform healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.2 ) and Use in Special Populations ( 8.1 ) ] .
If contraception is indicated, advise females of reproductive potential to use non-hormonal contraception during treatment with LUPRON DEPOT 3.75 mg [see Use in Special Populations ( 8.3 ) ] .
Severe Cutaneous Adverse Reactions Inform patients that severe cutaneous adverse reactions (SCARs) may occur during treatment with LUPRON DEPOT 3.75 mg.
Advise patients to discontinue LUPRON DEPOT 3.75 mg and immediately contact their healthcare provider if they experience signs or symptoms of SCARs [ see Warnings and Precautions ( 5.3 ) ].
Hypersensitivity Reactions Inform patients that hypersensitivity reactions, including anaphylaxis, have been reported with LUPRON DEPOT.
Advise patients to seek appropriate medical care if symptoms of hypersensitivity reactions occur [see Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.2 ) ].
Initial Flare of Symptoms Advise patients that they may experience an increase in symptoms during the initial days of therapy.
Advise patients that these symptoms should dissipate with continued therapy [see Warnings and Precautions ( 5.5 ) ].
Convulsions Inform patients that convulsions have been reported in patients who have received LUPRON DEPOT.
Advise patients to seek medical attention in the event of a convulsion [see Warnings and Precautions ( 5.6 ) ] .
Clinical Depression Inform patients that depression may occur or worsen during treatment with GnRH agonists, including LUPRON DEPOT 3.75 mg, especially in patients with a history of depression.
Advise patients to immediately report thoughts and behaviors of concern to healthcare providers [see Warnings and Precautions ( 5.7 ) ] .
Manufactured for AbbVie Inc.
North Chicago, IL 60064 by Takeda Pharmaceutical Company Limited Osaka, Japan 540-8645 Revised 09/2025 20085416
DOSAGE AND ADMINISTRATION
2 LUPRON DEPOT 3.75 mg for 1-month administration, given by a healthcare provider as a single intramuscular injection.
LUPRON DEPOT 3.75 mg has different release characteristics than LUPRON 11.25 mg and is dosed differently.
( 2.1 ) Do not substitute LUPRON DEPOT 3.75 mg for LUPRON DEPOT 11.25 mg.
Do not administer LUPRON DEPOT 3.75 mg more frequently than once a month.
Do not give a fractional dose of the LUPRON DEPOT 11.25 mg 3-month formulation, as it is not equivalent to a single dose of the LUPRON DEPOT 3.75 mg.
Do not give a triple dose of the LUPRON DEPOT 3.75 mg, as it is not equivalent to a single dose of the LUPRON DEPOT 11.25 mg 3- month formulation.
Reconstitute LUPRON DEPOT 3.75 mg prior to use.
( 2.2 ) Endometriosis: LUPRON DEPOT 3.75 mg administered as a single intramuscular (IM) injection once every month for up to six injections (6 months of therapy).
LUPRON DEPOT may be administered alone or in combination with daily 5 mg tablet of norethindrone acetate (add-back).
( 2.1 ) If endometriosis symptoms recur after initial course of therapy, retreatment for no more than six months may be considered but only with the addition of norethindrone acetate add-back therapy.
Do not re-treat with LUPRON DEPOT 3.75 mg alone.
( 2.1 ) Fibroids: Recommended dose of LUPRON DEPOT 3.75 mg is one IM injection every month for up to three months.
( 2.1 ) Figure A Figure B Figure C Figure D Figure E Figure F Figure G 2.1 Important Use Information LUPRON DEPOT 3.75 mg must be administered by a healthcare professional.
LUPRON DEPOT 3.75 mg for 1-month administration has different release characteristics than LUPRON 11.25 mg for 3-month administration and is dosed differently.
Do not substitute LUPRON DEPOT 3.75 mg for LUPRON DEPOT 11.25 mg.
Do not administer LUPRON DEPOT 3.75 mg more frequently than once a month.
Do not give a fractional dose of the LUPRON DEPOT 11.25 mg 3-month formulation as it is not equivalent to a single dose of the LUPRON DEPOT 3.75 mg.
Do not give a triple dose of the LUPRON DEPOT 3.75 mg, as it is not equivalent to a single dose of the LUPRON DEPOT 11.25 mg 3-month formulation.
Endometriosis The initial and retreatment dosage regimens for LUPRON DEPOT 3.75 mg for the management of women with endometriosis are outlined in Table 1.
Table 1.
LUPRON DEPOT 3.75 mg, Management of Endometriosis Treatment Phase LUPRON DEPOT 3.75 mg Dosing Maximum Treatment Duration Initial Treatment 1 3.75 mg IM every 1 month for 1 to 6 doses 6 months Retreatment 2 3.75 mg IM every 1 month for 1 to 6 doses 6 months 12 MONTHS 3 TOTAL TREATMENT DURATION 1 May use LUPRON DEPOT 3.75 mg with or without norethindrone acetate 5 mg tablet taken daily.
2 Use LUPRON DEPOT 3.75 mg with norethindrone acetate for retreatment 5 mg tablet taken daily [see Warnings and Precautions ( 5.1 ) ] and assess bone mineral density (BMD) prior to retreatment.
3 Treatment should not exceed 12 months due to concerns about adverse impact on bone mineral density.
Fibroids The recommended dosage of LUPRON DEPOT 3.75 mg is one IM injection every month for up to three months.
2.2 Reconstitution and Administration for Injection of LUPRON DEPOT Reconstitute and administer the lyophilized microsphere as a single IM injection as directed below.
Visually inspect the drug product for particulate matter and discoloration prior to administration, whenever solution and container permit.
Inject the LUPRON DEPOT 3.75 mg suspension immediately or discard if not used within two hours as the suspension does not contain a preservative.
1.
Visually inspect the LUPRON DEPOT 3.75 mg powder.
Do not use the syringe if clumping or caking is evident.
A thin layer of powder on the wall of the syringe is considered normal prior to mixing with the diluent.
The diluent should appear clear.
2.
To prepare for injection, screw the white plunger into the end stopper until the stopper begins to turn (see Figure A and Figure B ).
Figure A: Figure B: 3.
Hold the syringe UPRIGHT.
Release the diluent by SLOWLY PUSHING the plunger for 6 to 8 seconds until the first middle stopper is at the blue line in the middle of the barrel (see Figure C ).
Figure C: 4.
Keep the syringe upright .
Mix the microsphere powder thoroughly by gently shaking the syringe until the powder forms a uniform suspension.
The suspension will appear milky.
If the powder adheres to the stopper or caking/clumping is present, tap the syringe with your finger to disperse.
Do not use if any of the powder has not gone into suspension (see Figure D ).
Figure D: 5.
Keep the syringe upright .
With the opposite hand pull the needle cap upward without twisting.
6.
Keep the syringe upright.
Advance the plunger to expel the air from the syringe.
The syringe is now ready for injection.
7.
After cleaning the injection site with an alcohol swab, administer the IM injection by inserting the needle at a 90-degree angle into the gluteal area, anterior thigh, or deltoid.
Injection sites should be alternated (see Figure E ).
Figure E: Note : If a blood vessel is accidentally penetrated, aspirated blood will be visible just below the luer lock (see Figure F ) and can be seen through the transparent LuproLoc ® safety device.
If blood is present, remove the needle immediately.
Do not inject the medication.
Figure F: 8.
Inject the entire contents of the syringe intramuscularly.
9.
Withdraw the needle.
Once the syringe has been withdrawn, immediately activate the LuproLoc ® safety device by pushing the arrow on the lock upward towards the needle tip with the thumb or finger, as illustrated, until the needle cover of the safety device over the needle is fully extended and a click is heard or felt (see Figure G ).
Figure G: 10.
Dispose of the syringe according to local regulations/procedures.