Eligard

Name: Eligard

Notes

Do not share this medication with others.Laboratory and/or medical tests (e.g., blood testosterone level, PSA blood test, blood glucose) should be performed periodically to monitor your progress. Consult your doctor for more details.

How supplied

Dosage Forms And Strengths

ELIGARD®  is an injectable suspension of leuprolide acetate available in a single use kit. The kit consists of a two-syringe mixing system, a sterile needle or a sterile safety needle (Table 2), a silica gel desiccant pouch to control moisture uptake, and a package insert for constitution and administration procedures. Each syringe is individually packaged. One contains the ATRIGEL Delivery System and the other contains leuprolide acetate powder. When constituted, ELIGARD®  is administered as a single dose.

Table 2: ELIGARD®  Needle specifications

ELIGARD® formulation Sterile needle Sterile safety needle
Gauge Length Gauge Length
7.5 mg 20-gauge ½-inch 20- gauge 5/8-inch
22.5 mg 20-gauge ½-inch gauge 5/8-inch
30 mg 20-gauge 5/8-inch 20- gauge 5/8-inch
45 mg 18-gauge 5/8-inch 18- gauge 5/8-inch

Storage And Handling

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

ELIGARD®  7.5 mg – NDC 62935-752-75
ELIGARD®  22.5 mg – NDC 62935-222-05
ELIGARD®  30 mg – NDC 62935-302-30
ELIGARD®  45 mg – NDC 62935-452-45

ELIGARD®  is available in a single use 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

Storage

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.

Manufactured by: TOLMAR Inc., Fort Collins, CO 80526. for: TOLMAR Therapeutics, Inc. Fort Collins, CO 80526. Distributed by: TOLMAR Pharmaceuticals, Inc., Fort Collins, CO 80526. Revised: Feb 2016

Side effects

Clinical Trial Experience

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 4). 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].

During the clinical trials, injection sites were closely monitored. Refer to Table 3 for a summary of reported injection site events.

Table 3: Reported Injection Site Advers e 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/s tinging 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)  
Druisuig (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)      
1. 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 injections.
2. 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.
3. Following injection of ELIGARD®  30 mg, three of the 35 burning/stinging events were reported as moderate.
4. 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.
5. 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 4). Often, causality is difficult to assess in patients with metastatic prostate cancer. Reactions considered not drug-related are excluded.

Table 4: 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 mo nths 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 mo nths up to 12 mo nths
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
Nervous system Dizziness 4 (3.3%)     4 (4.4%) 4 (3.6%)
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%)        
  Pruritus     3 (2.6%)    
Skin Clamminess       4 (4.4%)*  
Night sweats       3 (3.3%)* 3 (2.7%)*
  Alopecia       2 (2.2%)  
  Arthralgia     4 (3.4%)  
Musculoskeletal 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.

Postmarketing Experience

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.

Convulsions have also been reported in the postmarketing setting.

Clinical pharmacology

Mechanism Of Action

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.

Pharmacodynamics

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 18).

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 19).

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 20).

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 21).

Leuprolide acetate is not active when given orally.

Pharmacokinetics

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 18. Mean serum leuprolide concentrations following the initial injection rose to 25.3 ng/mL (Cmax ) 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 18: 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 Cmax values with the second and third doses of ELIGARD®  7.5 mg (Figure 18).

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 19. 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 19: Pharmacokinetic/Pharmacodynamic Res ponse (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 20. Mean serum leuprolide concentrations following the initial injection rose rapidly to 150 ng/mL (Cmax ) 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 20: 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 21. Mean serum leuprolide concentrations rose to 82 ng/mL and 102 ng/mL (C ) 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 21: 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]

Race

In patients studied, mean serum leuprolide concentrations were similar regardless of race. Refer to Table 6 for distribution of study patients by race.

Table 6: 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.

Clinical Studies

One open-label, multicenter study was conducted with each ELIGARD®  formulation (7.5 mg, 22.5 mg, 30 mg, and 45 mg) in patients with Jewett stage A though D prostate cancer who were treated with at least a single injection of study drug (Table 7). These studies evaluated the achievement and maintenance of castrate serum testosterone suppression over the duration of therapy (Figures 22-25).

During the AGL9904 study using ELIGARD®  7.5 mg, once testosterone suppression was achieved, no patients (0%) demonstrated breakthrough (concentration > 50 ng/dL) at any time in the study.

During the AGL9909 study using ELIGARD®  22.5 mg, once testosterone suppression was achieved, only one patient ( < 1%) demonstrated breakthrough following the initial injection; that patient remained below the castrate threshold following the second injection.

During the AGL0001 study using ELIGARD®  30 mg, once testosterone suppression was achieved, three patients (3%) demonstrated breakthrough. In the first of these patients, a single serum testosterone concentration of 53 ng/dL was reported on the day after the second injection. In this patient, castrate suppression was reported for all other time points. In the second patient, a serum testosterone concentration of 66 ng/dL was reported immediately prior to the second injection. This rose to a maximum concentration of 147 ng/dL on the second day after the second injection. In this patient, castrate suppression was again reached on the seventh day after the second injection and was maintained thereafter. In the final patient, serum testosterone concentrations > 50 ng/dL were reported at 2 and at 8 hours after the second injection. Serum testosterone concentration rose to a maximum of 110 ng/dL on the third day after the second injection. In this patient, castrate suppression was again reached eighteen days after the second injection and was maintained until the final day of the study, when a single serum testosterone concentration of 55 ng/dL was reported.

During the AGL0205 study using ELIGARD®  45 mg, once testosterone suppression was achieved, one patient ( < 1%) demonstrated breakthrough. This patient reached castrate suppression at Day 21 and remained suppressed until Day 308 when his testosterone level rose to 112 ng/dL. At Month 12 (Day 336), his testosterone was 210 ng/dL.

Table 7: Summary of ELIGARD®Â  Clinical Studies

ELIGARD® 7.5 mg 22.5 mg 30 mg 45 mg
Study number AGL9904 AGL9909 AGL0001 AGL0205
Total number of patients 120 (117 completed) 1172 (111 completed3) 90 (82 completed4) 111 (103 completed5)
Jewett stages Stage A 2 2 5
Stage B 19 38 43
Stage C 89 60 16 19
Stage D 31 36 34 44
Treatment 6 monthly injections 1 injection (4 patients) 1 injection (5 patients) 1 injection (5 patients)
2 injections, one every three months (113 patients) 2 injections, one every four months (85 patients) 2 injections, o ne every six months (106 patients)
Duration of therapy 6 months 6 months 8 months 12 months
Mean testosterone concentration (ng/dL) Baseline 361.3 367.1 385.5 367.7
Day 2 574.6 (Day 3) 588.0 610.0 588.6
Day 14 Below Baseline (Day 10) Below Baseline Below Baseline Below Baseline
Day 28 21.8 27.7 (Day 21) 17.2 16.7
Conclusion 6.1 10.1 12.4 12.6
Number of patients below castrate threshold ( ≤ 50 ng/dL) Day 28 112 of 119 (94.1%) 115 of 116 (99%) 85 of 89 (96%) 108 of 109 (99.1%)
Day 35 116 (100%)
Day 42 119 (100%) 89 (100%)
Conclusion 1171 (100%) 111 (100%) 81 (99%) 102 (99%)
1. Two patients withdrew for reasons unrelated to drug.
2. One patient received less than a full dose at Baseline, never suppressed, and was withdrawn at Day 73 and given an alternate treatment.
3. All non-evaluable patients who attained castration by Day 28 maintained castration at each time point up to and including the time of withdrawal.
4. One patient withdrew on Day 14. All 7 non-evaluable patients who had achieved castration by Day 28 maintained castration at each time point, up to and including the time of withdrawal.
5. Two patients were withdrawn prior to the Month 1 blood draw. One patient did not achieve castration and was withdrawn on Day 85. All 5 non-evaluable patients who attained castration by Day 28, maintained castration at each time point up to and including the time of withdrawal.

Figure 22: ELIGARD®  7.5 mg Mean Serum Testosterone Concentrations (n=117)

Figure 23: ELIGARD®  22.5 mg Mean Serum Testosterone Concentrations (n=111)

Figure 24: ELIGARD®  30 mg Mean Serum Testosterone Concentrations (n=90)

Figure 25: ELIGARD®  45 mg Mean Serum Testosterone Concentrations (n=103)

Serum PSA decreased in all patients in all studies whose Baseline values were elevated above the normal limit. Refer to Table 8 for a summary of the effectiveness of ELIGARD®  in reducing serum PSA values.

Table 8: Effect of ELIGARD®  on Patient Serum PSA Values

ELIGARD® 7.5 mg 22.5 mg 30 mg 45 mg
Mean PSA reduction at study conclusion 94% 98% 86% 97%
Patients with normal PSA at study conclusion* 94% 91% 93% 95%
*Among patients who presented with elevated levels at Baseline

Other secondary efficacy endpoints evaluated included WHO performance status, bone pain, urinary pain and urinary signs and symptoms. Refer to Table 9 for a summary of these endpoints.

Table 9: Secondary Efficacy Endpoints

ELIGARD® 7.5 mg 22.5 mg 30 mg 45 mg
Baseline WHO Status = 01 88% 94% 90% 90%
WHO Status = 12 11% 6% 10% 7%
WHO Status = 23 - - - 3%
Mean bone pain4 (range) 1.22 (1-9) 1.20 (1-9) 1.20 (1-7) 1.38 (1-7)
Mean urinary pain (range) 1.12 (1-5) 1.02 (1-2) 1.01 (1-2) 1.22 (1-8)
Mean urinary signs and symptoms (range) Low 1.09 (1-4) Low Low
Number of patients with prostate abnormalities 102 (85%) 96 (82%) 66 (73%) 89 (80%)
    Month 6 Month 6 Month 8 Month 12
Follow- up WHO status = 0 Unchanged 96% 87% 94%
WHO status = 1 Unchanged 4% 12% 5%
WHO status = 2 - - 1% 1%
Mean bone pain (range) 1.26 (1-7) 1.22 (1-5) 1.19 (1-8) 1.31 (1-8)
  Mean urinary pain (range) 1.07 (1-8) 1.10 (1-8) 1.00 (1-1) 1.07 (1-5)
Mean urinary signs and symptoms (range) Modestly decreased 1.18 (1-7) Modestly decreased Modestly decreased
Number of patients with prostate abnormalities 77 (64%) 76 (65%) 54 (60%) 60 (58%)
1. WHO status = 0 classified as “fully active.”
2. WHO status = 1 classified as “restricted in strenuous activity but ambulatory and able to carry out work of a light or sedentary nature.”
3. WHO status = 2 classified as “ambulatory but unable to carry out work activities.”
4. Pain score scale: 1 (no pain) to 10 (worst pain possible).

REFERENCES

1. “OSHA Hazardous Drugs.” OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

Uses of Eligard

Eligard is a prescription hormone medication used to treat advanced prostate cancer.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Manufacturer

  • Sanofi-Aventis U.S. LLC

  • TOLMAR Inc.

Eligard Interactions

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

  • amiodarone (Cordarone, Pacerone)
  • bupropion (Zyban, Wellbutrin)
  • dexamethasone (Decadron)
  • disopyramide (Norpace)
  • methylprednisolone (Medrol)
  • prednisone (Deltasone)
  • procainamide (Procanbid)
  • quinidine
  • sotalol (Betapace)
  • seizure medications
  • selective serotonin reuptake inhibitors (SSRIs) such as escitalopram (Lexapro), sertraline (Zoloft), citalopram (Celexa), vilazodone (Viibryd), paroxetine (Paxil), fluoxetine (Prozac, Sarafem, Symbyax), and fluvoxamine (Luvox)

This is not a complete list of Eligard drug interactions. Ask your doctor or pharmacist for more information.

Eligard Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

For adultsLess common
  • Fast or irregular heartbeat
Rare
  • Bone, muscle, or joint pain
  • fainting
  • fast or irregular breathing
  • numbness or tingling of the hands or feet
  • puffiness or swelling of the eyelids or around the eyes
  • skin rash, hives, or itching
  • sudden, severe decrease in blood pressure and collapse
  • tightness in the chest
  • troubled breathing
For males only (adults)More common
  • Arm, back, or jaw pain
  • bloody or cloudy urine
  • blurred vision
  • chest pain or discomfort
  • difficult, burning, or painful urination
  • difficulty with moving
  • dizziness
  • frequent urge to urinate
  • headache
  • increased urge to urinate during the night
  • muscle pain or stiffness
  • nausea
  • nervousness
  • pain in the joints
  • pale skin
  • pounding in the ears
  • slow or fast heartbeat
  • sweating
  • troubled breathing with exertion
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • waking to urinate at night
Rare
  • Pain in the groin or legs (especially in the calves)
Incidence not known
  • Altered mental status
  • cardiovascular collapse
  • double vision
  • visual changes
  • vomiting
For females only (adults)Rare
  • Anxiety
  • deepening of voice
  • increased hair growth
  • mental depression
  • mood changes
For childrenRare
  • Body pain
  • burning, itching, redness, or swelling at the injection site
For females only (children)—expected in first few weeksRare
  • Vaginal bleeding (continuing)
  • white vaginal discharge (continuing)

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

For adultsMore common
  • Sudden sweating and feelings of warmth (hot flashes)
Less common
  • Bleeding, bruising, burning, itching, pain, redness, or swelling at the injection site
  • decreased interest in sexual intercourse
  • swelling of the feet or lower legs
  • swelling or increased tenderness of the breasts
  • trouble sleeping
  • weight gain
For females only (adults)More common
  • Light, irregular vaginal bleeding
  • stopping of menstrual periods
Less common
  • Burning, dryness, or itching of the vagina
  • pelvic pain
For males only (adults)More common
  • Back pain
  • chills
  • constipation
  • cough
  • diarrhea
  • fever
  • general feeling of discomfort or illness
  • loss of appetite
  • pain or discomfort at the injection site
  • redness of the face, neck, arms, and occasionally, upper chest
  • runny nose
  • shivering
  • sore throat
  • unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
Less common
  • Decreased size of the testicles
  • inability to have or keep an erection

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Adverse reactions

6.1 Clinical Trial Experience

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 4).  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 3 for a summary of reported injection site events.

Table 3. 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)
 -  -  -
  1. 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.
  2. 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.
  3. Following injection of Eligard® 30 mg, three of the 35 burning/stinging events were reported as moderate.
  4. 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.
  5. 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 4).  Often, causality is difficult to assess in patients with metastatic prostate cancer.  Reactions considered not drug-related are excluded.

Table 4. 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.

6.2 Post-marketing Experience

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.

Convulsions have also been reported in the postmarketing setting.

What other drugs will affect Eligard?

Eligard can cause a serious heart problem, especially if you use certain medicines at the same time, such as antibiotics, antifungal medicine, antidepressants, anti-malaria medicine, asthma inhalers, antipsychotic medicine, cancer medicine, certain HIV/AIDS medicine, heart or blood pressure medicine, or medicine to prevent vomiting. Tell your doctor about all your current medicines and any medicine you start or stop using.

Other drugs may interact with leuprolide, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Leuprolide Breastfeeding Warnings

Use is contraindicated. Excreted into human milk: Unknown Excreted into animal milk: Data not available Comments: The effects in the nursing infant are unknown.

What other drugs will affect leuprolide?

Leuprolide can cause a serious heart problem, especially if you use certain medicines at the same time, such as antibiotics, antifungal medicine, antidepressants, anti-malaria medicine, asthma inhalers, antipsychotic medicine, cancer medicine, certain HIV/AIDS medicine, heart or blood pressure medicine, or medicine to prevent vomiting. Tell your doctor about all your current medicines and any medicine you start or stop using.

Other drugs may interact with leuprolide, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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