Use aseptic technique throughout the procedure.  As with other similar agents, the use of gloves is recommended during mixing and administration.¹  Allow the product to reach room temperature before mixing.  Once mixed, the product must be administered within 30 minutes or it should be discarded.

• ELIGARD^® is packaged in a carton containing two thermoformed trays and this package insert:

Table 2:   Contents of the Two Trays in the ELIGARD^® Carton

Syringe A Tray	Syringe B Tray
Syringe A pre-filled with the ATRIGEL® Delivery System	Syringe B pre-filled with the leuprolide acetate powder
Long white plunger rod	Safety needle
Desiccant pack	Desiccant pack

Follow the detailed instructions below to ensure correct preparation of ELIGARD^® prior to administration:

Figure 1-1 Figure 1-2	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.
Figure 2	2. Pull out (do not unscrew) the short blue plunger rod with attached gray stopper from Syringe B and discard.
Figure 3	3. Gently screw the white plunger rod into the remaining gray stopper in Syringe B.
Figure 4	4. Unscrew and discard the clear cap from Syringe A.
Figure-5	5. Remove and discard the gray rubber cap from Syringe B.
Figure-6	6. Join the two syringes together by pushing and gently screwing until secure.
Figure-7	7. Inject the liquid contents of Syringe A into the leuprolide acetate powder contained in Syringe B. Thoroughly mix the product for approximately 45 seconds by pushing the contents back and forth between both syringes to obtain a uniform suspension. When thoroughly mixed, the suspension will appear light tan to tan (ELIGARD® 7.5 mg) or colorless to pale yellow (ELIGARD® 22.5 mg, 30 mg and 45 mg). Note: Product must be mixed as described; shaking will NOT provide adequate mixing.
Figure-8	8. After mixing, hold the syringes vertically (upright) with Syringe B (short, wide syringe) on the bottom. The syringes should remain securely coupled. Draw all of the mixed product into Syringe B by depressing the Syringe A plunger and slightly withdrawing the Syringe B plunger.
Figure-9	9. Unscrew Syringe A to decouple the syringes while continuing to push down on the Syringe A plunger. Note: Small air bubbles will remain in the formulation – this is acceptable.
step 10	10. Continue to hold Syringe B upright with the open end at the top. Hold back the white plunger on Syringe B to prevent loss of the product and attach the safety needle cartridge. Gently screw clockwise with approximately a three-quarter turn until the needle is secure. Do not overtighten, as the hub may become damaged resulting in leakage of the product during injection. The safety sheath may also be damaged if the needle is screwed with too much force.
Figure11	11. (1) Move the safety sheath away from the needle and towards the syringe and (2) pull off the clear needle cartridge cover immediately prior to administration.

Note: Should the needle hub appear to be damaged, or leak, the product should NOT be used. The damaged needle should NOT be replaced and the product should NOT be injected. In the event of damage to the needle hub, use a new replacement ELIGARD^® carton.

Figure 2-2-1	1. Select an injection site on the abdomen, upper buttocks, or another location with adequate amounts of subcutaneous tissue that does not have excessive pigment, nodules, lesions, or hair and hasn’t recently been used. 2. Cleanse the injection-site area with an alcohol swab (not enclosed). 3. Using the thumb and forefinger, grab and bunch the area of skin around the injection site.
Figure 2-2-2	4. Using your dominant hand, insert the needle quickly at a 90° angle to the skin surface. The depth of penetration will depend on the amount and fullness of the subcutaneous tissue and the length of the needle. After the needle is inserted, release the skin. 5. Inject the drug using a slow, steady push and press down on the plunger until the syringe is empty. 6. Withdraw the needle quickly at the same 90° angle used for insertion.
Figure-7 Figure 7-2	7. Immediately following the withdrawal of the needle, activate the safety shield using a finger/thumb or flat surface and push until it completely covers the needle tip and locks into place.
Figure-2-8-8 Figure 2-8-9	8. An audible and tactile “click” verifies a locked position. 9. Check to confirm the safety sheath is fully engaged. Discard all components safely in an appropriate biohazard container.

ELIGARD^® 7.5 mg 22.5 mg 30 mg, like other GnRH agonists, causes a transient increase in serum concentrations of testosterone during the first week of treatment. ELIGARD^® 45 mg causes a transient increase in serum concentrations of testosterone during the first two weeks of treatment.  Patients may experience worsening of symptoms or onset of new signs and symptoms during the first few weeks of treatment, including bone pain, neuropathy, hematuria, or bladder outlet obstruction.

Cases of ureteral obstruction and/or spinal cord compression, which may contribute to paralysis with or without fatal complications, have been observed in the palliative treatment of advanced prostate cancer using GnRH agonists.

Patients with metastatic vertebral lesions and/or with urinary tract obstruction should be closely observed during the first few weeks of therapy. If spinal cord compression or ureteral obstruction develops, standard treatment of these complications should be instituted.

Response to ELIGARD^® should be monitored by periodic measurement of serum concentrations of testosterone and prostate specific antigen.

In the majority of patients, testosterone levels increased above Baseline during the first week, declining thereafter to Baseline levels or below by the end of the second or third week.  Castrate levels were generally reached within two to four weeks.

Castrate testosterone levels were maintained for the duration of the treatment with ELIGARD^® 7.5 mg.  No increases to above the castrate level occurred in any of the patients.

Castrate levels were generally maintained for the duration of treatment with ELIGARD^® 22.5 mg.

Once castrate levels were achieved with ELIGARD^® 30 mg, most (86/89) patients remained suppressed throughout the study.

Once castrate levels were achieved with ELIGARD^® 45 mg, only one patient (< 1%) experienced a breakthrough, with testosterone levels > 50 ng/dL.

Results of testosterone determinations are dependent on assay methodology.  It is advisable to be aware of the type and precision of the assay methodology to make appropriate clinical and therapeutic decisions.

Drug/Laboratory Test Interactions:  Therapy with leuprolide acetate results in suppression of the pituitary-gonadal system.  Results of diagnostic tests of pituitary gonadotropic and gonadal functions conducted during and after leuprolide therapy may be affected.

Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Hyperglycemia may represent development of diabetes mellitus or worsening of glycemic control in patients with diabetes. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with current practice for treatment of hyperglycemia or diabetes.

Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists in men. The risk appears low based on the reported odds ratios, and should be evaluated carefully along with cardiovascular risk factors when determining a treatment for patients with prostate cancer. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice.

Androgen deprivation therapy may prolong the QT/QTc interval. Providers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes.

Based on findings in animal studies and mechanism of action, leuprolide acetate may cause fetal harm when administered to a pregnant woman. In animal developmental and reproductive studies, major fetal abnormalities were observed after administration of leuprolide acetate throughout gestation in rats. Advise pregnant patients and females of reproductive potential of the potential risk to the fetus [see Use in Specific Populations (8.1), Clinical Pharmacology (12.1)].

Postmarketing reports of convulsions have been observed in patients on leuprolide acetate therapy. These included patients with 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 such as bupropion and SSRIs. Convulsions have also been reported in patients in the absence of any of the conditions mentioned above. Patients receiving a GnRH agonist who experience convulsion should be managed according to current clinical practice.

The safety of all ELIGARD^® formulations was evaluated in clinical trials involving patients with advanced prostate cancer.  In addition, the safety of ELIGARD^® 7.5 mg was evaluated in 8 surgically castrated males (Table 5).  ELIGARD^®, like other GnRH analogs, caused a transient increase in serum testosterone concentrations during the first one to two weeks of treatment.  Therefore, potential exacerbations of signs and symptoms of the disease during the first weeks of treatment are of concern in patients with vertebral metastases and/or urinary obstruction or hematuria.  If these conditions are aggravated, it may lead to neurological problems such as weakness and/or paresthesia of the lower limbs or worsening of urinary symptoms [see WARNINGS AND PRECAUTIONS (5.2)].

During the clinical trials, injection sites were closely monitored.  Refer to Table 4 for a summary of reported injection site events.

Table 4. Reported Injection Site Adverse Events

ELIGARD®	7.5 mg	22.5 mg	30 mg	45 mg
Study number	AGL9904	AGL9909	AGL0001	AGL0205
Number of patients	120	117	90	111
Treatment	1 injection every month up to 6 months	1 injection every 3 months up to 6 months	1 injection every 4 months up to 8 months	1 injection every 6 months up to 12 months
Number of injections	716	230	175	217
Transient burning/ stinging	248 (34.6%) injections; 84% reported as mild	50 (21.7%) injections; 86% reported as mild	35 (20%) injections; 100% reported as mild	35 (16%) injections; 91.4% reported as mild3
Pain (generally brief and mild)	4.3% of injections (18.3% of patients)	3.5% of injections (6.0% of patients)	2.3% of injections2 (3.3% of patients)	4.6% of injections4
Erythema (generally brief and mild)	2.6% of injections (12.5% of patients)	0.9% of injections1 (1.7% of patients)	1.1% of injections (2.2% of patients)	-
Bruising (mild)	2.5% of injections (11.7% of patients)	1.7% of injections (3.4% of patients)	-	2.3% of injections5
Pruritus	1.4% of injections (9.2% of patients)	0.4% of injections (0.9% of patients)	-	-
Induration	0.4% of injections (2.5% of patients)	-	-	-
Ulceration	0.1% of injections (> 0.8% of patients)	-	-	-
Erythema was reported following 2 injections of ELIGARD® 22.5 mg. One report characterized the erythema as mild and it resolved within 7 days. The other report characterized the erythema as moderate and it resolved within 15 days. Neither patient experienced erythema at multiple injection times. A single event reported as moderate pain resolved within two minutes and all 3 mild pain events resolved within several days following injection of ELIGARD® 30 mg. Following injection of ELIGARD® 30 mg, three of the 35 burning/stinging events were reported as moderate. Transient pain was reported as mild in intensity in nine of ten (90%) events and moderate in intensity in one of ten (10%) events following injection of ELIGARD® 45 mg. Mild bruising was reported following 5 (2.3%) study injections and moderate bruising was reported following 2 (<1%) study injections of ELIGARD® 45 mg.

These localized adverse events were non-recurrent over time.  No patient discontinued therapy due to an injection site adverse event.

The following possibly or probably related systemic adverse events occurred during clinical trials with ELIGARD^®, and were reported in > 2% of patients (Table 5).  Often, causality is difficult to assess in patients with metastatic prostate cancer.  Reactions considered not drug-related are excluded.

Table 5. Summary of Possible or Probably Related Systemic Adverse Events Reported by > 2% of Patients Treated with ELIGARD^®

ELIGARD®				7.5 mg	7.5 mg	22.5 mg	30 mg	45 mg
Study number				AGL9904	AGL9802	AGL9909	AGL0001	AGL0205
Number of patients				120	8	117	90	111
Treatment				1 injection every month up to 6 months	1 injection (surgically castrated patients)	1 injection every 3 months up to 6 months	1 injection every 4 months up to 8 months	1 injection every 6 months up to 12 months
Body system			Adverse event	Number (percent)
Body as a whole			Malaise and fatigue	21 (17.5%)	-	7 (6.0%)	12 (13.3%)	13 (11.7%)
			Weakness	-	-	-	-	4 (3.6%)
Nervous system			Dizziness	4 (3.3%)	-	-	4 (4.4%)	-
Vascular			Hot flashes/sweats	68 (56.7%)*	2 (25.0%)*	66 (56.4%)*	66 (73.3%)*	64 (57.7%)*
Renal/urinary			Urinary frequency	-	-	3 (2.6%)	2 (2.2%)	-
			Nocturia	-	-	-	2 (2.2%)	-
Gastrointestinal			Nausea	-	-	4 (3.4%)	2 (2.2%)	-
			Gastroenteritis/colitis	3 (2.5%)	-	-	-	-
Skin			Pruritus	-	-	3 (2.6%)	-	-
			Clamminess	-	-	-	4 (4.4%)*	-
			Night sweats	-	-	-	3 (3.3%)*	3 (2.7%)*
			Alopecia	-	-	-	2 (2.2%)	-
Musculoskeletal			Arthralgia	-	-	4 (3.4%)	-	-
			Myalgia	-	-	-	2 (2.2%)	5 (4.5%)
			Pain in limb	-	-	-	-	3 (2.7%)
Reproductive			Testicular atrophy	6 (5.0%)	-	-	4 (4.4%)*	8 (7.2%)*
			Gynecomastia	-	-	-	2 (2.2%)*	4 (3.6%)*
			Testicular pain	-	-	-	2 (2.2%)	-
Psychiatric			Decreased libido	-	-	-	3 (3.3%)*	-
*Expected pharmacological consequences of testosterone suppression. In the patient populations studied with ELIGARD® 7.5 mg, a total of 86 hot flashes/sweats adverse events were reported in 70 patients. Of these, 71 events (83%) were mild; 14 (16%) were moderate; 1 (1%) was severe. In the patient population studied with ELIGARD® 22.5 mg, a total of 84 hot flashes/sweats adverse events were reported in 66 patients. Of these, 73 events (87%) were mild; 11 (13%) were moderate; none were severe. In the patient population studied with ELIGARD® 30 mg, a total of 75 hot flash adverse events were reported in 66 patients. Of these, 57 events (76%) were mild; 16 (21%) were moderate; 2 (3%) were severe. In the patient population studied with ELIGARD® 45 mg, a total of 89 hot flash adverse events were reported in 64 patients. Of these, 62 events (70%) were mild; 27 (30%) were moderate; none were severe.

In addition, the following possibly or probably related systemic adverse events were reported by < 2% of the patients treated with ELIGARD^® in these clinical studies.

Body system	Adverse event
General	Sweating, insomnia, syncope, rigors, weakness, lethargy
Gastrointestinal	Flatulence, constipation, dyspepsia
Hematologic	Decreased red blood cell count, hematocrit and hemoglobin
Metabolic	Weight gain
Musculoskeletal	Tremor, backache, joint pain, muscle atrophy, limb pain
Nervous	Disturbance of smell and taste, depression, vertigo
Psychiatric	Insomnia, depression, loss of libido*
Renal/urinary	Difficulties with urination, pain on urination, scanty urination, bladder spasm, blood in urine, urinary retention, urinary urgency, incontinence, nocturia, nocturia aggravated
Reproductive/ Urogenital	Testicular soreness/pain, impotence*, decreased libido*, gynecomastia*, breast soreness/tenderness*, testicular atrophy*, erectile dysfunction, penile disorder*, reduced penis size
Skin	Alopecia, clamminess, night sweats*, sweating increased*
Vascular	Hypertension, hypotension
* Expected pharmacological consequences of testosterone suppression.

Changes in Bone Density:  Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with a GnRH agonist analog.  It can be anticipated that long periods of medical castration in men will have effects on bone density.

Pituitary apoplexy-During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma was diagnosed with a majority of pituitary apoplexy cases occurring within 2 weeks of the first dose, and some within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required.

Nervous System-Convulsions

Respiratory System-Interstitial lung disease

Risk Summary
Based on findings in animal studies and mechanism of action, ELIGARD^® may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data in pregnant women to inform the drug-associated risk. Expected hormonal changes that occur with ELIGARD^® treatment increase the risk for pregnancy loss. In animal developmental and reproductive studies, major fetal abnormalities were observed after administration of leuprolide acetate throughout gestation in rats. Advise pregnant patients and females of reproductive potential of the potential risk to the fetus (see Data).

Animal Data
In animal developmental and reproductive studies, major fetal abnormalities were observed after administration of leuprolide acetate throughout gestation.  There were increased fetal mortality and decreased fetal weights in rats and rabbits.  The effects of fetal mortality are expected consequences of the alterations in hormonal levels brought about by this drug.

The safety and efficacy of ELIGARD^® have not been established in females. There is no information regarding the presence of ELIGARD^® in human milk, the effects on the breastfed child, or the effects on milk production. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in a breastfed child from ELIGARD^®, a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Infertility
Males
Based on mechanism of action, ELIGARD^® may impair fertility in males of reproductive potential  [see Clinical Pharmacology (12.1)].

The safety and effectiveness of ELIGARD^® in pediatric patients have not been established.

The majority of the patients (approximately 70%) studied in the clinical trials were age 70 and older.

Leuprolide acetate, a gonadotropin releasing hormone (GnRH) agonist, acts as a potent inhibitor of gonadotropin secretion when given continuously in therapeutic doses.  Animal and human studies indicate that after an initial stimulation, chronic administration of leuprolide acetate results in suppression of testicular and ovarian steroidogenesis.  This effect is reversible upon discontinuation of drug therapy.

In humans, administration of leuprolide acetate results in an initial increase in circulating levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), leading to a transient increase in levels of the gonadal steroids (testosterone and dihydrotestosterone in males, and estrone and estradiol in premenopausal females).  However, continuous administration of leuprolide acetate results in decreased levels of LH and FSH.  In males, testosterone is reduced to below castrate threshold (≤50 ng/dL).  These decreases occur within two to four weeks after initiation of treatment.  Long-term studies have shown that continuation of therapy with leuprolide acetate maintains testosterone below the castrate level for up to seven years.

Following the first dose of ELIGARD^®, mean serum testosterone concentrations transiently increased, then fell to below castrate threshold (≤ 50 ng/dL) within three weeks for all ELIGARD^® concentrations.

Continued monthly treatment with ELIGARD^® 7.5 mg maintained castrate testosterone suppression throughout the study.  No breakthrough of testosterone concentrations above castrate threshold (> 50 ng/dL) occurred at any time during the study once castrate suppression was achieved (Figure 1).

One patient received less than a full dose of ELIGARD^® 22.5 mg at baseline, never suppressed and withdrew from the study at Day 73.  Of the 116 patients remaining in the study, 115 (99%) had serum testosterone levels below the castrate threshold by Month 1 (Day 28).  By Day 35, 116 (100%) had serum testosterone levels below the castrate threshold.  Once testosterone suppression was achieved, one patient (< 1%) demonstrated breakthrough (concentrations > 50 ng/dL after achieving castrate levels) following the initial injection; that patient remained below the castrate threshold following the second injection (Figure 2).

One patient withdrew from the ELIGARD^® 30 mg study at Day 14.  Of the 89 patients remaining in the study, 85 (96%) had serum testosterone levels below the castrate threshold by Month 1 (Day 28).  By Day 42, 89 (100%) of patients attained castrate testosterone suppression.  Once castrate testosterone suppression was achieved, three patients (3%) demonstrated breakthrough (concentrations > 50 ng/dL after achieving castrate levels) (Figure 3).

One patient at Day 1 and another patient at Day 29 were withdrawn from the ELIGARD^® 45 mg study.  Of the 109 patients remaining in the study, 108 (99.1%) had serum testosterone levels below the castrate threshold by Month 1 (Day 28).  One patient did not achieve castrate suppression and was withdrawn from the study at Day 85.  Once castrate testosterone suppression was achieved, one patient (< 1%) demonstrated breakthrough (concentrations > 50 ng/dL after achieving castrate levels) (Figure 4).

Leuprolide acetate is not active when given orally.

Absorption

ELIGARD^® 7.5 mg
The pharmacokinetics/pharmacodynamics observed during three once-monthly injections in 20 patients with advanced prostate cancer is shown in Figure 1.  Mean serum leuprolide concentrations following the initial injection rose to 25.3 ng/mL (C_max) at approximately 5 hours after injection.  After the initial increase following each injection, serum concentrations remained relatively constant (0.28 – 2.00 ng/mL).

Figure 1. Pharmacokinetic/Pharmacodynamic Response (N=20) to ELIGARD^® 7.5 mg – Patients Dosed Initially and at Months 1 and 2

A reduced number of sampling time points resulted in the apparent decrease in C_max values with the second and third doses of ELIGARD^® 7.5 mg (Figure 1).

ELIGARD^® 22.5 mg
The pharmacokinetics/pharmacodynamics observed during two injections every three months (ELIGARD^® 22.5 mg) in 22 patients with advanced prostate cancer is shown in Figure 2.  Mean serum leuprolide concentrations rose to 127 ng/mL and 107 ng/mL at approximately 5 hours following the initial and second injections, respectively.  After the initial increase following each injection, serum concentrations remained relatively constant (0.2 – 2.0 ng/mL).

Figure 2.  Pharmacokinetic/Pharmacodynamic Response (N=22) to ELIGARD^® 22.5 mg – Patients Dosed Initially and at Month 3

ELIGARD^® 30 mg
The pharmacokinetics/pharmacodynamics observed during injections administered initially and at four months (ELIGARD^® 30 mg) in 24 patients with advanced prostate cancer is shown in Figure 3.  Mean serum leuprolide concentrations following the initial injection rose rapidly to 150 ng/mL (C_max) at approximately 3.3 hours after injection.  After the initial increase following each injection, mean serum concentrations remained relatively constant (0.1 – 1.0 ng/mL).

Figure 3. Pharmacokinetic/Pharmacodynamic Response (N=24) to ELIGARD^® 30 mg - Patients Dosed Initially and at Month 4

ELIGARD^® 45 mg
The pharmacokinetics/pharmacodynamics observed during injections administered initially and at six months (ELIGARD^® 45 mg) in 27 patients with advanced prostate cancer is shown in Figure 4.  Mean serum leuprolide concentrations rose to 82 ng/mL and 102 ng/mL (C_max) at approximately 4.5 hours following the initial and second injections, respectively. After the initial increase following each injection, mean serum concentrations remained relatively constant (0.2 – 2.0 ng/mL).

Figure 4. Pharmacokinetic/Pharmacodynamic Response (N=27) to ELIGARD^® 45 mg - Patients Dosed Initially and at Month 6

 

There was no evidence of significant accumulation during repeated dosing.  Non-detectable leuprolide plasma concentrations have been occasionally observed during ELIGARD^® administration, but testosterone levels were maintained at castrate levels.

Distribution.  The mean steady-state volume of distribution of leuprolide following intravenous bolus administration to healthy male volunteers was 27 L. In vitro binding to human plasma proteins ranged from 43% to 49%.

Metabolism.  In healthy male volunteers, a 1-mg bolus of leuprolide administered intravenously revealed that the mean systemic clearance was 8.34 L/h, with a terminal elimination half-life of approximately 3 hours based on a two compartment model.

No drug metabolism study was conducted with ELIGARD^®.  Upon administration with different leuprolide acetate formulations, the major metabolite of leuprolide acetate is a pentapeptide (M-1) metabolite.

Excretion.  No drug excretion study was conducted with ELIGARD^®.

Geriatrics. [see USE IN SPECIAL POPULATIONS (8.5)]

Race.  In patients studied, mean serum leuprolide concentrations were similar regardless of race.  Refer to Table 7 for distribution of study patients by race.

Table 7.  Race Characterization of ELIGARD^® Study Patients

Race	ELIGARD® 7.5 mg	ELIGARD® 22.5 mg	ELIGARD® 30 mg	ELIGARD® 45 mg
White	26	19	18	17
Black	-	4	4	7
Hispanic	2	2	2	3

Renal and Hepatic Insufficiency.  The pharmacokinetics of ELIGARD^® in hepatically and renally impaired patients have not been determined.

Two-year carcinogenicity studies were conducted with leuprolide acetate in rats and mice.  In rats, a dose-related increase of benign pituitary hyperplasia and benign pituitary adenomas was noted at 24 months when the drug was administered subcutaneously at high daily doses (0.6 to 4 mg/kg).  There was a significant but not dose-related increase of pancreatic islet-cell adenomas in females and of testicular interstitial cell adenomas in males (highest incidence in the low dose group).  In mice, no leuprolide acetate-induced tumors or pituitary abnormalities were observed at a dose as high as 60 mg/kg for two years. Patients have been treated with leuprolide acetate for up to three years with doses as high as 10 mg/day and for two years with doses as high as 20 mg/day without demonstrable pituitary abnormalities. No carcinogenicity studies have been conducted with ELIGARD ^® .

Mutagenicity studies have been performed with leuprolide acetate using bacterial and mammalian systems and with ELIGARD ^®  7.5 mg in bacterial systems.  These studies provided no evidence of a mutagenic potential.

ELIGARD^® is available in a single-dose kit of a two syringe-mixing system with a sterile safety needle in the following strengths:

ELIGARD^® 7.5 mg – NDC 62935-753-75
ELIGARD^® 22.5 mg – NDC 62935-223-05
ELIGARD^® 30 mg – NDC 62935-303-30
ELIGARD^® 45 mg – NDC 62935-453-45

Store 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 mixing and administration.